Back to resultsMethotrexate and Prednisolone Study in Erythema Nodosum Leprosum (MaPs)
Primary Purpose
Erythema Nodosum Leprosum
Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Methotrexate
Placebo
Prednisolone
Sponsored by
About this trial
This is an interventional treatment trial for Erythema Nodosum Leprosum focused on measuring Erythema Nodosum Leprosum, ENL, corticosteroids, Methotrexate, ENL severity scale, quality of life, Leprosy
Eligibility Criteria
Inclusion Criteria:: ALL OF THE FOLLOWING SIX CRITERIA MUST BE MET IN ORDER FOR AN INDIVIDUAL TO BE ELIGIBLE (ONLY ONE OF 6A TO 6D NEED BE MET):
- 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)
Exclusion criteria:
- 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
- Individuals with severe inter-current infections, uncontrolled diabetes, active peptic ulcer disease, untreated malignancy
- Individuals unable to attend regularly for assessment or monitoring
Sites / Locations
- TMLI Bangladesh/ DBLM hospital
- FIOCRUZ
- ALERT
- The Leprosy Mission TrustRecruiting
- Bombay Leprosy ProjectRecruiting
- Soetomo Hospital
- Anandaban Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
control
intervention
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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
Secondary Outcome Measures
Change in ENLIST ENL severity scale score (EESS)
ENLIST group (Erythema Nodosum Leprosum International STudy) developed and validated a severity scale for ENL, which consist 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the change in ENLIST ENL Severity Scale score from baseline to the first flare of ENL requiring additional prednisolone
Quality of life changes: 36- Item Short Form (SF-36) questionnaire
Change in patient reported health-related quality of life at 24 and 48 weeks from baseline. This will be measured by 36- Item Short Form (SF-36) questionnaire developed by RAND, validated worldwide. The SF-36 consists of 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. If the score is 0 is equivalent to maximum disability. The 8 sections are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, emotional role functioning, social role functioning and mental health.
Quality of life changes regarding skin condition: Dermatology life quality Index (DLQI)
Change in patient reported health-related quality of life at 24 and 48 weeks, specific to skin condition, such as ENL. It will be used the Dermatology life quality Index (DLQI),which is a questionnaire of 10 questions to specific evaluate quality of life in dermatologic conditions.The score can range from 0 to 30, meaning 0 no effect at all on patient's life to 30 extremely large effect on patient's life.
Proportion of individuals free from ENL flares at 60 weeks
Proportion of individuals who do not require prednisolone at 60 weeks
ENL flares per individual up to 60 weeks
Number of flares of ENL per individual requiring additional prednisolone up to 60 weeks
Severity of ENL flares
As stated on outcome 3, the severity of ENL will be measured by ENLIST ENL severity scale. The scale is composed by 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the maximum severity of flares of ENL requiring additional prednisolone up to 60 weeks
Time to the first flare of ENL
How long it takes to a participant who has an ENL flare to present with first episode of flare after enrolment
Adverse effects
Proportion of individuals with treatment related adverse effects
Quality of life at 60 weeks: SF-36 questionnaire
As described on outcome 4. We will use SF-36 questionnaire to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline
Quality of life at 60 weeks regarding skin condition: Dermatology Life Quality Index (DLQI) questionnaires
As described on outcome 5. We will use DLQI questionnaires to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline, specific to skin conditions such as ENL.
Individuals free from ENL flares in 60 weeks
Proportion of individuals who have not required additional prednisolone in the 60 weeks of the trial
Full Information
NCT ID
NCT03775460
First Posted
November 29, 2018
Last Updated
March 10, 2023
Sponsor
London School of Hygiene and Tropical Medicine
Collaborators
Dr. Soetomo General Hospital, The Leprosy Mission Trust, India, Alert Hospital, Ethiopia, The Leprosy Mission Bangladesh, Bombay Leprosy Project, India, Oswaldo Cruz Foundation, Leprosy Research Initiative, The Leprosy Mission Nepal
1. Study Identification
Unique Protocol Identification Number
NCT03775460
Brief Title
Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum
Acronym
MaPs
Official Title
Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum (MaPS in ENL
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 15, 2023 (Actual)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
London School of Hygiene and Tropical Medicine
Collaborators
Dr. Soetomo General Hospital, The Leprosy Mission Trust, India, Alert Hospital, Ethiopia, The Leprosy Mission Bangladesh, Bombay Leprosy Project, India, Oswaldo Cruz Foundation, Leprosy Research Initiative, The Leprosy Mission Nepal
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
This is a double blind randomized controlled trial (RCT) to test the efficacy of MTX for managing ENL. Patients diagnosed with moderate or severe ENL at ENLIST Group centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal will be randomly allocated to receive a 15 or 20 mg of oral MTX each week for 48 weeks and prednisolone 40 mg per day reducing to zero over 20 weeks. The control group will receive an identical prednisolone scheme. The participants will be stratified into two groups, those with acute ENL, those with chronic/recurrent ENL. The interventions for both populations are the same, although analysed separately. Adverse effects (AE) will be closely monitored clinically and using laboratory tests. Participants will receive folic acid, 5mg daily for 52 weeks except on the day of MTX to prevent AEs, and nausea will be managed with ondansetron.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Erythema Nodosum Leprosum
Keywords
Erythema Nodosum Leprosum, ENL, corticosteroids, Methotrexate, ENL severity scale, quality of life, Leprosy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
550 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
control
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
intervention
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Participants in the intervention group will receive methotrexate along side prednisolone
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants in the control arm will receive placebo along side prednisolone
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
Participants in both arm will receive prednisolone, which will be the same dosage: 40 mg (initial dose) decreasing dosage for 20 weeks
Primary Outcome Measure Information:
Title
Proportion of individuals free from Erythema Nodosum Leprosum (ENL) flares in 24 weeks
Description
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.
Time Frame
During the first 24 weeks
Title
Proportion of individuals free from ENL flares in 48 weeks
Description
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
Time Frame
During first 48 weeks
Secondary Outcome Measure Information:
Title
Change in ENLIST ENL severity scale score (EESS)
Description
ENLIST group (Erythema Nodosum Leprosum International STudy) developed and validated a severity scale for ENL, which consist 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the change in ENLIST ENL Severity Scale score from baseline to the first flare of ENL requiring additional prednisolone
Time Frame
60 weeks
Title
Quality of life changes: 36- Item Short Form (SF-36) questionnaire
Description
Change in patient reported health-related quality of life at 24 and 48 weeks from baseline. This will be measured by 36- Item Short Form (SF-36) questionnaire developed by RAND, validated worldwide. The SF-36 consists of 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. If the score is 0 is equivalent to maximum disability. The 8 sections are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, emotional role functioning, social role functioning and mental health.
Time Frame
at 24 and 48 weeks
Title
Quality of life changes regarding skin condition: Dermatology life quality Index (DLQI)
Description
Change in patient reported health-related quality of life at 24 and 48 weeks, specific to skin condition, such as ENL. It will be used the Dermatology life quality Index (DLQI),which is a questionnaire of 10 questions to specific evaluate quality of life in dermatologic conditions.The score can range from 0 to 30, meaning 0 no effect at all on patient's life to 30 extremely large effect on patient's life.
Time Frame
at 24 and 48 weeks
Title
Proportion of individuals free from ENL flares at 60 weeks
Description
Proportion of individuals who do not require prednisolone at 60 weeks
Time Frame
60 weeks
Title
ENL flares per individual up to 60 weeks
Description
Number of flares of ENL per individual requiring additional prednisolone up to 60 weeks
Time Frame
60 weeks
Title
Severity of ENL flares
Description
As stated on outcome 3, the severity of ENL will be measured by ENLIST ENL severity scale. The scale is composed by 10 symptoms and signs of ENL and range from 0 to 30 points. Mild ENL is categorised as an score of 8 or less. We will measure the maximum severity of flares of ENL requiring additional prednisolone up to 60 weeks
Time Frame
60 weeks
Title
Time to the first flare of ENL
Description
How long it takes to a participant who has an ENL flare to present with first episode of flare after enrolment
Time Frame
60 weeks
Title
Adverse effects
Description
Proportion of individuals with treatment related adverse effects
Time Frame
60 weeks
Title
Quality of life at 60 weeks: SF-36 questionnaire
Description
As described on outcome 4. We will use SF-36 questionnaire to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline
Time Frame
60 weeks
Title
Quality of life at 60 weeks regarding skin condition: Dermatology Life Quality Index (DLQI) questionnaires
Description
As described on outcome 5. We will use DLQI questionnaires to measure quality of life. Change in patient reported health-related quality of life at 60 weeks from baseline, specific to skin conditions such as ENL.
Time Frame
60 weeks
Title
Individuals free from ENL flares in 60 weeks
Description
Proportion of individuals who have not required additional prednisolone in the 60 weeks of the trial
Time Frame
60 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:: ALL OF THE FOLLOWING SIX CRITERIA MUST BE MET IN ORDER FOR AN INDIVIDUAL TO BE ELIGIBLE (ONLY ONE OF 6A TO 6D NEED BE MET):
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)
Exclusion criteria:
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
Individuals with severe inter-current infections, uncontrolled diabetes, active peptic ulcer disease, untreated malignancy
Individuals unable to attend regularly for assessment or monitoring
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara de Barros, M.D
Phone
+44(0)2079272316
Email
barbara.de-barros@lshtm.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Walker, MD, PhD
Organizational Affiliation
London School of Hygiene and Tropical Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
TMLI Bangladesh/ DBLM hospital
City
Dhaka
Country
Bangladesh
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Jewel Rozario
Facility Name
FIOCRUZ
City
Rio De Janeiro
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose' Nery
Facility Name
ALERT
City
Addis Ababa
Country
Ethiopia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Saba Lambert
Facility Name
The Leprosy Mission Trust
City
Delhi
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joydeepa Darlong
Facility Name
Bombay Leprosy Project
City
Mumbai
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vivek Pai
Facility Name
Soetomo Hospital
City
Surabaya
Country
Indonesia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Medhi Alinda
Facility Name
Anandaban Hospital
City
Kathmandu
Country
Nepal
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deanna Hagge
12. IPD Sharing Statement
Plan to Share IPD
No
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Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum
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