Racial Differences in Vagal Control of Glucose Homeostasis

NCT02365285 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 141552
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites.

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

• Change in Oxidative Stress: Baseline to 2 Hours

  Measure F-2 isoprostanes as a marker of oxidation

  Baseline to 2 hours

• Change in Oxidative Stress: Baseline to 4 Hours

  Measure F-2 isoprostanes as a marker of oxidation

  Baseline to 4 hours

Study Arms (2)

Galantamine 16 mg then placebo

EXPERIMENTAL

Galantamine 16 mg po one time dose then placebo on 2nd visit

Drug: Galantamine; Drug: Placebo Oral Capsule; Drug: Intralipid; Drug: Heparin

Placebo then Galantamine 16 mg

PLACEBO COMPARATOR

Placebo capsule po one time dose then Galantamine 16 mg on 2nd visit

Drug: Galantamine; Drug: Placebo Oral Capsule; Drug: Intralipid; Drug: Heparin

Interventions

Galantamine DRUG

16 mg po prior to the infusion of intralipid

Also known as: Razadyne

Galantamine 16 mg then placebo; Placebo then Galantamine 16 mg

Placebo Oral Capsule DRUG

Placebo oral capsule prior to the infusion of intralipid/heparin

Galantamine 16 mg then placebo; Placebo then Galantamine 16 mg

Intralipid DRUG

Intralipid 20% will be infused at 0.8 mL/m2/min for 4h after oral placebo or Galantamine

Also known as: I.V. Fat Emulsion

Galantamine 16 mg then placebo; Placebo then Galantamine 16 mg

Heparin DRUG

heparin bolus of 1000 U will be followed by 200 U/h infusion for 4h after oral placebo or Galantamine

Galantamine 16 mg then placebo; Placebo then Galantamine 16 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female
• African American or white (race will be self-defined, but only subjects who report both parents of the same race will be included)
• years old
• BMI 30-45 Kg/m2
• Not pregnant or breastfeeding

You may not qualify if:

• 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 atrioventricular (AV) block)
• Significant weight change \>5% in the past 3 months
• Impaired hepatic function (AST and/or Alanine transaminase (ALT) \> one and one half times (1.5X) upper limit of normal range)
• Impaired renal function (eGFR \<60ml/min)
• Users of strong inhibitors of Cytochrome P450 3A4 (CYP3A4) or cytochrome P450, family 2, subfamily D, polypeptide 6 (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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Parsa D, Aden LA, Pitzer A, Ding T, Yu C, Diedrich A, Milne GL, Kirabo A, Shibao CA. Enhanced parasympathetic cholinergic activity with galantamine inhibited lipid-induced oxidative stress in obese African Americans. Mol Med. 2022 Jun 3;28(1):60. doi: 10.1186/s10020-022-00486-5.

  PMID: 35659521 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Galantamine; soybean oil, phospholipid emulsion; Heparin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amaryllidaceae Alkaloids; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Cyndya Shibao, MD
• Organization: Vanderbilt University Medical Center

cyndya.shibao@vumc.org

615-322-2318

Study Officials

• Cyndya Shibao, MD

  Vanderbilt University Medical Center, Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 28, 2015
• First Posted: February 18, 2015
• Study Start: March 1, 2015
• Primary Completion: October 5, 2017
• Study Completion: October 5, 2017
• Last Updated: March 19, 2019
• Results First Posted: March 19, 2019

Record last verified: 2019-02

Locations

US (1)