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

Vanderbilt University Medical Center

Status and phase: Withdrawn; Phase 1

Conditions: Oxidative Stress; Insulin Sensitivity

Treatments: Drug: Galantamine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03014323

141552-specific aim 2

Details and patient eligibility

About

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.

Full 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.

Sex: Female

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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0 participants in 4 patient groups, including a placebo group

Galantamine then Placebo, WW

Experimental group

Description:

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)

Treatment:

Drug: Placebo

Drug: Galantamine

Placebo then Galantamine, WW

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo

Drug: Galantamine

Galantamine then Placebo, AAW

Experimental group

Description:

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)

Treatment:

Drug: Placebo

Drug: Galantamine

Placebo then Galantamine, AAW

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo

Drug: Galantamine