ADAM17 and Vascular Function in Diabetes

Study Overview
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Brief Summary
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The objective of this project is to determine the extent to which administration of the dietary supplement phosphatidylserine (PS), a competitive inhibitor of ADAM17 sheddase activity, effects vascular function and insulin-stimulated leg blood flow in subjects with T2D.

Detailed Description
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As part of a randomized (2:1, experimental/placebo), double-blinded parallel design, each of the 34 subjects will complete either 4 weeks of supplementation with 900mg of PS or placebo. Assessment visits (2) will occur pre-intervention and post-intervention and include: 24-hour ambulatory blood pressure measurement (ABPM), Vitals, DEXA scan for body composition, fasting blood work, carotid-femoral pulse wave velocity (cfPWV), brachial and femoral artery FMDs, Femoral blood flow imaging during passive leg movement (PLM), glycocalyx integrity assessment via Glycocheck, and an oral glucose tolerance test (OGTT) with blood flow measurements and beat-to-beat sphygmomanometry via Finometer.

Official Title
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Targeting ADAM17 Activity for Correction of Vascular Insulin Resistance in Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Phosphatidylserine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with a BMI of 25-39 kg/m2, who are 45-64 years of age at randomization. T2D patients classified based on physician diagnosis. No vulnerable populations (e.g., prisoners, pregnant, children) will be enrolled. Exclusion Criteria: Cardiovascular disease including myocardial infraction, heart failure, coronary artery disease, stroke History of chronic renal or hepatic disease Active cancer Autoimmune diseases Immunosuppressant therapy Hormone replacement therapy Excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women) Current tobacco use Pregnancy Bodyweight change ≥5% within the last 6 months

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blinded design with 34 subjects
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Study participants will receive 4 weeks of supplementation with 900mg placebo supplements | Dietary Supplement: Placebo<br>* 4 weeks of placebo supplements<br>|
| Experimental: Phosphatidylserine Supplementation<br>Study participants will receive 4 weeks of supplementation with 900mg phosphatidylserine supplements. | Dietary Supplement: Phosphatidylserine<br>* 4 weeks of 900mg phosphatidylserine supplements<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin-stimulated blood flow | Measure of blood flow during oral glucose tolerance test. Leg blood flow measures will be performed non-invasively via Ultrasound. | baseline and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vascular function | Flow mediated dilation (FMD) in arm and passive limb movement (PLM) in the leg. Blood flow measures will be performed non-invasively via Ultrasound. | Baseline and 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelial dysfunction, vascular function