Insulin Sensitivity, Oxidative Stress
Conditions
Keywords
insulin sensitivity, African American, obese
Brief summary
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
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.
Interventions
DRUGGalantamine
Galantamine 4 mg twice a day for 4 weeks
DRUGPlacebo
Placebo 1 capsule twice a day for 4 weeks
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| insulin sensitivity | 4 weeks | insulin sensitivity will be measured with hyperinsulinemic euglycemic clamps |
Countries
United States
Outcome results
None listed