Evaluating the Efficacy and Safety of Metformin in Vitiligo

Vitiligo Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05607316
• Other study ID #: STUDY00000630
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2023
• Est. completion date: November 1, 2027

Study information

• Verified date: May 2023
• Source: University of Massachusetts, Worcester
• Contact: Nuria Martinez Gutierrez, PhD
• Phone: (774)4554758
• Email: nuria.martinezgutierrez[@]umassmed.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 1, 2027
• Est. primary completion date: July 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Vitiligo

Intervention

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.

Locations

Country	Name	City	State
United States	UMass Chan Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
University of Massachusetts, Worcester

Country where clinical trial is conducted

United States, 

References & Publications (16)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	F-VASI 50	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.	Week 24
Secondary	Safety and tolerability of metformin use in patients with vitiligo.	Proportion of adverse events in patients with vitiligo receiving metformin at week 24.	Week 24
Secondary	Expression of enzyme markers involved in metabolic pathways of interest	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.	Week 24
Secondary	Gene expression and ion abundance following metformin treatment.	Two-fold decrease in gene expression and ion abundance following metformin treatment.	Week 24