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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 166
- 试验地点
- 6
- 主要终点
- The proportion of participants experiencing a leprosy reaction
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
To maintain blinding to treatment allocation, all subjects will receive treatment with identical tablets and the same number of tablets (two tablets once daily).
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •Participation in another research trial involving an investigational product within 12 weeks prior to study enrolment.
研究组 & 干预措施
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.
干预措施: Metformin (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
The proportion of participants experiencing a leprosy reaction
时间窗: 48 weeks
Proportion of participants experiencing a leprosy reaction during study follow-up
The proportion of participants with at least one adverse events
时间窗: 28 weeks
The proportion of participants with at least one adverse events within the first 28 weeks of the study
次要结局
- The difference in the number of T1R episodes(48 weeks)
- The difference in the number of T2R episodes(48 weeks)
- The severity of T1R, based on investigator-assessed validated Clinical Severity Scores(48 weeks)
- The severity of T2R, based on investigator-assessed validated Clinical Severity Scores(48 weeks)
- The proportion of participants with at least one serious adverse event(28 weeks)
- Total number of adverse events(28 weeks)
- The time to the first leprosy reaction(48 weeks)
- The time to the first Type 1 Reactions (T1R)(48 weeks)
- 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 Tipe 2 Reaction (T2R)(48 weeks)
- The cumulative corticosteroid usage(48 weeks)
- The proportion of participants experiencing clinical nerve function impairment(48 weeks)
- The difference in Quality of Life between start and end of treatment intervention, and end of study by means of SF-36 questionnaires(24 and 48 weeks)
- 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.(24 and 48 weeks)