Clinical trials

As our Canadian population ages, hip fractures in these older adults are becoming very common. The best treatment for the majority of these injuries is urgent treatment with surgery. However, the hip fracture itself, the surgery required, and the immobility following these injuries are all risk factors for developing blood clots in the legs (deep vein thrombosis or DVT) and blood clots in the lungs (pulmonary embolism or PE). These complications are a common cause of death in patients with hip fractures and often result in prolonged medical treatment and hospital stays. Patients with hip fractures who require surgery are traditionally given injectable blood thinners to help prevent blood clots; however, these medications are costly, may not be tolerated well, and can be difficult to take, as prescribed. Oral blood thinning medications are being used more commonly, but it is unknown which of these medications is the most effective in preventing blood clots in patients after a hip fracture. Thrombelastography (TEG) technology uses a small sample of blood to evaluate a person's clotting ability. Our research has used TEG technology to evaluate blood clotting risk after hip fracture surgery and the investigators have found that platelets may play an important role in abnormal blood clotting after a hip fracture. The investigators have also shown that acetylsalicylic acid (ASA or Aspirin) may help reduce the abnormal platelet hyperactivity associated with blood clotting. This medication warrants investigation for blood clot prevention after hip fracture. The investigators propose to directly compare different oral medication regimens after hip fracture surgery, in order to determine which is safest and most effective in preventing blood clots. Our multi-disciplinary research team includes physicians, surgeons, and scientists with experience evaluating different medications for blood clot prevention. Our results will help determine the best medical treatment for preventing DVT and PE, which will benefit patients with hip fractures worldwide.

Fragility fractures are common in older adults with weakened bone. At least 1 in 3 females and 1 in 5 males will sustain a fragility fracture in their lifetime, and over 80% of fractures in Canadians aged 50 years and older are attributable to osteoporosis. Fractures of the pelvis, acetabulum and lower extremity in this population are associated with delayed healing, loss of reduction, implant failure and the need for secondary surgery. Reported complication rates range from 21.5% to 40%. Efforts to improve outcomes have focused on surgical fixation technique; there is currently no pharmacological treatment given to promote healing of the fracture itself. Teriparatide is a recombinant form of parathyroid hormone (1-34) that stimulates new bone formation. It is authorized in Canada for the treatment of severe osteoporosis. Its use to promote acute fracture healing is investigational and is not an approved indication. Pre-clinical studies have demonstrated enhanced fracture callus formation and improved mechanical strength of healing bone. Clinical evidence in acute fracture healing is limited and mixed: a randomized trial in distal radius fractures reported a shorter time to cortical bridging, and systematic reviews report positive signals in delayed union and non-union, while a small phase 2 trial in acute pelvic fracture found no difference in radiographic healing at three months, although physical performance improved. That trial was terminated early following withdrawal of study drug supply, leaving it underpowered, and its authors concluded that a larger randomized trial is warranted. No randomized controlled trial has evaluated Teriparatide for the promotion of fracture healing across pelvic, acetabular and non-hip lower extremity fragility fractures in high-risk older adults. Before such a trial can be designed and appropriately powered, its feasibility must be established. PRO HEAL Pilot is a prospective, open-label, randomized controlled pilot trial with blinded outcome assessment. Fifty-four participants will be randomized 1:1 to Teriparatide or a no-treatment control. Recruitment is planned over 18 months at the Foothills Medical Centre in Calgary. Eligible participants are males and females aged 50 years and older who have sustained a low-energy fragility fracture (a fall from five feet or less) of the pelvis, the acetabulum, or the non-hip lower extremity, and who have at least one additional risk factor for delayed fracture healing: diabetes, renal dysfunction, steroid use, current or past smoking, peripheral neuropathy, or peripheral vascular disease. Fractures may be managed operatively or non-operatively. Participants must be able and willing to self-administer daily subcutaneous injections, or have a caregiver able to do so. Participants randomized to the treatment arm receive Teriparatide 20 mcg by subcutaneous injection once daily for 90 doses, with the first dose administered within five days of randomization and within 21 days of the initial fracture. Participants randomized to the control arm receive no study medication and continue standard clinical care. All participants in both arms receive a single oral loading dose of 50,000 IU vitamin D at randomization, with calcium supplementation or dietary modification to achieve a total daily intake of approximately 1,000 mg. The primary outcome is feasibility, measured as the mean number of participants recruited per month and assessed against a priori progression criteria. Secondary feasibility outcomes are treatment fidelity, defined as the proportion of participants receiving 80% or more of the trial medication; participant retention; consent rate; and barriers to trial implementation. Clinical, functional and value-based outcomes will be collected in the same manner as planned for the full-scale trial and reported descriptively. Clinical outcomes include pain, radiographic fracture union, unplanned surgical intervention related to the index fracture, bone mineral density, and 90-day all-cause mortality. Functional outcomes include physical performance, the Olerud Molander Score, PROMIS Mobility, and weightbearing status. Value-based outcomes include healthcare costs, quality of life, length of acute hospital stay, and re-admission. Participants are followed for six months from randomization, with study visits at 2 weeks, 6 weeks, 12 weeks and 6 months, aligned with routine post-fracture clinical follow-up. Participants receiving Teriparatide are contacted weekly by telephone during the treatment period for adherence and safety monitoring, and serum calcium is measured at every study visit. Clinical outcomes are adjudicated by independent assessors blinded to treatment allocation. This pilot trial is not powered to detect a difference in clinical efficacy between treatment arms. Its purpose is to determine whether a definitive, full-scale randomized controlled trial is feasible, and to inform its design and sample size.

High blood pressure, also called hypertension, raises the risk of heart disease, stroke, and kidney disease. Medications work well for many people, but some people still have blood pressure that stays too high, or they have side effects from their medications. Researchers are looking for treatments that do not involve taking more medication. Nerves help control blood pressure by changing how blood vessels tighten and how hard the heart pumps. Because of this, treatments that act on nerves may be able to lower blood pressure. Spinal cord stimulation is a treatment already used to manage long-term pain. It uses a small device, placed under the skin during a standard operation, that sends mild electrical signals to the spine. Laboratory studies suggest that stimulating the lower part of the mid-back may also lower blood pressure, but this has not been carefully studied in people who already use these devices. This study will look at whether changing the settings on a spinal cord stimulator affects blood pressure. About 11 adults who have high blood pressure and who already have a spinal cord stimulator for long-term pain. No new device will be placed, and no surgery or other invasive procedure will be done for this study. Participants attend a series of study visits. At each visit, trained staff record blood pressure and heart rate while the stimulator is turned on, turned off, and set to other settings that the person's care team has approved and that the person finds comfortable. There are rest breaks between each setting. Over successive visits, the study team works to identify the settings that best lower blood pressure. Participants can stop at any time, and their usual settings are restored at the end of each visit. The study will also look at whether this kind of testing is practical and comfortable for participants. The results will help researchers decide whether larger studies of spinal cord stimulation for blood pressure control are worth doing.

Coronary artery disease, the narrowing of the blood vessels that supply the heart, is the leading cause of death worldwide. About 2.4 million Canadian adults live with it. There are three main ways to treat it: opening the narrowed artery with a stent, heart bypass surgery, or medications alone. For many patients the best choice is clear, but for people with complicated disease or multiple health conditions, it can be genuinely difficult to know which treatment will lead to the best outcome. For these complex cases, hospitals bring together a "heart team", a group of heart specialists including cardiologists and heart surgeons, to discuss the case and recommend the best treatment. Even so, studies show that different doctors, teams, and hospitals often make different decisions for similar patients, which suggests there is room to make these decisions better. The investigators developed a computer program called Revaz AI. It uses artificial intelligence (AI) that has learned from the health records of more than 38,000 past patients with coronary artery disease in Alberta. When given a new patient's health information, Revaz AI estimates that person's risk of dying or having a major heart problem, such as a heart attack, stroke, heart failure, or the need for another procedure, over the next 90 days to 5 years, under each of the three treatment options. In testing on past patient records, Revaz AI's predictions were more accurate than the risk scores doctors currently use. A separate study estimated that using it could improve treatment choices and reduce health care costs. However, Revaz AI has never been tested in real time with real patients. The central question of this trial is: Do patients do better over 5 years when the heart team can see Revaz AI's risk estimates during its discussion, compared with the usual way of deciding? The investigators will also look at whether the tool changes treatment decisions, whether it makes the team more confident in its recommendations, whether patients feel better in daily life, and whether it saves the health care system money. The study will take place at two Canadian hospitals: Foothills Medical Centre in Calgary and the University of Ottawa Heart Institute. Together, their heart teams discuss about 900 patients each year. The investigators plan to enroll 712 adult patients whose cases have been referred to the heart team. Each patient who agrees to join will be assigned by chance, like a coin flip, to one of two groups. In one group, Revaz AI's risk estimates for that patient will be shown on screen during the heart team's virtual meeting, alongside all the usual information. In the other group, the heart team will discuss the case in the usual way, without Revaz AI. Assigning patients by chance ensures the two groups are alike, so any difference in results can be traced to Revaz AI. Importantly, Revaz AI does not make decisions: in both groups, the heart team makes the recommendation, and each patient and their doctor make the final treatment choice together, just as they do now. The investigators will then follow every patient for 5 years. Most of the follow-up information - hospital stays, procedures, and major heart problems - will come from existing health databases, so patients do not need extra hospital visits. The investigators will also contact patients four times (at about 3 months, 1 year, 3 years, and 5 years) with short questionnaires about their symptoms and quality of life. The main measure is the proportion of patients who have a major heart problem or die within 5 years of treatment. Based on past data, about 40% of similar patients experience one of these events within 5 years. The study is designed to detect whether Revaz AI can reduce this to 30%. Independent statisticians will analyze the results, and an independent safety board of experts not involved in the study will review the data regularly and can stop the study if any safety concern appears. The study is led by university researchers with heart specialists at both hospitals. The lead researcher who co-founded the company that makes Revaz AI will stay at arm's length from the study's conduct and analysis, which will be handled by independent team members. All patient information will be coded and stored on secure hospital and university servers. No AI tool for choosing coronary artery disease treatment has ever been tested in a rigorous trial like this. If Revaz AI improves outcomes, patients with complex heart disease could receive treatment decisions tailored to them, and the tool could be adopted by hospitals across Canada and beyond. If it does not, the study will still teach the medical community valuable lessons about how doctors and AI tools work together - knowledge that will shape the safe use of AI in health care.

The goal of this clinical trial is to investigate the use of Lemborexant as a treatment for moderate to severe Cannabis Use Disorder (CUD). The main questions it aims to answer are: 1. Is Lemborexant safe, feasible, and tolerable to use in the CUD population? 2. Will the use of Lemborexant for CUD help to decrease cannabis use, improve sleep, decrease cannabis withdrawal symptoms, and improve cognition? Researchers will compare 10mg Lemborexant to placebo. Participants will: * Take 10mg Lemborexant (or placebo) nightly for 21 nights (treatment phase). * Wear an actigraphy watch continuously for the treatment phase. * Complete a pre-screen survey, attend an in-person screening session, 4 in-person lab visits (weekly from days 0-21), and a virtual follow-up visit 2 weeks after the treatment phase. * Complete a short daily survey for 35 days total.

Resuscitation from a cardiac arrest is a common reason for admission to an intensive care unit (ICU). Because the brain is highly vulnerable to oxygen deprivation, severe brain damage often occurs during a cardiac arrest. Even when the heart has been restarted, there may continue to be reduced blood flow and oxygen delivery to the brain for many hours. ICU professionals generally do not use any tools to detect low oxygen delivery to the brain. Most patients admitted to the ICU are initially in a coma and many will never awaken. Even if they regain consciousness, there may be long-term cognitive and functional disabilities. There are currently no specific treatments available to ICU professionals that are proven to limit brain damage and improve outcomes. Cerebral oximetry is a non-invasive, painless, safe, and easy-to-use tool that detects reduced oxygen delivery to the brain using a sensor over the forehead. Previous research shows that reduced brain oxygen levels \[(regional oxygen saturation (RSO2)\] are predictive of a lower chance of awakening and having a good neurological recovery. This study will assess treatment guided by cerebral oximetry during the initial 48 hours following cardiac arrest. Patients that are in a coma after their circulation has been restarted will be randomly allocated to either usual care based on international guidelines or a protocol aimed at maintaining RSO2 above 60% on both sides of the brain. Cerebral oximetry will be recorded in all patients, but doctors will only be aware of it in one group. If RSO2 drops below 60% for more than 5 minutes, doctors will try to increase it. Actions taken to increase RSO2 may include raising the blood pressure by giving more intravenous fluid or using life-support drugs ("vasoconstrictors" like norepinephrine), stimulating the heart to pump more strongly with medications ("inotropes" like dobutamine, milrinone, or epinephrine), adjusting ventilator settings (to increase the amount of oxygen dissolved in blood or raise carbon dioxide levels, which increases blood flow to the brain), lowering the head of the bed (to increase blood flow to the brain), or giving a blood transfusion (only if the patient has anemia). When RSO2 has been corrected to at least 60% for more than 2 hours, doctors may reverse previous interventions. If they are unable to achieve the goal of 60%, they may lower the target. Efforts to maintain RSO2 in the target range will continue for 48 hours. Investigators will assess how well the protocol works and whether it helps avoid critically low brain oxygen levels. Investigators will also measure various "biomarkers" in the blood that are released when the brain is damaged to see if they are lower when cerebral oximetry is used to guide treatment.

The goal of this clinical trial is to examine the effect of Cannabis components, THC and CBD, on cognition and bladder symptoms in people with Multiple Sclerosis (MS). Participants will complete questionnaires and cognitive tests. They will be randomly assigned to receive either CBD or THC oil and will take the study drug for 15 weeks.

Foreign body airway obstruction (FBAO, choking) is a life-threatening emergency requiring time-sensitive treatment to prevent severe injury or deaths. Traditional treatments taught in first aid courses include abdominal thrusts, back blows, and chest compressions or thrusts. Currently, first aid guidelines recommend different treatments for adults, child and infants. Until recently, data on these techniques was limited to case series from the late 1900's. To further improve our knowledge of which treatment is most effective and safest for patients, this study will collect data on choking incidents in Alberta, Canada. This study will focus on infants aged 2 years or younger.

The primary goals of this phase 2 clinical trial are to determine the feasibility, safety, and tolerability of oral Fecal Microbiota Transplantation (FMT) in adolescents (aged 13-17) with Attention-Deficit/Hyperactivity Disorder (ADHD).

Foreign body airway obstruction (FBAO, choking) is a life-threatening emergency requiring time-sensitive treatment to prevent severe injury or deaths. Traditional treatments taught in first aid courses include abdominal thrusts, back blows, and chest compressions or thrusts. Currently, first aid guidelines recommend different treatments for adults, child and infants. Until recently, data on these techniques was limited to case series from the late 1900's. To further improve our knowledge of which treatment is most effective and safest for patients, this study will collect data on choking incidents in Alberta, Canada. This study will focus on adults and children over the age of 2 years.

Patients requiring life support therapies in intensive care units are at very high risk of hospital-acquired infections. An important source of these infections is the accumulation of pathogenic bacteria in the microbiome of their gut. We hypothesize that treatment with an enteral synbiotic (combination of probiotic and prebiotic), which has been specifically designed to combat pathogen colonization in the gastrointestinal tract, will be safe and effective to reduce pathogen levels in the gut, and potentially reduce infections. We are conducting a phase 1b randomized, open-label, controlled trial to assess safety biological efficacy of enteral synbiotic therapy to reduce gastrointestinal enteropathogen colonization in adult critically ill patients.

The goal of this randomized controlled trial is to evaluate the efficacy of psilocybin administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce post-traumatic stress disorder (PTSD) symptom burden in adult (aged 18-65) survivors of intimate partner violence (IPV). This trail will test the following 2 aims: AIM 1 : To compare the efficacy of a therapeutic psilocybin dose at improving outcomes on the PCL-5 and CAPS-5 as compared to an active control psilocybin dose in IPV survivors with chronic PTSD. AIM 2: To evaluate the efficacy of psilocybin on quality of life, cognitive function, motor ability, depression, anxiety, and cognitive flexibility. Participants will be asked to: * Complete a 2 part screening process * Attend a baseline assessment * Complete a psychoeducation preparation session(s) * Attend psilocybin administration session (receive high dose \[25mg\] or low dose psilocybin \[1mg\]) * Complete 5-6 weekly sessions of ACT * Repeat outcome measures at 1-week, 4 weeks, 3 months (online questionnaires only), and 6 months post-psilocybin administration.

The goal of this randomized controlled trial is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy as an intervention to reduce symptom burden in adult patients (aged 18-65) with persisting symptoms after concussion (PSaC). This trail will test the following 2 aims: AIM 1 : To test the safety and feasibility of an active psilocybin-assisted psychotherapy to an active control for patients with PSaC. AIM 2: To evaluate the efficacy of an active psilocybin-assisted psychotherapy compared to an active control as a treatment for PSaC. Participants will be asked to: * Complete a 2-part screening process * Attend a baseline assessment * Complete a psychoeducation preparation session(s) * Attend psilocybin administration session (receive high dose \[25mg\] or low dose psilocybin \[1mg\]) * Complete 5 weekly sessions of Acceptance and commitment therapy (ACT) * Repeat outcome measures at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration (online only at 6 months).

The purpose of this study is to determine the importance of the acute subjective experience induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Participants in this study will be given psilocybin in combination with either a placebo or risperidone, an atypical antipsychotic that block the subjective effects of psilocybin.

This trial is a is a prospective, randomized (1:1) placebo-controlled, clinical trial with blinded endpoint assessment of 440 participants with unruptured brain aneurysm planned for endovascular treatment using coiling-only approach (primary coiling or using balloon-assistance but not stenting) to test if oral acetylsalicylic acid (325 mg/ day for a total of 5 days) is superior placebo in preventing clinical and silent strokes. The primary outcome is a clinical or silent stroke at the time of discharge assessed by clinical examination and MRI brain. Participants will return to the clinic or be contacted by phone for the end of study procedures on Day 90 to collect functional outcome data.

This pilot clinical trial will study psilocybin-assisted therapy for adults with advanced cancer who are experiencing demoralization, existential distress, or related psychological concerns. Demoralization can include feelings of hopelessness, helplessness, loss of meaning, and distress related to illness or end of life. The purpose of this study is to assess whether a hybrid group-based psilocybin-assisted therapy program is feasible, acceptable, and safe in adults with advanced cancer. The study will also explore which combination of psilocybin dose and psychotherapy approach may be most promising for a future larger trial. Participants will be randomly assigned by wave to one of four intervention combinations: 25 mg psilocybin with mindfulness-based psilocybin-assisted therapy, 25 mg psilocybin with standard psilocybin-assisted therapy, 5 mg psilocybin with mindfulness-based psilocybin-assisted therapy, or 5 mg psilocybin with standard psilocybin-assisted therapy. The psilocybin dose will be blinded, meaning participants and some members of the study team will not know which dose was assigned. Psychotherapy approach will not be blinded. The study will enroll at least 60 participants across Calgary and Kingston.

1. Background and Rationale: Primary aldosteronism is a hypertension-related disorder where salt restriction/salt loss is a central part of therapy. Dietary salt restriction to sufficient degree is very difficult for most patients and thus medications are frequently required to control blood pressure. Non-pharmacologic means of reducing total body sodium and blood pressure are required and desired by patients. Sauna bathing is a traditional wellness practice associated with extensive sweating and therefore salt loss. We wish to study whether incorporation of sauna bathing into a treatment plan for primary aldosteronism might lower blood pressure without increased medications. A pilot feasibility study is required prior to design of a larger controlled clinical trial. We are looking to conduct a short term simulated sauna study to assess patient acceptability and study feasibility as the primary outcomes. 2. Research Questions and Objectives: This study will test the feasibility of having patients add regular sauna usage to their weekly lifestyle, while being treated for hypertension due to primary aldosteronism. The primary objective will be to assess patient recruitment rates, subject retention, patient acceptability, and patient adherence to regular sauna intervention during a 2-week period, using an a priori "traffic light" decision matrix. The secondary objectives will be to explore change in blood pressure, as measured by a wearable, continuous BP wrist monitor, before and after a 2 week sauna intervention. 3. Methods: The study will occur in the context of routine ongoing care in the Endocrine Hypertension Clinic. Ten patients with primary aldosteronism will be recruited to a 7 week study where we will observe the feasibility and acceptability of wearing a continuous, cuffless, wrist BP monitoring device for 2-week periods prior to, during, and after a 2 week "sauna" therapy program. The sauna therapy will consist of three 30 minute visits to a commercially licensed and insured local sauna club each week for 2 weeks. Standardized subject experience questionnaires will collect feasibility and acceptability data which will be analyzed with a standard red light/yellow light/green light approach to study feasibility conclusions.

The goal of this observational study is to characterize the impact of growth hormone deficiency (GHD) on quality of life, symptom burden, and sleep in adults with traumatic brain injury (TBI), and to evaluate whether these outcomes improve with growth hormone replacement therapy. The main questions it aims to answer are: * Does quality of life, as measured by the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA), differ between adults with TBI and GHD compared to those with TBI and no GHD? * Do fatigue, cognition, mood, post-concussion symptoms, body image, libido, perceived stress, and sleep architecture differ between these two groups? * Among participants with GHD who begin growth hormone replacement therapy, do symptom burden and quality of life improve over a 12-week treatment period? Eligible participants will be asked to complete baseline questionnaires and undergo testing for growth hormone deficiency (glucagon stimulation testing). A subset of participants will also complete objective sleep assessments using actigraphy and at-home polysomnography. For those who are diagnosed with growth hormone deficiency and choose to pursue treatment, questionnaires will be repeated bi-weekly while receiving growth hormone replacement therap

This is a randomized controlled trial to determine if lower intraabdominal operating pressure reduces post-operative pain in patients scheduled to undergo laparoscopic uterosacral suspension surgery of the uterus or vaginal vault.

The primary objectives of this present study are to examine whether a continuous interscalene block of a total duration of 48 hours reduces the incidence of rebound pain comparatively to single-shot interscalene block, through the evaluation of the NRS scores at rest and on movement in the postoperative period at 24, 48, 72 and 96 hours as well as the total opioid consumption in the same timeframe for patients undergoing total shoulder arthroplasty. Rebound pain has been defined in some studies as the "the transition from well-controlled pain (numerical rating scale \[NRS\] ≤3) while the block is working to severe pain (NRS ≥7) within 24 h of block performance."

Background \& Rationale: One in ten Canadian youth have migraine, a disabling neurological disease that is more common in females and characterized by moderate-severe disabling headaches. Migraine attacks occur in a cycle that begins with a prodromal phase, followed by aura, a pain phase (headache), and finally a postdrome phase when the pain is resolved but other symptoms persist. The prodrome is recognized by \~90% of all youth with migraine, occurs up to 24 hours before headache onset, and consists of a variety of symptoms including, but not limited to, food cravings, fatigue, yawning, mood changes, and sensory hypersensitivity (e.g., light sensitivity). Prodromal symptoms are disabling and frequently graded as moderate to severe. All acute migraine treatments for youth have been studied for use in the pain phase, with the greatest treatment success early in this phase. Unfortunately, only \~1/3 of youth achieve pain freedom within two hours. Recently, a groundbreaking trial found that treatment during the prodrome could prevent the pain phase, although prodromal treatment does not exist for youth. In considering the most innovative, safe, and patient-centered prodromal intervention, remote electrical neuromodulation (REN) is the obvious choice. The investigator's engagement with 175 youth with migraine and their caregivers shows that REN is preferred when pill-based interventions are ineffective or impractical. REN has none of the limitations of pill-based prodromal treatment. The REN device is wearable, battery-operated, worn on the upper arm, and controlled wirelessly by a smartphone application. REN electrically stimulates sensory nerves in the arm below their perceived pain thresholds, but above their depolarization thresholds, to induce a conditioned pain modulation response in the brain to modulate incoming migraine pain signals. Clinical trial and observational studies in youth with migraine have shown REN's safety and efficacy for home-based treatment during the pain phase and led the FDA to clear its use in youth \>8 years. In the adolescent trial, 71% of participants had pain relief at two hours, there were no serious adverse events (AE), and only one device-related AE (transient arm pain) occurred. Also, emerging data show that adults with migraine in the prodrome phase display pain facilitation due to a deficit in pain modulation. Thus, REN's mechanism of action is likely to be more effective during the prodrome vs. the pain phase as it can "turn on" deficient pain modulatory areas earlier when they are most impaired. Research Question \& Objectives: The investigators aim to determine the feasibility of implementing REN treatment during the prodrome to prevent migraine pain in youth with migraine, and hypothesize that: 1. trial design will be feasible 2. REN will be feasible for prodromal treatment, with \>80% of participants using their assigned device to treat a qualifying prodrome. The following feasibility and acceptability outcomes will be measured: 1. proportion of eligible youth that are enrolled into the screening period, subsequently randomized, and treat a qualifying prodrome with REN. 2. recruitment rate, retention, and withdrawals. 3. participant feedback. All secondary outcomes will be reported descriptively, and adverse events will be recorded and reported. Methods: This study will be a pilot randomized, single centre, double-blind, parallel group, sham-controlled trial comparing active to sham REN for the prevention of headache within 24 hours of treating prodromal symptoms in youth with migraine. Participants will be recruited from headache and neurology clinics at the Alberta Children's Hospital. Eligible and consenting participants will complete an intake visit and enter a 60-day screening period where they will complete electronic daily diaries to determine prodrome or headache occurrence and features. Participants with 3-28 qualifying prodromes during screening, where \>75% are followed by a headache within 6 hours, will be randomized 1:1 to treat one qualifying prodrome with active or sham REN over a 60-day treatment period. Participants will be trained on device use and will be instructed to not use any co-interventions during the qualifying prodrome; if headache onsets after the prodrome, participants will be instructed to use their typical acute treatment. During the treated prodrome, a survey will determine the presence, type, and number of prodromal symptoms. Surveys at 2, 24, and 48 hours post-treatment will record the presence or absence of headache, its characteristics, and AEs. The randomization sequence will be prepared by a biostatistician and will follow randomly ordered blocks of four and six, with variable block sizes. Only research pharmacists will have access to this sequence to prepare consecutively numbered blinded and matched study kits. These kits will contain a restricted mobile phone with only the REN software application pre-installed.

Patch testing remains the gold standard in the diagnosis of allergic contact dermatitis. Patches used in testing consist of a wide spectrum of allergens, with variability in the stability of products over time. Due to limited allergen stability, careful storage and preparation is needed to prevent product degradation over time. Expiration dates are provided by manufacturers to ensure stability and reactivity, while minimizing the risk of product degradation contributing to inaccurate testing results. Preparation of patch series can be time intensive and procurement of allergens comes with an associated economic burden. Expired allergens are not routinely used in patch testing, however many clinics have expired allergens accessible. There is paucity of evidence comparing the reactivity of expired vs non-expired patch series. If expired allergens remain effective, this could result in significant cost-savings and accessibility implications for dermatology practice.

The goal of the PARTUM trial is to determine if taking low-dose aspirin daily for 6 weeks after delivery is similar (non-inferior) to usual care low-molecular-weight heparin injections to prevent venous thromboembolism (VTE: blood clots in the legs or lungs) for postpartum individuals with VTE risk factors.

This is a phase 1 clinical trial investigating the use of low-energy Transcranial Ultrasound Stimulation (TUS) to treat Tourette Syndrome (TS). Objectives and Background. TS is a neurodevelopmental condition marked by motor and vocal tics that often resist standard pharmacological or behavioral treatments. Current neuromodulation options like Deep Brain Stimulation (DBS) are invasive, while non-invasive methods like TMS lack the precision to reach deep brain structures. The study aims to: 1. Evaluate tolerability: Assess TUS safety in older adolescents and adults with TS. 2. Test efficacy: Compare TUS at the intralaminar thalamic nuclei (CM/Pf/Voi) and the supplementary motor area (SMA) against a sham treatment to see if it reduces tic frequency and severity. 3. Optimize protocols: Determine if dual-target or multiple-session stimulation is more effective than single-target or single-session protocols. TUS uses low energy, pulsed, focused ultrasound to induce transient neuromodulatory responses lasting up to 60 minutes. TUS can precisely target deep structures like the thalamus. Study Methods * Design: A phase 1, double-blind, crossover trial. * Participants: 20 individuals (ages 16+) with a diagnosis of TS and significant tic severity (YGTSS score \> 22 or sub-score \> 15). * Procedure: Participants receive four different modalities over four separate weeks, with 7-day washouts: * TUS of the CM/Pf/Voi only. * TUS of the SMA only. * Combined TUS of both targets. * Sham TUS. * Evaluation: The primary endpoint is the percent change on the Rush Video-Based Tic Rating Scale (RVBTRS). Secondary measures include the Yale Global Tic Severity Scale (YGTSS) and the Premonitory Urges for Tics Scale (PUTS). Because TUS requires extreme precision to hit deep brain targets, every participant undergoes a comprehensive imaging protocol using a 3T GE UHP scanner. * Mapping the Targets: We use Diffusion Tensor Imaging (DTI) and Tractography to locate the specific "wiring" of the individual's brain. This allows to find: * The CM/Pf/Voi (Centromedian-parafascicular complex) in the thalamus. * The SMA (Supplementary Motor Area) in the cortex. * Precision Imaging: High-resolution 1 mm-isotropic T1-weighted, T2-weighted, and Zero Echo Time (ZTE) images are used. ZTE is particularly important as it helps the BabelBrain software account for the thickness and density of the skull, which can deflect ultrasound waves. * Real-Time Tracking: During the actual stimulation, the team uses a Brainsight neuro-navigation system. This acts like a GPS, using the patient's MRI "map" to ensure the ultrasound transducer is perfectly aligned with the target. Innovation This is the first human study to apply TUS to TS patients. By targeting both deep and cortical regions independently or simultaneously, the researchers aim to modulate the "network-level" connectivity implicated in tic generation. Technical Ultrasound Parameters The study uses a custom 128-element phased-array transducer (Sonic Concepts H317) to deliver TUS. * Core Settings: * Frequency: 250 kHz. * Intensity: spatial-peak pulse-average intensity (ISPPA) of 10 W/cm2 * Targeting \& Safety: * BabelBrain Software: Calculates real-time acoustic simulations to correct for bone aberrations and ensure the Mechanical Index (MI) stays below 1.9 and thermal rise remains under 2°C. * Electronic Steering: Allows the focal spot to be moved without physically repositioning the device, enabling coverage of large areas like the SMA or deep structures like the CM/Pf/Voi complex. * Biological Protocols: * Inhibitory: pulse repetition frequency (PRF), 10% duty cycle, lasting 120 seconds. * Excitatory: "theta burst" PRF, 10% duty cycle, lasting 80 seconds. Clinical Assessment Criteria The trial employs three main scales to capture both objective tic data and subjective patient experiences: 1. Rush Video-Based Tic Rating Scale (RVBTRS): * The Primary Measure: This is the only validated tool that provides an objective assessment by analyzing 10-minute video recordings. * Method: Two blinded evaluators count tics and rate their severity across two views: a close-up (head/shoulders) and a full-body frontal view. * Focus: It specifically measures the patient's ability to actively inhibit tics during the recording. 2. Yale Global Tic Severity Scale (YGTSS): * The Gold Standard: A clinician-rated interview that assesses symptoms over the prior 7-10 days. * Scoring: It rates motor and phonic tics separately on five dimensions: number, frequency, intensity, complexity, and interference. * Baseline Requirement: To participate in the trial, patients must have a total tic severity score of at least 22 (or a sub-score of 15). 3. Premonitory Urges for Tics Scale (PUTS): * Self-Report: A 9-item questionnaire where patients rate the intensity of pre-tic sensations (like pressure, itchiness, or tension) on a scale of 1 to 4. * Interpretation: Scores range from 9 to 36; higher scores reflect more distressing urges.

Study Design and Duration: This domain will be conducted as part of ACT-GLOBAL platform trial and will have the nested domain name of REACT. It has a prospective, randomised, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design of up to 1,500 subjects with Acute Ischemic Stroke (AIS) who undergo EVT. Randomisation will be stratified by country/ region, and the IA thrombolytic agent (tenecteplase or alteplase). Minimal sufficient balance algorithm will operate within each stratum to preserve balance on key covariates while maintaining allocation randomness. Participants will be followed for 90 days (or until death, if prior to 90 days). The end of the trial is defined as the date that all participants have completed their Day 90 assessment. Primary outcome data will be determined by simplified, structured method of assessment using the modified Rankin scale (mRS), conducted through centralized telephone interviews or online media performed by central trial personnel blinded to treatment assignment and received. Domain Interventions: The intervention group will receive a single dose of local intraarterial thrombolysis using either tenecteplase (at a dose of 0.0625mg/kg; maximum dose of 6.25mg) or alteplase (0.225 mg/kg; maximum dose, 20mg) at the end of EVT procedure plus standard of care while the control group will receive standard of care alone. The selection of the thrombolytic agent will be determined according to local availability. The dose of intraarterial thrombolysis will be increased if the above dose meets prespecified posterior probabilities at the first or second interims. In all eligible patients: 1. Local intra-arterial thrombolysis using either tenecteplase at a dose of 0.0625mg/kg "maximum dose of 6.25mg" or alteplase "0.225 mg/kg; maximum dose, 20mg\* 2. No intra-arterial thrombolysis. * The dose of IA thrombolysis may be doubled to 0.125 mg/kg tenecteplase or 0.45 mg/kg alteplase if this dose shows futility at pre-specified interims Randomization will be stratified by country/ region, the IA thrombolytic agent used (tenecteplase or alteplase). IA thrombolysis will be administered as a one-time treatment.