Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study

Study Overview
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Brief Summary
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Investigators will test the hypothesis that chronic restoration of vagal nerve activity with a central acetylcholinesterase inhibitor improves insulin sensitivity and reduces adipose tissue oxidation in obese African American Women compared to white women.

Detailed Description
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Investigators will test the hypothesis that chronic restoration of parasympathetic nervous system (PNS) activity with a central acetylcholinesterase inhibitor improves insulin sensitivity and reduces adipose tissue oxidation in obese African American women (AAW) compared to white women (WW). A cross-over study will be performed in matched cohorts of AAW and white women subjected to chronic central acetylcholinesterase inhibition with galantamine versus placebo, given orally over a 4-week period. Insulin sensitivity will be measured using the gold standard hyperinsulinemic-euglycemic clamp. Adipose tissue will be obtained through subcutaneous fat biopsies where F2-isoprostanes will be quantified.

Official Title
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Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study

Conditions
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Insulin Sensitivity, Oxidative Stress

Intervention / Treatment
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* Drug: Galantamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Female African American or white (race will be self-defined, but only subjects who report both parents of the same race will be included) 18-60 years old BMI 30-45 Kg/m2 Not pregnant or breastfeeding Exclusion Criteria Pregnant or breastfeeding Diabetes diagnosis (defined by the American Diabetes Association (ADA) criteria)38 Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy. Arrhythmia (first-, second-, and third-degree AV block) Significant weight change >5% in the past 3 months Impaired hepatic function (AST and/or ALT >1.5X upper limit of normal range) Impaired renal function (eGFR <60ml/min) Users of strong inhibitors of CYP3A4 or CYP2D6 Users of other acetylcholinesterase inhibitors such as pyridostigmine or bethanechol History of alcohol or drug abuse Mental conditions rendering the subject unable to understand the nature, scope, and possible consequences of the study Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study Steroid use within 6 weeks prior to study entry Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult Discretion of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galantamine then Placebo, WW<br>4 mg (1 capsule) galantamine twice a day for 4 weeks then placebo (1 capsule) twice a day for 4 weeks in white women (WW) | Drug: Galantamine<br>* Galantamine 4 mg twice a day for 4 weeks<br>* Other names: Razadyne;Drug: Placebo<br>* Placebo 1 capsule twice a day for 4 weeks<br>* Other names: Razadyne;|
| Placebo Comparator: Placebo then Galantamine, WW<br>Placebo (1 capsule) twice a day for 4 weeks then 4 mg (1 capsule) galantamine twice a day for 4 weeks in white women (WW) | Drug: Galantamine<br>* Galantamine 4 mg twice a day for 4 weeks<br>* Other names: Razadyne;Drug: Placebo<br>* Placebo 1 capsule twice a day for 4 weeks<br>* Other names: Razadyne;|
| Experimental: Galantamine then Placebo, AAW<br>4 mg (1 capsule) galantamine twice a day for 4 weeks then placebo (1 capsule) twice a day for 4 weeks in African American Women (AAW) | Drug: Galantamine<br>* Galantamine 4 mg twice a day for 4 weeks<br>* Other names: Razadyne;Drug: Placebo<br>* Placebo 1 capsule twice a day for 4 weeks<br>* Other names: Razadyne;|
| Placebo Comparator: Placebo then Galantamine, AAW<br>Placebo (1 capsule) twice a day for 4 weeks then 4 mg (1 capsule) galantamine twice a day for 4 weeks African American Women (AAW) | Drug: Galantamine<br>* Galantamine 4 mg twice a day for 4 weeks<br>* Other names: Razadyne;Drug: Placebo<br>* Placebo 1 capsule twice a day for 4 weeks<br>* Other names: Razadyne;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin sensitivity | insulin sensitivity will be measured with hyperinsulinemic euglycemic clamps | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin sensitivity, African American, obese