NCT04321395

Vigabatrin and Insulin Sensitivity

Completed Phase 2 Results posted Last updated 14 January 2025

What this trial tests

Phase 2 trial testing Vigabatrin in NAFLD in 4 participants. Completed in 15 May 2024.

Timeline

23 August 2021

Primary endpoint
30 December 2023

15 May 2024

Quick facts

Lead sponsor	Washington University School of Medicine
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	4
Start date	23 August 2021
Primary completion	30 December 2023
Estimated completion	15 May 2024
Sites	1 location across United States

Drugs / interventions tested

• Vigabatrin — full drug profile →

Conditions studied

• NAFLD — all drugs for NAFLD →
• Obesity — all drugs for Obesity →

Sponsor

Washington University School of Medicine

Who can join

Adults 18 to 60, any sex, with NAFLD or Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Insulin Sensitivity Primary · 3 weeks after initiation of treatment

Measured by hyperglycemic euglycemic clamp

Group	Value	95% CI
Vigabatrin	6.82	± 1.7

Oral Glucose Tolerance Secondary · 3 weeks after initiation of treatment

Measured by 75 gram oral glucose tolerance test

Group	Value	95% CI
Vigabatrin	155.5	± 19.2

Oral Glucose Insulin Sensitivity Secondary · 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.

Group	Value	95% CI
Vigabatrin	294	± 56

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Metabolite 2-aminoadipic acid: implications for metabolic disorders and therapeutic opportunities.
   Shi W, Yang Z, Fu P, Yang Y. · · 2025 · cited 4× · PMID 40432896 · DOI 10.3389/fphar.2025.1569020