Evaluating the Efficacy and Safety of Metformin in Vitiligo

NCT05607316 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00000630
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Vitiligo

Keywords

vitiligo; metformin; systemic treatment; stable vitiligo; segmental vitiligo; non-segmental vitiligo

Outcome Measures

Primary Outcomes (1)

• Define the different populations of cells by flow cytometry

  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 Outcomes (4)

• Define the inflammatory conditions in the lesions

  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

  Week 24

• Vitiligo Area Scoring Index 50% improvement (VASI50) after 6 months of treatment

  Week 24

• Face-Vitiligo Area Scoring Index 50% improvement (F-VASI50) after 6 months of treatment

  Week 24

Study Arms (1)

Oral Metformin

EXPERIMENTAL

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

Interventions

Metformin Hydrochloride DRUG

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.

Also known as: Glucophage, Glumetza, Riomet

Oral Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead

Study Sites (1)

UMass Chan Medical School

Worcester, Massachusetts, 01605, United States

Location

Related Publications (16)

• Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su MW, Zhou Y, Deng A, Hunter CA, Luster AD, Harris JE. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014 Feb 12;6(223):223ra23. doi: 10.1126/scitranslmed.3007811.

  PMID: 24523323 BACKGROUND

• Zhang Y, Cai Y, Shi M, Jiang S, Cui S, Wu Y, Gao XH, Chen HD. The Prevalence of Vitiligo: A Meta-Analysis. PLoS One. 2016 Sep 27;11(9):e0163806. doi: 10.1371/journal.pone.0163806. eCollection 2016.

  PMID: 27673680 BACKGROUND

• Salzes C, Abadie S, Seneschal J, Whitton M, Meurant JM, Jouary T, Ballanger F, Boralevi F, Taieb A, Taieb C, Ezzedine K. The Vitiligo Impact Patient Scale (VIPs): Development and Validation of a Vitiligo Burden Assessment Tool. J Invest Dermatol. 2016 Jan;136(1):52-8. doi: 10.1038/JID.2015.398.

  PMID: 26763423 BACKGROUND

• Linthorst Homan MW, Spuls PI, de Korte J, Bos JD, Sprangers MA, van der Veen JP. The burden of vitiligo: patient characteristics associated with quality of life. J Am Acad Dermatol. 2009 Sep;61(3):411-20. doi: 10.1016/j.jaad.2009.03.022. Epub 2009 Jul 3.

  PMID: 19577331 BACKGROUND

• Elbuluk N, Ezzedine K. Quality of Life, Burden of Disease, Co-morbidities, and Systemic Effects in Vitiligo Patients. Dermatol Clin. 2017 Apr;35(2):117-128. doi: 10.1016/j.det.2016.11.002.

  PMID: 28317521 BACKGROUND

• Ogg GS, Rod Dunbar P, Romero P, Chen JL, Cerundolo V. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J Exp Med. 1998 Sep 21;188(6):1203-8. doi: 10.1084/jem.188.6.1203.

  PMID: 9743539 BACKGROUND

• Frisoli ML, Essien K, Harris JE. Vitiligo: Mechanisms of Pathogenesis and Treatment. Annu Rev Immunol. 2020 Apr 26;38:621-648. doi: 10.1146/annurev-immunol-100919-023531. Epub 2020 Feb 4.

  PMID: 32017656 BACKGROUND

• Richmond JM, Bangari DS, Essien KI, Currimbhoy SD, Groom JR, Pandya AG, Youd ME, Luster AD, Harris JE. Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease. J Invest Dermatol. 2017 Feb;137(2):350-358. doi: 10.1016/j.jid.2016.09.016. Epub 2016 Sep 26.

  PMID: 27686391 BACKGROUND

• Sanchez-Rangel E, Inzucchi SE. Metformin: clinical use in type 2 diabetes. Diabetologia. 2017 Sep;60(9):1586-1593. doi: 10.1007/s00125-017-4336-x. Epub 2017 Aug 2.

  PMID: 28770321 BACKGROUND

• Agius L, Ford BE, Chachra SS. The Metformin Mechanism on Gluconeogenesis and AMPK Activation: The Metabolite Perspective. Int J Mol Sci. 2020 May 3;21(9):3240. doi: 10.3390/ijms21093240.

  PMID: 32375255 BACKGROUND

• Cui Y, Chang L, Wang C, Han X, Mu L, Hao Y, Liu C, Zhao J, Zhang T, Zhang H, Zhang Y, Liu Y, Zhao W, Wang J, Liu X, Sun B, Wang G, Kong Q, Han J, Li H. Metformin attenuates autoimmune disease of the neuromotor system in animal models of myasthenia gravis. Int Immunopharmacol. 2019 Oct;75:105822. doi: 10.1016/j.intimp.2019.105822. Epub 2019 Aug 19.

  PMID: 31437793 BACKGROUND

• Tomczynska M, Bijak M, Saluk J. Metformin - The Drug for the Treatment of Autoimmune Diseases; A New Use of a Known Anti-Diabetic Drug. Curr Top Med Chem. 2016;16(19):2223-30. doi: 10.2174/1568026616666160216152324.

  PMID: 26881720 BACKGROUND

• Salvatore T, Pafundi PC, Galiero R, Gjeloshi K, Masini F, Acierno C, Di Martino A, Albanese G, Alfano M, Rinaldi L, Sasso FC. Metformin: A Potential Therapeutic Tool for Rheumatologists. Pharmaceuticals (Basel). 2020 Sep 4;13(9):234. doi: 10.3390/ph13090234.

  PMID: 32899806 BACKGROUND

• Doyle-Delgado K, Chamberlain JJ, Shubrook JH, Skolnik N, Trujillo J. Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline. Ann Intern Med. 2020 Nov 17;173(10):813-821. doi: 10.7326/M20-2470. Epub 2020 Sep 1.

  PMID: 32866414 BACKGROUND

• Cornell S. Comparison of the diabetes guidelines from the ADA/EASD and the AACE/ACE. J Am Pharm Assoc (2003). 2017 Mar-Apr;57(2):261-265. doi: 10.1016/j.japh.2016.11.005. Epub 2017 Jan 5.

  PMID: 28065547 BACKGROUND

• DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014. Epub 2015 Oct 9.

  PMID: 26773926 BACKGROUND

MeSH Terms

Conditions

Vitiligo

Interventions

Metformin

Condition Hierarchy (Ancestors)

Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• John E Harris, MD, PhD

  Chair, Department of Dermatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label (unmasked)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair

Model Details: Open-label (unmasked) study

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 7, 2022
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)