search
Back to results

Efficacy and Tolerability of Adjunct Metformin for Multibacillary Leprosy (MetLep)

Primary Purpose

Leprosy, Leprosy, Multibacillary, Neglected Tropical Diseases

Status
Recruiting
Phase
Phase 2
Locations
Indonesia
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
Eijkman Oxford Clinical Research Unit, Indonesia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leprosy focused on measuring Leprosy, Multibacillary leprosy, Skin-NTD

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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 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 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 investigational product within 12 weeks prior to study enrolment.

Sites / Locations

  • Abe Pantai Community Health CenterRecruiting
  • Hamadi Community Health CenterRecruiting
  • Jayapura Utara Community Health CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

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

Placebo + MDT

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

The proportion of participants experiencing a Type 1 Reactions (T1R)
Proportion of participants experiencing a T1R at 12, 24 and 48 weeks.
The proportion of participants experiencing a Type 2 Reactions (T2R)
Proportion of participants experiencing a T2 R at 12, 24 and 48 weeks.
The time to the first leprosy reaction
Time to first leprosy reaction over the full 48 weeks.
The time to the first Type 1 Reactions (T1R)
Time to first T1R over the full 48 weeks.
The time to the first Tipe 2 Reaction (T2R)
Time to first T2R over the full 48 weeks.
The difference in the number of T1R episodes
The difference in the number of T1R episodes
The difference in the number of T2R episodes
The difference in the number of T2R episodes
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.
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.
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.
Total number of adverse events
The total number of adverse events within the first 28 weeks of the trial.
The cumulative corticosteroid usage
Cumulative corticosteroid usage over the full 48 weeks.
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.
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).
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.

Full Information

First Posted
September 30, 2021
Last Updated
February 28, 2023
Sponsor
Eijkman Oxford 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
search

1. Study Identification

Unique Protocol Identification Number
NCT05243654
Brief Title
Efficacy and Tolerability of Adjunct Metformin for Multibacillary Leprosy
Acronym
MetLep
Official Title
Efficacy and Tolerability of Adjunct Metformin in Combination With Multidrug Treatment for Multibacillary Leprosy: A Randomized Double-blind, Controlled Proof-of-Concept Phase 2 Trial in Indonesia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
February 28, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eijkman Oxford 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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leprosy, Leprosy, Multibacillary, Neglected Tropical Diseases
Keywords
Leprosy, Multibacillary leprosy, Skin-NTD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
To maintain blinding to treatment allocation, all subjects will receive treatment with identical tablets and the same number of tablets (two tablets once daily).
Allocation
Randomized
Enrollment
166 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metformin 1000mg extended release (XR) once daily + standard-of-care MDT
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo + MDT
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glumin XR
Intervention Description
Metformin 1000mg XR OD + standard-of-care MDT
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo + standard-of-care MDT
Primary Outcome Measure Information:
Title
The proportion of participants experiencing a leprosy reaction
Description
Proportion of participants experiencing a leprosy reaction during study follow-up
Time Frame
48 weeks
Title
The proportion of participants with at least one adverse events
Description
The proportion of participants with at least one adverse events within the first 28 weeks of the study
Time Frame
28 weeks
Secondary Outcome Measure Information:
Title
The proportion of participants experiencing a Type 1 Reactions (T1R)
Description
Proportion of participants experiencing a T1R at 12, 24 and 48 weeks.
Time Frame
12, 24 and 48 weeks
Title
The proportion of participants experiencing a Type 2 Reactions (T2R)
Description
Proportion of participants experiencing a T2 R at 12, 24 and 48 weeks.
Time Frame
12, 24 and 48 weeks
Title
The time to the first leprosy reaction
Description
Time to first leprosy reaction over the full 48 weeks.
Time Frame
48 weeks
Title
The time to the first Type 1 Reactions (T1R)
Description
Time to first T1R over the full 48 weeks.
Time Frame
48 weeks
Title
The time to the first Tipe 2 Reaction (T2R)
Description
Time to first T2R over the full 48 weeks.
Time Frame
48 weeks
Title
The difference in the number of T1R episodes
Description
The difference in the number of T1R episodes
Time Frame
48 weeks
Title
The difference in the number of T2R episodes
Description
The difference in the number of T2R episodes
Time Frame
48 weeks
Title
The severity of T1R, based on investigator-assessed validated Clinical Severity Scores
Description
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
Title
The severity of T2R, based on investigator-assessed validated Clinical Severity Scores
Description
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
Title
The proportion of participants with at least one serious adverse event
Description
The proportion of participants with at least one serious adverse event within the first 28 weeks of the trial.
Time Frame
28 weeks
Title
Total number of adverse events
Description
The total number of adverse events within the first 28 weeks of the trial.
Time Frame
28 weeks
Title
The cumulative corticosteroid usage
Description
Cumulative corticosteroid usage over the full 48 weeks.
Time Frame
48 weeks
Title
The proportion of participants experiencing clinical nerve function impairment
Description
Proportion of participants experiencing clinical nerve function impairment developed over the full duration of the study.
Time Frame
48 weeks
Title
The difference in Quality of Life between start and end of treatment intervention, and end of study by means of SF-36 questionnaires
Description
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
Title
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.
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 informed consent for participation in the trial. Participant is willing to adhere to study follow-up schedule for 48 weeks. 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 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 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 investigational product within 12 weeks prior to study enrolment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marlous Grijsen, MD, PhD
Phone
62-21-31900971
Email
mgrijsen@eocru.org
First Name & Middle Initial & Last Name or Official Title & Degree
Mutia Rahardjani, MD, MSc
Phone
62-21-31900971
Email
mrahardjani@eocru.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hardiyanto Soebono, Prof.Dr.dr
Organizational Affiliation
Center of Tropical Medicine, University of Gadjah Mada
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abe Pantai Community Health Center
City
Jayapura
State/Province
Papua
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amalia Nurina
Email
anurina@oucru.org
Facility Name
Hamadi Community Health Center
City
Jayapura
State/Province
Papua
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amalia Nurina
Email
anurina@oucru.org
Facility Name
Jayapura Utara Community Health Center
City
Jayapura
State/Province
Papua
Country
Indonesia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amalia Nurina
Email
anurina@oucru.org

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Efficacy and Tolerability of Adjunct Metformin for Multibacillary Leprosy

We'll reach out to this number within 24 hrs