Evaluating the Efficacy and Safety of Metformin in Vitiligo

September 20, 2024 updated by: John Harris, University of Massachusetts, Worcester

Metformin as a Novel Treatment for Vitiligo by Targeting CD8+ T Cell Metabolism

Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. The investigators hypothesize that oral metformin can regulate the metabolism of CD8+ T cells, reduce their cytotoxic activity and thus serve as a novel treatment for vitiligo.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. It has been reported that the use of metformin correlated with a lower risk of developing vitiligo, suggesting that metformin could potentially mitigate the disease. The investigators found that treating mouse T cells with metformin during activation reduced their mitochondrial respiration and proliferation, while mice treated with metformin reversed their vitiligo. Therefore, the investigators hypothesize that regulation of CD8+ T cell metabolism in vitiligo patients by metformin will reduce their proliferation and cytotoxic activity, resulting in skin repigmentation and thus serve as a novel treatment.

The investigators plan to treat approximately 30 subjects with stable vitiligo.

Metformin is FDA-approved for use with dosing from 500-2000 mg/day. It has a rare risk of lactic acidosis, which can be meaningful in patients with risk factors such as renal insufficiency. This risk is directly proportional to the dose given; therefore, participants will be started at a lower dose (500 mg twice daily) with follow-up to monitor any arising symptoms. Per current clinical recommendations, participants will only be increased to higher-dose metformin (1000 mg twice daily) if the initial dose is tolerated.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Worcester, Massachusetts, United States, 01605
        • UMass Chan Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults 18 years - 100 years of age with stable vitiligo

    • Stable vitiligo is defined as no new spots of depigmentation or expansion of any existing spots for one year;
    • Total body surface area BSA >/= 1%
    • Facial body surface area BSA >/= 0.25%
  • Willingness to participate in the study;
  • Willingness to undergo suction blistering;
  • Non-English speaking adults may be enrolled with the assistance of an interpreter and the use of an IRB-approved short form in the subject's language;
  • Informed consent document signed by the subject;

Exclusion Criteria:

  • Adults unable to consent (adults lacking capacity);
  • Active vitiligo defined by presence of confetti lesions, trichrome lesions, and Koebner's phenomenon;
  • Individuals who are not yet adults (infants, children, teenagers);
  • Pregnant women and/or breastfeeding, or those who have recently delivered a baby within the past 6 months;
  • Prisoners;
  • Systemic immunosuppressive medication (oral corticosteroids) within prior 4 weeks;
  • Topical steroids within the prior 2 weeks;
  • Currently undergoing UVB light therapy or history of light therapy within the past 8 weeks;
  • Unable to return for follow-up visits;
  • Enrolled in a clinical study of any other investigational drug or device;
  • Diabetes, liver disease, or kidney disease;
  • Hypoglycemia as defined by fasting blood glucose <70 mg/dL assessed at a fasting study visit;
  • Prescription medication or cosmetics containing: retinoids, glycolic acid, salicylic acid, or any other remedies that might affect the healing process. Non-medicated moisturizers are allowed. If the person is unsure, they can bring in any products for our review;
  • Self-reported history of chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator;
  • Any other condition or laboratory value that would, in the professional opinion of the investigators, potentially affect the subject's response or the integrity of the data or would pose an unacceptable risk to the subject.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Metformin
Treatment with metformin will be started at 500 mg twice daily and increased to 1000 mg twice daily only after they have tolerated the treatment.
Drug: Metformin Hydrochloride

Consistent with previous studies and clinical recommendations, subjects will initiate treatment at metformin 500 mg twice daily and increase to 1000 mg twice daily only after they have tolerated the treatment (details below).

Study Visit 1 (Week 1) - Study Visit 2 (Week 2) Subjects will be directed to take metformin 500 mg twice daily.

Study Visit 2 (Week 2) - Study Visit 5 (Week 24) If initial metformin dose is tolerated, subjects will be directed to increase the dose to 1000 mg by mouth twice daily for the remainder of the study.

Other Names:
  • Glucophage
  • Glumetza
  • Riomet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Define the different populations of cells by flow cytometry
Time Frame: Week 24
Determine any change in the subpopulations of CD8+ T cells using CD69 and CD103 for Trm and CD122 (IL15Rb chain) as a marker for long-lived Trm; CD44, CD62L, and CD127 for central and effector memory T cells; and CXCR3 to indicate trafficking of CD8+ T cells.
Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Define the inflammatory conditions in the lesions
Time Frame: Week 24
Protein biomarker discovery using Olink® proteomics technology platform (inflammation panel)
Week 24
Measure the abundance of metabolites with untargeted metabolomics in the blister fluid and cells from non-lesional and lesional areas, and in plasma
Time Frame: Week 24
Liquid chromatography-mass spectrometry
Week 24
Vitiligo Area Scoring Index 50% improvement (VASI50) after 6 months of treatment
Time Frame: Week 24
Assess VASI at baseline and after 3 months of starting treatment.
Week 24
Face-Vitiligo Area Scoring Index 50% improvement (F-VASI50) after 6 months of treatment
Time Frame: Week 24
Assess facial VASI at baseline and after 6 months of starting treatment.
Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Massachusetts, Worcester

Investigators

  • Principal Investigator: John E Harris, MD, PhD, Chair, Department of Dermatology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2025

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

October 31, 2022

First Submitted That Met QC Criteria

October 31, 2022

First Posted (Actual)

November 7, 2022

Study Record Updates

Last Update Posted (Actual)

September 24, 2024

Last Update Submitted That Met QC Criteria

September 20, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00000630

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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