Optimizing Ultrasound-induced Anti-inflammation in Human Subjects
ConditionHealthy Subjects
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age25-50
SponsorUniversity of Virginia
About this trial
This is a feasibility study to determine whether pulsed ultrasound stimulation targeting the splenic nerve or the cervical vagus nerve can elicit an anti-inflammatory immune response in healthy volunteers.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Male or female, aged 25-50 years
Provision of signed and dated informed consent form
Able to comprehend the study goals and procedures, stated willingness to comply with all study procedures, and availability for the duration of the study
Considered English proficient so that the subject can follow verbal commands during the ultrasound procedure
Disqualifiers
Chronic medical conditions, including cancer (in remission or active cancer), cerebrovascular disease, chronic kidney disease, heart conditions (such as heart failure, coronary artery disease, cardiomyopathies), lung disease, liver disease, hypertension, diabetes mellitus type 1 and 2, human immunodeficiency virus infection, primary immunodeficiencies, solid organ or hematopoietic cell transplantation, tuberculosis, and cystic fibrosis, autoimmune disorders (e.g., rheumatoid arthritis, inflammatory bowel disease), sickle cell anemia or other anemia syndromes
Mean systolic and diastolic blood pressure values during screening of ≥160 and ≥100 mm Hg, respectively, hypertension on non-selective beta-blockers and/or alpha-methyl dopa, or hypertension requiring more than two anti-hypertension medications
Obesity (body mass index ≥30 kg/m2)
Use of anti-inflammatory or immunomodulatory medication, such as non- steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or other immunosuppressants, within one week of receiving ultrasound delivery
Trial design
Design model
Parallel
Treatments tested in this trial
Ultrasound stimulation intensity
DeviceA clinical ultrasound transducer will be placed against the abdomen or neck of an individual in order to administer insonification to the splenic nerve.
Ultrasound stimulation site
DeviceA clinical ultrasound transducer will be placed against the abdomen or neck of an individual in order to administer insonification to the splenic nerve and the cervical vagus nerve.
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: Group 1Active comparator 1 intervention
Group B: Group 2Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in concentrations of immune cells and cytokines depending on ultrasound stimulation intensity
The primary outcome is to determine ultrasound intensities that have a biological effect on immune cells measured as a statistically significant change in the level of cytokines produced by immune cells. White blood cells will be isolated from peripheral blood and treated ex vivo with inflammatory stimuli to evaluate their capacity for cytokine production. The cytokines to be measured are (all will be measured in pg/ml): sCD40L; EGF; Eotaxin; FGF-2; FLT-3L; Fractalkine; G-CSF; GM-CSF; GRO; IFNα2; IFNy; IL-1α; IL-1β; IL-1Ra; IL-2; IL-3; IL-4; IL-5; IL-6; IL-7; IL-8; IL-9; IL-10; IL-12p40; IL-12p70; IL-13; IL-15; IL-17A; IL-17E; IL-17F; IL-18; IL-22; IL-27; IP-10; MCP-1; MCP-3; M-CSF; MDC; MIG; MIP-1α; MIP-1β; PDGF-AA; PDGF-AB/BB; TGFα; TNFα; TNFβ; VEGF-A.
Time frame
Immune cells will be stimulated and assessed prior to and within 24 to 48 hours post-ultrasound treatment. Results of Luminex analysis of the pre- and post-ultrasound stimulation supernatants will be compared to quantify the impacts of the treatment.2
Change in concentrations of immune cells and cytokines depending on ultrasound stimulation site
The primary outcome is to determine the effects of spleen-targeted versus cervical vagus-targeted ultrasound stimulation on the inflammatory capacity of immune cells. This will be measured by stimulating white blood cells from peripheral blood ex vivo with inflammatory stimuli to evaluate their capacity for cytokine production. The cytokines to be measured are (all will be measured in pg/ml): sCD40L; EGF; Eotaxin; FGF-2; FLT-3L; Fractalkine; G-CSF; GM-CSF; GRO; IFNα2; IFNy; IL-1α; IL-1β; IL-1Ra; IL-2; IL-3; IL-4; IL-5; IL-6; IL-7; IL-8; IL-9; IL-10; IL-12p40; IL-12p70; IL-13; IL-15; IL-17A; IL-17E; IL-17F; IL-18; IL-22; IL-27; IP-10; MCP-1; MCP-3; M-CSF; MDC; MIG; MIP-1α; MIP-1β; PDGF-AA; PDGF-AB/BB; TGFα; TNFα; TNFβ; VEGF-A.
Time frame
Immune cells will be stimulated and assessed prior to and within 24 to 48 hours post-ultrasound treatment. Results of Luminex analysis of the pre- and post-ultrasound stimulation supernatants will be compared to quantify the impacts of the treatment.Secondary outcomes
1
Distribution of immune cells
The secondary outcome is to determine the effects of ultrasound stimulation on the distribution of immune cells measured as a statistically significant change in the distribution of white blood cells using flow cytometry associated with the inflammatory response following delivery of ultrasound.
Time frame
The secondary outcome will be assessed before and max 48-hours after receiving ultrasound stimulation.Other outcomes
1
Participant comfort, experience, and new-onset sensations by questionnaire
Participants will complete a questionnaire based on a dichotomous scale ("yes" or "no") to evaluate their experience of discomfort and new-onset sensations following ultrasound stimulation.
Time frame
The outcome will be assessed immediately after, within 24 to 48 hours, and 2 weeks after receiving ultrasound stimulationSponsors and contacts
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Source ClinicalTrials.gov