Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum

NCT03775460 | Active Not Recruiting DMC

• 1 other identifier: 15762
• Study Type: interventional
• Target: 550
• Locations: 6 countries
• Sites: 7

Brief Summary

Erythema Nodosum Leprosum (ENL) is a painful, debilitating complication of leprosy. Patients often require high doses of corticosteroids for prolonged periods. Thalidomide is expensive and not available in most countries. The use of corticosteroids for long periods is associated with adverse effects and mortality. It is a priority to identify alternative agents to treat ENL. Methotrexate (MTX) is a cheap, widely used medication which has been reported to be effective in ENL resistant to steroids and thalidomide.

Conditions

Erythema Nodosum Leprosum

Keywords

Erythema Nodosum Leprosum; ENL; corticosteroids; Methotrexate; ENL severity scale; quality of life; Leprosy

Outcome Measures

Primary Outcomes (2)

• Proportion of individuals free from Erythema Nodosum Leprosum (ENL) flares in 24 weeks

  Proportion of individuals who have not required additional prednisolone during the first 24 weeks. The aim is to evaluate if individuals in the methotrexate regimen will need less prednisolone than the control arm.

  During the first 24 weeks

• Proportion of individuals free from ENL flares in 48 weeks

  Proportion of individuals who have not required additional prednisolone during the first 48 weeks. To evaluate if methotrexate will be more efficient to control ENL than only prednisolone

  During first 48 weeks

Secondary Outcomes (11)

• Change in ENLIST ENL severity scale score (EESS)

  60 weeks

• Quality of life changes: 36- Item Short Form (SF-36) questionnaire

  at 24 and 48 weeks

• Quality of life changes regarding skin condition: Dermatology life quality Index (DLQI)

  at 24 and 48 weeks

• Proportion of individuals free from ENL flares at 60 weeks

  60 weeks

• ENL flares per individual up to 60 weeks

  60 weeks

Study Arms (2)

control

PLACEBO COMPARATOR

Participants will receive placebo+ prednisolone. Participants will start receiving 4 dummy tablets per week, than participants weighing less than 60 kg will receive 6 dummy tablets from week 8. The placebo will be prescribe weekly. Participants weighing 60 kg or more will receive 8 dummy tablets from week 8. Participants will receive dummy tablets for 52 weeks. Along with prednisolone. The start dose of prednisolone will be 40 mg per day decreasing dosage for 20 weeks.

Drug: Placebo; Drug: Prednisolone

intervention

EXPERIMENTAL

Participants will receive Methotrexate(MTX)+prednisolone. All participants in intervention arm will receive an initial dose of MTX 10 mg. The MTX will be increased to 15 mg the following week. Participants weighing less than 60 kg will continue to receive 15 mg of MTX weekly thereafter. Individuals weighing 60 kg or more will receive MTX 20 mg from week 8. At week 48 the MTX will be reduced to 10 mg for two weeks followed by 5 mg for two weeks and then stopped. In total participants will receive 52 weeks of MTX along side prednisolone, which will be the same as the control arm.

Drug: Methotrexate; Drug: Prednisolone

Interventions

Methotrexate DRUG

Participants in the intervention group will receive methotrexate along side prednisolone

intervention

Placebo DRUG

Participants in the control arm will receive placebo along side prednisolone

control

Prednisolone DRUG

Participants in both arm will receive prednisolone, which will be the same dosage: 40 mg (initial dose) decreasing dosage for 20 weeks

control; intervention

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals who diagnosed with leprosy complicated by ENL
• Individuals with ENL aged 18-60 years old
• Individuals with ENL deteriorating symptoms
• Individuals with 10 or more tender, papular or nodular ENL skin lesions
• Individuals with an EESS score of at least 9
• Individuals with ENL on:
• No current anti- ENL treatment
• Prednisolone up to 30mg per day (if ACUTE) or Prednisolone 10-30mg (inclusive) per day (if RECURRENT/ CHRONIC) or equivalent alternative corticosteroid dose OR
• Thalidomide or other non-steroidal anti-ENL medication OR
• A combination of prednisolone (up to 30mg) and another non-steroidal anti-ENL medication (thalidomide, clofazimine, azathioprine, pentoxifylline, ciclosporin, minocycline)

You may not qualify if:

• Individuals who were first diagnosed with ENL more than 4 years prior to enrolment
• Individuals less than 18 years old or older than 60 years
• Individuals weighing less than 35kg
• Individuals with 9 or fewer tender, popular or nodular ENL skin lesions
• Individuals with an EESS score of 8 or less
• Women of child bearing capacity who decline to use two forms of adequate contraception and men who decline to use two forms of adequate contraception
• Pregnant or breastfeeding women
• Individuals with recurrent or chronic ENL who deteriorate on a dose of prednisolone less than 10 mg or more than 30 mg
• Individuals who have taken methotrexate by any route for the last 12 weeks
• Individuals with a hypersensitivity to methotrexate or a recognised contraindication ( please see Methotrexate information sheet)
• Individuals currently diagnosed with Type 1 reaction or Lucio's phenomenon
• Individuals with the severe abnormalities in screening investigations
• Positive serology for HIV, Hepatitis B or C
• Evidence of tuberculosis or pulmonary fibrosis
• A history of chronic liver disease or excessive alcohol or illicit substance consumption

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Dr. Soetomo General Hospital: collaborator
• The Leprosy Mission Trust, India: collaborator
• Alert Hospital, Ethiopia: collaborator
• The Leprosy Mission Bangladesh: collaborator
• Bombay Leprosy Project, India: collaborator
• Oswaldo Cruz Foundation: collaborator
• Leprosy Research Initiative: collaborator
• The Leprosy Mission Nepal: collaborator

Study Sites (7)

TMLI Bangladesh/ DBLM hospital

Dhaka, Bangladesh

Location

FIOCRUZ

Rio de Janeiro, Brazil

Location

ALERT

Addis Ababa, Ethiopia

Location

The Leprosy Mission Trust

Delhi, India

Location

Bombay Leprosy Project

Mumbai, India

Location

Soetomo Hospital

Surabaya, Indonesia

Location

Anandaban Hospital

Kathmandu, Nepal

Location

Related Publications (33)

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MeSH Terms

Conditions

Leprosy

Interventions

Methotrexate; Prednisolone

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Stephen Walker, MD, PhD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 14, 2018
• Study Start: January 15, 2023
• Primary Completion: September 1, 2025
• Study Completion: October 1, 2025
• Last Updated: September 10, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ET (1); IN (2); NE (1); BR (1); BA (1); ID (1)