Efficacy and Tolerability of Adjunct Metformin for Multibacillary Leprosy

NCT05243654 | Recruiting Phase 2 DMC

• 2 other identifiers: EOCRU.2021.002OXTREC 14-21
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 6

Brief Summary

This trial aims to evaluate the efficacy, tolerability and safety of adjunct metformin added to standard-of-care multi-drug therapy (MDT) in patients with multibacillary leprosy, and explore its effects on immunological endpoints. A double-blind, placebo controlled proof-of-concept trial will be performed in which patients with newly diagnosed multibacillary leprosy will be randomized (1:1) to metformin 1000mg OD versus placebo for 24 weeks in addition to MDT during 48 weeks. The main research question is whether adjunctive metformin, combined with MDT, will improve the clinical outcomes of patients with multibacillary leprosy by mitigating leprosy reactions, thereby reducing nerve damage and corticosteroid use and its associated morbidity. The second aim is to explore whether adjunct metformin, added to MDT, has an acceptable tolerability and safety in patients with multibacillary leprosy.

Conditions

Leprosy; Leprosy, Multibacillary; Neglected Tropical Diseases

Keywords

Leprosy; Multibacillary leprosy; Skin-NTD

Outcome Measures

Primary Outcomes (2)

• The proportion of participants experiencing a leprosy reaction

  Proportion of participants experiencing a leprosy reaction during study follow-up

  48 weeks

• The proportion of participants with at least one adverse events

  The proportion of participants with at least one adverse events within the first 28 weeks of the study

  28 weeks

Secondary Outcomes (15)

• The proportion of participants experiencing a Type 1 Reactions (T1R)

  12, 24 and 48 weeks

• The proportion of participants experiencing a Type 2 Reactions (T2R)

  12, 24 and 48 weeks

• The time to the first leprosy reaction

  48 weeks

• The time to the first Type 1 Reactions (T1R)

  48 weeks

• The time to the first Tipe 2 Reaction (T2R)

  48 weeks

Study Arms (2)

Metformin 1000mg extended release (XR) once daily + standard-of-care MDT

EXPERIMENTAL

Metformin hydrochloride 500mg XR tablets once daily by mouth for 2 weeks, escalating to a target dose of 1000mg XR once daily for another 22 weeks. Each participant will receive the same number of tablets made up of metformin and placebo to maintain the blinding.

Drug: Metformin

Placebo + MDT

PLACEBO COMPARATOR

Matching metformin placebo tablets once daily by mouth for 2 weeks, escalating to two tablets for another 22 weeks. Each participant will receive the same number of tablets made up of metformin and placebo to maintain the blinding.

Drug: Placebo

Interventions

Metformin DRUG

Metformin 1000mg XR OD + standard-of-care MDT

Also known as: Glumin XR

Metformin 1000mg extended release (XR) once daily + standard-of-care MDT

Placebo DRUG

Placebo + standard-of-care MDT

Placebo + MDT

Eligibility Criteria

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

You may qualify if:

• Participant is a male or female, aged ≥18 and ≤65 years.
• Participant is newly diagnosed with MB leprosy and has been receiving MDT ≤ 28 days.
• Participant is willing and able to give informed consent for participation in the trial.
• Participant is willing to adhere to study follow-up schedule for 48 weeks.

You may not qualify if:

• Participant has received MDT \>28 days for the current episode of MB leprosy, prior to study enrolment.
• Presence of leprosy reaction and/or nerve function impairment requiring systemic corticosteroids on screening/enrolment evaluation.
• Participants who have been treated for leprosy in the past.
• Chronic systemic corticosteroid use for any other medical condition on screening evaluation (chronic use defined as ≥ 2 weeks).
• History of diabetes mellitus or diabetes mellitus diagnosed on screening evaluation (random blood glucose is elevated ≥200 mg/dL (or ≥11,1 mmol/L) or fasting blood glucose ≥ 126 mg/dL (or ≥7.0 mmol/L)).
• History of hypoglycaemia (random blood glucose \<55 mg/dL (or \<3.0 mmol/L).
• History of cardiac failure, ischaemic heart disease, alcoholism, history of lactic acidosis or states associated with lactic acidosis such as shock or pulmonary insufficiency, and conditions associated with hypoxia.
• History of intolerance or hypersensitivity to metformin.
• Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m2 calculated by the CKDEPI equation.
• AST or ALT ≥3 times the upper limit of normal (ULN) on screening evaluation.
• Any serious medical condition for which participation in the trial, as judged by the investigator or treating physician, could compromise the well-being of the subject or prevent, limit or confound protocol-specified assessments.
• HIV-positive on screening evaluation.
• Female participant of childbearing age who is pregnant (clinically confirmed or urine dipstick for human chorionic gonadotrophin hormone) or breastfeeding.
• Use of metformin within 12 weeks prior to study enrolment.
• Use of other regular hypoglycaemic agents, including insulin.

Sponsors & Collaborators

• Oxford University Clinical Research Unit Indonesia: lead
• University of Gadjah Mada, Faculty of Medicine: collaborator
• University of Diponegoro: collaborator
• Papua Agency of Health Research and Development (NIHRD): collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Radboud University Medical Center: collaborator
• Oxford University Clinical Research Unit: collaborator

Study Sites (6)

Sitanala Leprosy Hospital

Tangerang, Banten, 15121, Indonesia

RECRUITING

Palangga Health Center

Makassar, South Sulawesi, 92161, Indonesia

RECRUITING

Bajeng Health Center

Makassar, South Sulawesi, 92211, Indonesia

RECRUITING

Abe Pantai Community Health Center

Jayapura, Special Region of Papua, Indonesia

RECRUITING

Hamadi Community Health Center

Jayapura, Special Region of Papua, Indonesia

WITHDRAWN

Jayapura Utara Community Health Center

Jayapura, Special Region of Papua, Indonesia

RECRUITING

Related Publications (1)

• Krismawati H, Muchtar SV, Rahardjani M, Utami NN, Oktaviani M, Puspatriani K, Syamsiah, Imbiri N, Hasvitasari DE, Fajrianti DR, Tarino N, Wulandari F, Kestelyn E, Du DH, van Crevel R, Walker SL, Geskus RB, Geluk A, Hamers RL, Soebono H, Grijsen ML. Metformin as adjunctive therapy in combination with multidrug treatment for multibacillary leprosy: A protocol for a randomized double-blind, controlled Phase 2 trial in Indonesia (MetLep Trial). Wellcome Open Res. 2024 May 9;8:289. doi: 10.12688/wellcomeopenres.19455.2. eCollection 2023.

  PMID: 38808319 DERIVED

MeSH Terms

Conditions

Leprosy; Leprosy, Multibacillary; Neglected Diseases

Interventions

Metformin

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Hardiyanto Soebono, Prof.Dr.dr

  Center of Tropical Medicine, University of Gadjah Mada

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marlous Grijsen, MD, PhD

CONTACT

62-21-23599099; mgrijsen@oucru.org

Mutia Rahardjani, MD, MSc

CONTACT

62-21-23599099; mrahardjani@oucru.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To maintain blinding to treatment allocation, all subjects will receive treatment with identical tablets and the same number of tablets (two tablets once daily).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, randomized double-blind, controlled phase 2 proof-of-concept trial. Subjects will be randomised 1:1 ratio to receive metformin 1000 mg XR tablets OD or matching placebo for 24 weeks. Randomization will be stratified by BI (BI ≥ or \< 4) and participating study site.

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: February 17, 2022
• Study Start: October 1, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ID (6)