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RecruitingNCT05243654MetLepUpdated Aug 7, 2025

Efficacy and Tolerability of Adjunct Metformin for Multibacillary Leprosy

A Phase 2 interventional study of Metformin and Placebo in Leprosy, Leprosy, Multibacillary and Neglected Tropical Diseases, sponsored by Oxford University Clinical Research Unit Indonesia. Recruiting at 6 sites in Indonesia. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-08-07.

Sponsored by Oxford University Clinical Research Unit Indonesia · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Oct 2022; still recruiting 4 years 1 month later.
Phase
Phase 2
Study type
Interventional
Enrollment
166
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the detailed description

A double-blind, placebo-controlled randomized proof-of-concept Phase 2 trial will be performed evaluating the efficacy, safety and tolerability of adjunct metformin combined with standard of care MDT to mitigate leprosy reactions. 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 trial aims to enroll 166 patients, aged between 18-65 years old, in leprosy endemic areas in Indonesia. Primary endpoints are the proportion of participants experiencing a leprosy reaction during the full duration of the study and the proportion of participants with at least one adverse event within the first 28 weeks of the study. Secondary endpoints are the severity and time to first leprosy reaction, the number of leprosy reactions, the cumulative corticosteroid usage, and quality of life. The total study follow-up is 48 weeks.

This METLEP trial is financially supported by the Leprosy Research Initiative (grant number: FP20\4).

02

Conditions studied

  • Leprosy
  • Leprosy, Multibacillary
  • Neglected Tropical Diseases

Keywords

  • Leprosy
  • Multibacillary leprosy
  • Skin-NTD
03

In context

Leprosy

52 studies on the registry are indexed under Leprosy; 13 are open to participants now.

This study's planned enrollment of 166 is above the median of 70 across 41 interventional studies indexed under Leprosy.

Browse Leprosy studies →

Lead sponsor

Oxford University Clinical Research Unit Indonesia is the lead sponsor of 4 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 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 for participation in the trial.
  • Participant is willing to adhere to study follow-up schedule for 48 weeks.

Exclusion criteria

Exclusion Criteria:

  • 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 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 to metformin.
  • Estimated (eGFR) ≤30 mL/min/1.73m2 calculated by the CKDEPI equation.
  • or ALT ≥3 times the (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.
  • -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.
  • Participation in another research trial involving an product within 12 weeks prior to study enrolment.
Terms in these criteria, in plain language(8)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
166 participants (estimated)

Study arms

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

    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 comparator
    Placebo + MDT

    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 1000mg XR OD + standard-of-care MDT

    Also known as: Glumin XR

  • DrugPlacebo

    Placebo + standard-of-care MDT

06

What researchers measure

Primary outcomes

  1. The proportion of participants experiencing a leprosy reaction

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

    Time frame: 48 weeks

  2. 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

    Time frame: 28 weeks

Secondary outcomes

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

    Proportion of participants experiencing a T1R at 12, 24 and 48 weeks.

    Time frame: 12, 24 and 48 weeks

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

    Proportion of participants experiencing a T2 R at 12, 24 and 48 weeks.

    Time frame: 12, 24 and 48 weeks

  3. The time to the first leprosy reaction

    Time to first leprosy reaction over the full 48 weeks.

    Time frame: 48 weeks

  4. The time to the first Type 1 Reactions (T1R)

    Time to first T1R over the full 48 weeks.

    Time frame: 48 weeks

  5. The time to the first Tipe 2 Reaction (T2R)

    Time to first T2R over the full 48 weeks.

    Time frame: 48 weeks

  6. The difference in the number of T1R episodes

    The difference in the number of T1R episodes

    Time frame: 48 weeks

  7. The difference in the number of T2R episodes

    The difference in the number of T2R episodes

    Time frame: 48 weeks

  8. The severity of T1R, based on investigator-assessed validated Clinical Severity Scores

    The severity of T1R based on the Modified Type 1 Reactions Clinical Severity Scale. The score ranges from 0-48. A higher score means a worse outcome.

    Time frame: 48 weeks

  9. The severity of T2R, based on investigator-assessed validated Clinical Severity Scores

    The severity of T2R based on the ENLIST ENL Severity Scale. The score ranges from 0-30. A higher score means a worse outcome.

    Time frame: 48 weeks

  10. The proportion of participants with at least one serious adverse event

    The proportion of participants with at least one serious adverse event within the first 28 weeks of the trial.

    Time frame: 28 weeks

  11. Total number of adverse events

    The total number of adverse events within the first 28 weeks of the trial.

    Time frame: 28 weeks

  12. The cumulative corticosteroid usage

    Cumulative corticosteroid usage over the full 48 weeks.

    Time frame: 48 weeks

  13. The proportion of participants experiencing clinical nerve function impairment

    Proportion of participants experiencing clinical nerve function impairment developed over the full duration of the study.

    Time frame: 48 weeks

  14. The difference in Quality of Life between start and end of treatment intervention, and end of study by means of SF-36 questionnaires

    The difference in Quality of Life between start and end of treatment intervention, and end of study by means of the 36-Item short form survey instrument (SF-36). This is a 36-item patient-reported questionnaire that covers eight health domains. Scores for each domain are 0 to 100, with a higher score defining a more favorable health state (0 points means maximum impact on quality of life, 100 means no impact on quality of life).

    Time frame: 24 and 48 weeks

  15. The difference in Quality of Life between start and end of treatment intervention, and end of study by means of the Dermatology Life Quality Index (DLQI) questionnaires.

    The difference in Quality of Life between start and end of treatment intervention, and end of study by means of the Dermatology Life Quality Index (DLQI). The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0 points. A higher score defines a less favorable health state and the more quality of life is impaired.

    Time frame: 24 and 48 weeks

07

Study locations

5 of 6 sites recruiting
  • Sitanala Leprosy Hospital
    Tangerang, Banten 15121, Indonesia
    Recruiting
  • Palangga Health Center
    Makassar, South Sulawesi 92161, Indonesia
    Recruiting
    • Nandya A Mulyadi, MD · Contactnmulyadi@oucru.org · +622123599099
    • Sri Vitayani, MD, PhD · Contactsrivita711@gmail.com · +6281341821336
    • Sri Vitayani, MD,PhD · Principal investigator
  • Bajeng Health Center
    Makassar, South Sulawesi 92211, Indonesia
    Recruiting
    • Nandya A Mulyadi, MD · Contactnmulyadi@oucru.org · +622123599099
    • Sri Vitayani, MD, PhD · Contactsrivita711@gmail.com · +6281341821336
    • Sri Vitayani, MD, PhD · Principal investigator
  • Abe Pantai Community Health Center
    Jayapura, Special Region of Papua, Indonesia
    Recruiting
  • Hamadi Community Health Center
    Jayapura, Special Region of Papua, Indonesia
    Withdrawn

    Not enrolling at this site.

  • Jayapura Utara Community Health Center
    Jayapura, Special Region of Papua, Indonesia
    Recruiting
08

References and documents

Publications

  • 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. PubMed 38808319 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 7, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05243654
Lead sponsor
Oxford University Clinical Research Unit Indonesia
Collaborators
University of Gadjah Mada, Faculty of Medicine, University of Diponegoro, Papua Agency of Health Research and Development (NIHRD), London School of Hygiene and Tropical Medicine, Radboud University Medical Center, Oxford University Clinical Research Unit
Responsible party
Sponsor
First posted
Feb 17, 2022
Start date
Oct 1, 2022
Primary completion
Aug 31, 2026 (estimated)
Completion
Sep 30, 2026 (estimated)
Last update
Aug 7, 2025

Study contacts

Marlous Grijsen, MD, PhD
Contact
mgrijsen@oucru.org
62-21-23599099
Mutia Rahardjani, MD, MSc
Contact
mrahardjani@oucru.org
62-21-23599099
Hardiyanto Soebono, Prof.Dr.dr
principal investigator · Center of Tropical Medicine, University of Gadjah Mada

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Metformin

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