Vigabatrin and Insulin Sensitivity

NCT04321395 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 202006177
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic fatty liver disease (NAFLD) is a common complication of obesity and is associated with an increased risk of developing type 2 diabetes. The hallmark feature of NAFLD is an increase in intrahepatic triglyceride (IHTG) content. Data from studies conducted in rodent models suggest increased IHTG content can alter hepatic vagal afferent nerve (HVAN) activity. In rodent models of obesity and NAFLD, HVAN activity is reduced leading to impaired insulin sensitivity and glucose control. The reduction in HVAN activity is likely due to increased hepatic release of GABA, an inhibitory neurotransmitter, attributable to increased expression of GABA-Transaminase (GABA-T). Pharmacological inhibition of GABA-T in obese mice by treatment with vigabatrin, an irreversible inhibitor of GABA-T improves glucose tolerance and reduces hyperinsulinemia, hyperglycemia, and insulin resistance. It is not known if vigabatrin can also improve metabolic function in people. We propose to conduct a 3-week, single-arm trial to assess the effect size of treatment with vigabatrin on the following specific aims with the larger goal of determining whether a large, randomized controlled trial investigating the effect of vigabatrin is warranted.

Conditions

NAFLD; Obesity

Outcome Measures

Primary Outcomes (1)

• Insulin Sensitivity

  Measured by hyperglycemic euglycemic clamp

  3 weeks after initiation of treatment

Secondary Outcomes (2)

• Oral Glucose Tolerance

  3 weeks after initiation of treatment

• Oral Glucose Insulin Sensitivity

  After 3 weeks on drug

Study Arms (1)

Vigabatrin

EXPERIMENTAL

Drug: Vigabatrin

Interventions

Vigabatrin DRUG

Vigabatrin - Pill, 500 mg twice daily for 7 days (days 0-6), 1000 mg twice daily for 7 days (days 7-13), 1500 mg twice daily for 10 days (days 14-23), 1000 mg twice daily for 7 days (days 24-30), 500 mg twice daily for 7 days (days 31-37) and will discontinue treatment on day 38.

Also known as: sabril

Vigabatrin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• age 25-60 years old
• BMI 30.0-49.9 kg/m2
• IHTG content ≥5.6
• Homeostatic Model of Insulin Resistance (HOMA-IR) Score\>2.5.

You may not qualify if:

• previous bariatric surgery
• structured exercise ≥250 min per week (e.g., brisk walking)
• unstable weight (\>4% change during the last 2 months before entering the study)
• significant organ system dysfunction (e.g., diabetes, severe pulmonary, kidney or cardiovascular disease)
• cancer
• polycystic ovary syndrome
• major psychiatric illness (including suicidal ideation or previous suicide attempts)
• conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders)
• regular use of tobacco products
• excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women)
• use of medications that are known to affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued for this study
• pre-existing visual field deficits; or those at high risk of irreversible vision loss, including patients with retinopathy or glaucoma
• pregnant or lactating women
• conditions that render subject unable to complete all testing procedures (e.g. aversion to needles, metal implants that prevent magnetic resonance imaging
• persons who are unable or unwilling to follow the study protocol

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Interventions

Vigabatrin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Assistant Professor
• Organization: Washington University in St. Louis

ssfarabi@wustl.edu

314-362-8708

Study Officials

• Samuel Klein, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive vigabatrin

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 25, 2020
• Study Start: August 23, 2021
• Primary Completion: December 30, 2023
• Study Completion: May 15, 2024
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)