RDVCGH: Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03014323

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Insulin Sensitivity Oxidative Stress	Drug: Galantamine Drug: Placebo	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study

Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Nov 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galantamine then Placebo, WW 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 Galantamine 4 mg twice a day for 4 weeks Other Names: Razadyne Drug: Placebo Placebo 1 capsule twice a day for 4 weeks Other Names: Razadyne
Placebo Comparator: Placebo then Galantamine, WW 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 Galantamine 4 mg twice a day for 4 weeks Other Names: Razadyne Drug: Placebo Placebo 1 capsule twice a day for 4 weeks Other Names: Razadyne
Experimental: Galantamine then Placebo, AAW 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 Galantamine 4 mg twice a day for 4 weeks Other Names: Razadyne Drug: Placebo Placebo 1 capsule twice a day for 4 weeks Other Names: Razadyne
Placebo Comparator: Placebo then Galantamine, AAW 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 Galantamine 4 mg twice a day for 4 weeks Other Names: Razadyne Drug: Placebo Placebo 1 capsule twice a day for 4 weeks Other Names: Razadyne

Outcome Measures

Primary Outcome Measures

insulin sensitivity [4 weeks]
insulin sensitivity will be measured with hyperinsulinemic euglycemic clamps

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts 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