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Vigabatrin and Insulin Sensitivity

Primary Purpose

NAFLD, Obesity

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Vigabatrin

About this trial

This is an interventional other trial for NAFLD

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Washington University in St. LouisRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vigabatrin

Arm Description

Outcomes

Primary Outcome Measures

Insulin Sensitivity

Measured by hyperglycemic euglycemic clamp

Secondary Outcome Measures

Oral Glucose Tolerance

Measured by 75 gram oral glucose tolerance test

Full Information

NCT ID

NCT04321395

First Posted

March 23, 2020

Last Updated

January 31, 2023

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT04321395

Brief Title

Vigabatrin and Insulin Sensitivity

Official Title

The Effect of Vigabatrin on Insulin Sensitivity

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 23, 2021 (Actual)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NAFLD, Obesity

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Participants will receive vigabatrin

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Vigabatrin

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Vigabatrin

Other Intervention Name(s)

sabril

Intervention Description

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.

Primary Outcome Measure Information:

Title

Insulin Sensitivity

Description

Measured by hyperglycemic euglycemic clamp

Time Frame

3 weeks after initiation of treatment

Secondary Outcome Measure Information:

Title

Oral Glucose Tolerance

Description

Measured by 75 gram oral glucose tolerance test

Time Frame

3 weeks after initiation of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sarah S Farabi, PhD

Phone

3143628554

ssfarabi@wustl.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Samuel Klein, MD

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University in St. Louis

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sarah Farabi

Phone

314-556-4574

ssfarabi@wustl.edu

12. IPD Sharing Statement

Plan to Share IPD

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Vigabatrin and Insulin Sensitivity

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