Efficacy and Tolerability of Adjunct Metformin for Multibacillary Leprosy

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат Metformin
  Metformin 1000mg XR OD + standard-of-care MDT
• Препарат Placebo
  Placebo + standard-of-care MDT

Первичные конечные точки

• The proportion of participants experiencing a leprosy reaction [Срок оценки: 48 weeks]
• The proportion of participants with at least one adverse events [Срок оценки: 28 weeks]

Вторичные конечные точки (12)

• The proportion of participants experiencing a Type 1 Reactions (T1R) [Срок оценки: 12, 24 and 48 weeks]
• The proportion of participants experiencing a Type 2 Reactions (T2R) [Срок оценки: 12, 24 and 48 weeks]
• The time to the first leprosy reaction [Срок оценки: 48 weeks]
• The time to the first Type 1 Reactions (T1R) [Срок оценки: 48 weeks]
• The time to the first Tipe 2 Reaction (T2R) [Срок оценки: 48 weeks]
• The difference in the number of T1R episodes [Срок оценки: 48 weeks]
• The difference in the number of T2R episodes [Срок оценки: 48 weeks]
• The severity of T1R, based on investigator-assessed validated Clinical Severity Scores [Срок оценки: 48 weeks]
• The severity of T2R, based on investigator-assessed validated Clinical Severity Scores [Срок оценки: 48 weeks]
• The proportion of participants with at least one serious adverse event [Срок оценки: 28 weeks]
• Total number of adverse events [Срок оценки: 28 weeks]
• The cumulative corticosteroid usage [Срок оценки: 48 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Индонезия · 6 центров

• Sitanala Leprosy Hospital — Tangerang
• Palangga Health Center — Makassar
• Bajeng Health Center — Makassar
• Abe Pantai Community Health Center — Jayapura
• Hamadi Community Health Center — Jayapura
• Jayapura Utara Community Health Center — Jayapura

Публикации

• 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, controlle PMID 38808319

Идентификаторы

NCT: NCT05243654 · EOCRU.2021.002 · OXTREC 14-21

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗