Evaluating the Efficacy and Safety of Metformin in Vitiligo

Sponsor

University of Massachusetts, Worcester (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05607316

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Vitiligo	Drug: Metformin Hydrochloride	Phase 2

Detailed Description

Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. Bae et al. 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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open-label (unmasked) studyOpen-label (unmasked) study

Masking:

None (Open Label)

Masking Description:

Open-label (unmasked)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

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 at bedtime for the remainder of the study. Other Names: Glucophage Glumetza Riomet

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 at bedtime for the remainder of the study.

Other Names:

Glucophage

Glumetza

Riomet

Outcome Measures

Primary Outcome Measures

F-VASI 50 [Week 24]
The primary outcome will be 50% of subjects who achieve a facial VASI50 (F-VASI50) after 6 months of treatment. Comparisons will be made from scores at week 24 to baselines scores.

Secondary Outcome Measures

Safety and tolerability of metformin use in patients with vitiligo. [Week 24]
Proportion of adverse events in patients with vitiligo receiving metformin at week 24.
Expression of enzyme markers involved in metabolic pathways of interest [Week 24]
Determination of the effects of metformin treatment on expression of enzyme markers involved in metabolic pathways of interest, as well as definition of the subpopulations of skin cells using protein surface markers at a single cell level., autoreactive CD8+ T cells in the blood of patients with vitiligo treated with metformin.
Gene expression and ion abundance following metformin treatment. [Week 24]
Two-fold decrease in gene expression and ion abundance following metformin treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults 18 years and older with stable vitiligo
Stable vitiligo is defined as no new spots of depigmentation or expansion of any existing spots for one year;
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.