Ketogenic Diet

Rationale: Pasireotide is a second line medical treatment for acromegaly that can add value for patients with insufficient control of disease on 1st generation SRL, or 1st generation SRL + pegvisomant. A well-known advserse effect of pasireotide is development of hyperglycemia in 50-70% of cases. Eucaloric very-low carbohydrate ketogenic diet (VLCKD) improves hemoglobin a1c (HbA1c) and fasting plasma glucose (FPG) levels and can show even a long-term effect on glucose regulation in patients with acromegaly. Moreover, the eucaloric VLCKD has improved disease control in patients with acromegaly. Objective: The primary objective of this study is to evaluate the change in HbA1c from start of intervention (baseline of the core study) to post-four months of ketogenic diet compared to standard of care (core study) in patients developing pasireotide-induced hyperglycemia.The secondary objectives are to evaluate: * Differences between eucaloric very-low carbohydrate ketogenic diet and standard of care (diabetes medication) regarding: * Proportion of patients with target HbA1c (\<48mmol/L / \<6.5%) achieved without glucose lowering drugs (beyond metformine monotherapy) in both arms * Evaluation and sustainability of glycaemic control (HbA1c) and (dosage of) anti-diabetic drugs need to reach control * Biochemical control, and symptom score of acromegaly * Quality of life * Proportion of patients on 40 and 60 mg, proportion with normal IGF-1, tolerability, and safety of pasireotide * Exploratory evaluation of all eligible subjects considered for and started with pasireotide treatment to get a better insight into these complicated acromegaly patients and their metabolic profile. * Exploratory evaluation of other timepoints (start of pasireotide) to analyse course of Hba1c development from start of pasireotide until the end of the core study Study design: Study type: multicenter combined observational and interventional randomized controlled study. Allocation: randomized (1:1 ratio). Intervention model: parallel assignment. Masking: non (open-label). Primary purpose: supportive care. Study population: Adult patients with a confirmed diagnosis of acromegaly (for whom surgery is not an option, or for whom surgery has failed) and with inadequately GH and/or IGF-1 control (\>0.8xULN) or active disease symptoms with first-generation SRL, or with inadequately GH and/or IGF-1 control (\>0.8xULN) or active disease symptoms on second-line medical treatments for acromegaly (pegvisomant monotherapy or combination therapy with first-generation SRL and pegvisomant or dopamine agonist, respectively) and with a baseline Hba1c \<44 mmol/L (6.2%) - including those pre-treated with metformin in case of HbA1c ≥44 mmol/L (6.2%) and ≤64 mmol/L (8.0%) - in whom pasireotide is considered in the clinical setting. Intervention (if applicable): We aim to include 30 acromegaly patients with pasireotide-induced hyperglycaemia, to ensure that 20 patients complete the 4-month intervention. Subjects will be randomized 1:1 to open-label eucaloric very-low carbohydrate ketogenic diet (\<40 g of carbohydrate) or standard of care (i.e. metformin, followed by sitagliptin (DPP4-inhibitor), incretin-based therapy with liraglutide (GLP-1 receptor agonist), and insulin) at the time hyperglycemia is present. The randomized intervention period is 4 months (core phase of the study). Randomized subjects who reach the end of the randomized phase can continue with the open-label extension, and opt to continue their randomized diet or DM drug treatment or freely choose the other alternative for another 4 months (extension study). Main study parameters/endpoints: Evaluation of effect of treatment with eucaloric very-low carbohydrate ketogenic diet or diabetes medication on glycaemic control of pasireotide: \- Change in HbA1c from start core study to the end of the intervention (ketogenic diet vs standard of care) Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Study participants will have 8 visits to the outpatient clinic over a period of 12-15 months. This comes down to 480 minutes in total. During these visits, physical exam/anthropometric measurements will be performed and 2 blood tubes of 2,5 cc will be collected and 3 QoL questionnaires and one food diary will be filled out (total visit: 60 minutes). The usual burden for a single patient is 3-outpatient visits over a period of 1 year, which takes about 60 minutes in total and with the same volume of blood per visit.

The research study is being conducted to better understand the effects of ketosis on brain functioning and the acute effects of alcohol. Participants will be asked to undergo \~4 weeks of ketogenic diet intervention. The study involves three lab visits: Lab 1 before starting the diet, Lab 2 after about 2 weeks after starting the diet, and Lab 3 after being on the diet for 4 weeks. All of the labs will include an alcohol tolerance test, and blood draws. Lab 1 and Lab 3 will also include an Magnetic resonance imaging scan. Due to scheduling, study procedures at 2 and 4 weeks may occur +/- 3 days. Magnetic resonance imaging (MRI) of the brain will measure levels of nicotinamide adenine dinucleotide (NAD) (a coenzyme that is important for energy metabolism), lactate (a metabolite produced during energy metabolism), and neurotransmitters glutamate and GABA. Alcohol tolerance will be tested using a dose of alcohol (approximately 4-5 alcohol beverages) to will elevate breath alcohol levels to approximately 0.08% to measure the acute effects of alcohol. Blood samples will be collected to measure varying metabolites.

Poniżej znajduje się bardziej płynna i mniej powtarzalna wersja tekstu: This 12-week randomized controlled trial will investigate the effects of dietary patterns with different macronutrient compositions on gut microbiota, intestinal inflammation, gene expression, and metabolic health in healthy adults. Participants will be randomly assigned to one of three dietary interventions: a ketogenic diet (KD), a vegetarian diet (VD), or a control diet (CD) reflecting their habitual mixed dietary pattern. Adherence to the assigned diet will be monitored through dietary records and regular nutritional counseling. The study will evaluate changes in gut microbiota composition, inflammatory biomarkers, transcriptomic profiles, and blood biochemical parameters associated with lipid and glucose metabolism. Blood and stool samples will be collected at predefined time points throughout the intervention, while participants in the KD group will additionally undergo ketone monitoring to assess dietary compliance. By comparing the ketogenic and vegetarian diets with a standard mixed diet, this study aims to determine their effects on gut health, metabolic function, and systemic inflammation, thereby providing evidence to inform dietary recommendations. Ta wersja eliminuje powtórzenia ("diet", "study", "monitor", "effects"), jest bardziej naturalna stylistycznie i odpowiada standardowi językowemu publikacji w czasopismach z zakresu żywienia i medycyny.

Acromegaly is caused by a tumour located at the base of the brain in the pituitary gland that produces too much growth hormone (GH). Symptoms caused by the excess of GH, and consequently increased insulin like growth factor 1 (IGF-1), are disproportionate growth of body parts, fluid retention, snoring and excessive perspiration. The various metabolic changes that occur due to acromegaly increase the risk for insulin resistance, diabetes mellitus, arterial hypertension, sleep apnoea and thus an increased risk of cardiovascular disease if left untreated. The result is signs and symptoms, increased mortality, morbidity, and greatly reduced quality of life (QoL). Normalisation of GH and IGF-1 gives a normalisation of mortality, however morbidity and QoL do not (completely) normalise. After surgery, a somatostatin analogue is the primary medical treatment, however, normalisation occurs in only 40% of patients. Recently, in a proof-of-principle study, the researchers showed that a 2-week ketogenic diet (low in carbohydrates) in patients with somatostatin analogues could significantly reduce IGF-1 values. Patients felt better and sometimes even needed less somatostatin analogues. This proof of concept led to the new hypothesis that acromegaly patients with somatostatin analogues should possibly be treated with a eucaloric low-carbohydrate ketogenic diet for a longer period of time to improve their biochemistry, symptoms and QoL. Additionally, this diet can make a significant contribution in the treatment of insulin resistance and glucose intolerance that often occur in this patient group.

This clinical trial aims to evaluate whether a ketogenic diet (KD), when combined with immunotherapy, can improve immune function and treatment outcomes in patients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), or renal cell carcinoma (RCC). Why Is This Study Important? Immunotherapy is a promising cancer treatment, but not all patients respond well. Research suggests that diet, particularly a high-fat, low-carbohydrate ketogenic diet, may help boost the immune system and make treatments more effective. What Will This Study Examine? Researchers want to understand: Is the ketogenic diet well-tolerated for cancer patients? Does the diet improve immune responses and treatment effectiveness? How Will the Study Work? Participants will be placed into one of two groups: Ketogenic Diet (KD) Group: A structured high-fat, low-carb diet (intermittent schedule: 2 weeks on, 1 week off). Standard Diet (SD) Group: A typical diet with no major changes. Throughout the study, a dietitian will closely support and guide you. Both groups will continue their standard immunotherapy treatment. What Will Participants Do? Write their food intake three times a week to help assess dietary adherence Follow their assigned diet for 10 weeks Have weekly check-ins with a dietitian (in-person at the hospital or via phone) Have weekly blood glucose and ketone level checks using a home device. Provide monthly blood samples to measure immune response during routine immunotherapy infusions Provide stool samples for gut microbiome analysis at the start and end of the study Measure Monthly Weight, body composition, and resting calorie burn Complete quality-of-life questionnaires What Are the Potential Benefits? Improved response to immunotherapy Better understanding of how diet influences cancer treatment Potential for a new supportive strategy for cancer care This study may help uncover ways to enhance cancer treatment through personalized nutrition.