Clinical trial NCT03014323: Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study
Official title: Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Insulin Sensitivity
Oxidative Stress
Keywords: insulin sensitivity
African American
obese
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2017-01-09
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: insulin sensitivity
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Cyndya Shibao
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center, Clinical Pharmacology
name: Cyndya A Shibao, MD
role: PRINCIPAL_INVESTIGATOR
References: