NAFLDPhase 2NCT04321395
Vigabatrin and Insulin Sensitivity
A Phase 2 study testing Vigabatrin in people with NAFLD and Obesity, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- What is being tested?
- Vigabatrin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Aug 2021to 15 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University in St. Louis
St Louis, Missouri, 63110
About this study
Official title: The Effect of Vigabatrin on 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.
- Being tested
- Vigabatrin
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VigabatrinDrug
Also called sabril
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.
| Study group | Role | What they receive |
|---|---|---|
| Vigabatrin | Experimental | Not described Receives: Drug: Vigabatrin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
Measured by hyperglycemic euglycemic clamp
Measured: 3 weeks after initiation of treatment
Secondary outcomes (2)
Oral Glucose Tolerance
Measured by 75 gram oral glucose tolerance test
Measured: 3 weeks after initiation of treatment
Oral Glucose Insulin Sensitivity
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.
Measured: After 3 weeks on drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2020
- Study start23 Aug 2021
- Primary completion30 Dec 2023
- Study completion15 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NAFLDStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants will receive vigabatrin
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Klein, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04321395
- Sponsor's protocol ID
- 202006177
- Status last verified
- Dec 2024
- First submitted
- 23 Mar 2020
- Last updated
- 14 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Vigabatrin on Insulin Sensitivity
- ClinicalTrials.gov ID
- NCT04321395
- Acronym / sponsor ID
- 202006177
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 23 Aug 2021 (actual)
- Primary completion
- 30 Dec 2023 (actual)
- Study completion
- 15 May 2024 (actual)
- First posted
- 25 Mar 2020 (actual)
- Results
- Posted 14 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants will receive vigabatrin
| Arm | Type | Receives |
|---|---|---|
| Vigabatrin | Experimental | Drug: Vigabatrin |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VigabatrinAlso: sabrilVigabatrin - 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. | Drug | Vigabatrin |
Primary outcome
Insulin Sensitivity
Time frame: 3 weeks after initiation of treatment
Measured by hyperglycemic euglycemic clamp
2 secondary outcomes
Oral Glucose Tolerance
Time frame: 3 weeks after initiation of treatment
Oral Glucose Insulin Sensitivity
Time frame: After 3 weeks on drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Klein, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vigabatrin in people with NAFLD and Obesity, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin Sensitivity (time frame: 3 weeks after initiation of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.