Abscisic Acid Effects on Glucose Homeostasis and Insulin Sensitivity

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of oral abscisic acid (ABA) on glucose metabolism in subjects with defined prediabetes.

Official Title
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Abscisic Acid Effects on Glucose Homeostasis and Insulin Sensitivity

Conditions
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Pre Diabetes

Intervention / Treatment
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* Other: Hyperinsulemic euglycemic clamp
* Procedure: Muscle Biopsy
* Dietary Supplement: Oral abscisic acid (ABA)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18-65 In good general health as evidenced by medical history or diagnosed with <specify condition/disease> or exhibiting <specify clinical signs or symptoms or physical/oral examination findings> Fasting glucose >5.6 and<7.0 mmol/L and/or HbA1C >5.6 and <6.5 % Ability to take oral medication and be willing to adhere to the <study intervention> regimen Females currently on hormone replacement therapy (HRT) can participate in the study if they have been on HRT for at least 6 months and will continue to be on HRT during the study. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner Agreement to adhere to Lifestyle Considerations throughout study duration. Exclusion Criteria Treated or untreated diabetes 19>BMI<40.0 kg/m2 Blood pressure (BP) ≤ 150mmHg systolic and ≤ 95 mmHg diastolic Current use of medications or antioxidant vitamins or supplements that would impact dependent variables, including glucose metabolism. Past or current ischemic heart disease, stroke, respiratory disease, endocrine or metabolic disease, neurological disease, hematological-oncological disease and free of recent infection (prior 2 weeks) Pregnancy or lactation Treatment with another investigational drug or other intervention within 1 year. Current smoker or tobacco use within the past year. Disqualifying findings on physical examination include cardiac murmurs, diminished pulses or the presence of bruits in the lower extremities, lower extremity thrombophlebitis, evidence of peripheral neuropathy, paresis or edema.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: a randomized, cross-over, placebo-controlled trial will be employed to evaluate the effects of ABA (95ug) twice a day (190ug total per day) for 14 days on tolerability and insulin sensitivity during a hyperinsulinemic euglycemic clamp.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ABA group<br>95 ug 2x/day for 14 days | Other: Hyperinsulemic euglycemic clamp<br>* Following a 12-hour overnight fast at the CRU (including abstinence from caffeine containing foods and beverages), insulin sensitivity will be measured using the criterion method of the euglycemic clamp. Participants will have not performed vigorous physical activity for at least the previous 24 h, and be free of acute illness for the prior 2 weeks. An intravenous catheter will be placed in an antecubital vein for subsequent insulin (40 mU/m2-min) and glucose infusions and for stable isotope (6, 6-2H2) infusions to measure insulin sensitivity.<br>Procedure: Muscle Biopsy<br>* One biopsy taken prior to clamp and a second biopsy taken 30-45 min after the start of the clamp. A biopsy of the Vastus Lateralis muscle will be performed on the leg/thigh using the Bergstrom technique.<br>Dietary Supplement: Oral abscisic acid (ABA)<br>* Those in this group will receive ABA (95 µg ABA and 300 mg of corn starch)<br>|
| Placebo Comparator: Placebo group<br>Corn Starch 300 mg for 14 days | Other: Hyperinsulemic euglycemic clamp<br>* Following a 12-hour overnight fast at the CRU (including abstinence from caffeine containing foods and beverages), insulin sensitivity will be measured using the criterion method of the euglycemic clamp. Participants will have not performed vigorous physical activity for at least the previous 24 h, and be free of acute illness for the prior 2 weeks. An intravenous catheter will be placed in an antecubital vein for subsequent insulin (40 mU/m2-min) and glucose infusions and for stable isotope (6, 6-2H2) infusions to measure insulin sensitivity.<br>Procedure: Muscle Biopsy<br>* One biopsy taken prior to clamp and a second biopsy taken 30-45 min after the start of the clamp. A biopsy of the Vastus Lateralis muscle will be performed on the leg/thigh using the Bergstrom technique.<br>Other: Placebo<br>* Those in this group will receive placebo (300 mg cornstarch)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monitoring adverse events | Adverse events will be monitored at each visit throughout the duration of the study. | 10 weeks | 
| Insulin sensitivity | Insulin sensitivity will be measured using hyperinsulinic euglycemic clamp | 4-6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolism