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NCT Number: NCT04321395

Vigabatrin and Insulin Sensitivity

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.

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Key information

Conditions

NAFLD Body Weight Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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
  • persons who are not able to grant voluntary informed consent
  • patients at risk for severe anemia (hemoglobin < 14 g/dL (men) or <12.0 g/dL (women) and/or hematocrit <40% in men or < 37% in women)
  • patients with history of lower limb edema (risk of heart failure)
  • patients with mild or more severe renal insufficiency (CrCl <100 mL/min (men) or <80 mL/min (women))
  • patients with existing peripheral neuropathy
  • women who have active menstrual cycles but are not using birth control (acceptable contraception includes barrier/hormonal/IUD)

Treatment and study plan

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.

Other names: sabril

Primary outcomes

  1. Insulin Sensitivity

    Time frame: 3 weeks after initiation of treatment

    Measured by hyperglycemic euglycemic clamp

Secondary outcomes

  1. Oral Glucose Tolerance

    Time frame: 3 weeks after initiation of treatment

    Measured by 75 gram oral glucose tolerance test

  2. Oral Glucose Insulin Sensitivity

    Time frame: After 3 weeks on drug

    Insulin sensitivity based on oral glucose tolerance. Values are calculated using glucose and insulin from a 3-hour 75 gram oral glucose tolerance test at 0, 2, and 3 hours. Higher values are indicate better insulin sensitivity.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Official study title

The Effect of Vigabatrin on Insulin Sensitivity

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
Mar 25, 2020
Registry last updated
Jan 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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