Racial Differences in Vagal Control of Glucose Homeostasis, Chronic Study

NCT ID: NCT03014323

Last Updated: 2018-08-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2018-12-31

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.

Conditions

Insulin Sensitivity; Oxidative Stress

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: EXPERIMENTAL

Galantamine

Intervention Type: DRUG

Galantamine 4 mg twice a day for 4 weeks

Placebo

Intervention Type: DRUG

Placebo 1 capsule twice a day for 4 weeks

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)

Group Type: PLACEBO_COMPARATOR

Galantamine

Intervention Type: DRUG

Galantamine 4 mg twice a day for 4 weeks

Placebo

Intervention Type: DRUG

Placebo 1 capsule twice a day for 4 weeks

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)

Group Type: EXPERIMENTAL

Galantamine

Intervention Type: DRUG

Galantamine 4 mg twice a day for 4 weeks

Placebo

Intervention Type: DRUG

Placebo 1 capsule twice a day for 4 weeks

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)

Group Type: PLACEBO_COMPARATOR

Galantamine

Intervention Type: DRUG

Galantamine 4 mg twice a day for 4 weeks

Placebo

Intervention Type: DRUG

Placebo 1 capsule twice a day for 4 weeks

Interventions

Galantamine

Galantamine 4 mg twice a day for 4 weeks

Intervention Type: DRUG

Placebo

Placebo 1 capsule twice a day for 4 weeks

Intervention Type: DRUG

Other Intervention Names

Razadyne; Razadyne

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Cyndya Shibao

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cyndya A Shibao, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center, Clinical Pharmacology

Locations

Cyndya Shibao

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

141552-specific aim 2

Identifier Type: -

Identifier Source: org_study_id