Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum

Erythema Nodosum Leprosum Clinical Trial

— MaPs  

Official title:

Methotrexate and Prednisolone Study in Erythema Nodosum Leprosum (MaPS in ENL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03775460
• Other study ID #: 15762
• Status: Recruiting
• Phase: N/A
• Start date: January 15, 2023
• Est. completion date: December 1, 2024

Study information

• Verified date: March 2023
• Source: London School of Hygiene and Tropical Medicine
• Contact: Barbara de Barros, M.D
• Phone: +44(0)2079272316
• Email: barbara.de-barros[@]lshtm.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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):

1. Individuals who diagnosed with leprosy complicated by ENL

2. Individuals with ENL aged 18-60 years old

3. Individuals with ENL deteriorating symptoms

4. Individuals with 10 or more tender, papular or nodular ENL skin lesions

5. Individuals with an EESS score of at least 9

6. Individuals with ENL on:

1. No current anti- ENL treatment

2. Prednisolone up to 30mg per day (if ACUTE) or Prednisolone 10-30mg (inclusive) per day (if RECURRENT/ CHRONIC) or equivalent alternative corticosteroid dose OR

3. Thalidomide or other non-steroidal anti-ENL medication OR

4. A combination of prednisolone (up to 30mg) and another non-steroidal anti-ENL medication (thalidomide, clofazimine, azathioprine, pentoxifylline, ciclosporin, minocycline)

Exclusion criteria:

1. Individuals who were first diagnosed with ENL more than 4 years prior to enrolment

2. Individuals less than 18 years old or older than 60 years

3. Individuals weighing less than 35kg

4. Individuals with 9 or fewer tender, popular or nodular ENL skin lesions

5. Individuals with an EESS score of 8 or less

6. 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

7. Pregnant or breastfeeding women

8. Individuals with recurrent or chronic ENL who deteriorate on a dose of prednisolone less than 10 mg or more than 30 mg

9. Individuals who have taken methotrexate by any route for the last 12 weeks

10. Individuals with a hypersensitivity to methotrexate or a recognised contraindication ( please see Methotrexate information sheet)

11. Individuals currently diagnosed with Type 1 reaction or Lucio's phenomenon

12. Individuals with the severe abnormalities in screening investigations

13. Positive serology for HIV, Hepatitis B or C

14. Evidence of tuberculosis or pulmonary fibrosis

15. A history of chronic liver disease or excessive alcohol or illicit substance consumption

16. Individuals with severe inter-current infections, uncontrolled diabetes, active peptic ulcer disease, untreated malignancy

17. Individuals unable to attend regularly for assessment or monitoring

Related Conditions & MeSH terms

• Erythema
• Erythema Nodosum Leprosum

Intervention

Drug:
• Methotrexate
Participants in the intervention group will receive methotrexate along side prednisolone
• Placebo
Participants in the control arm will receive placebo along side prednisolone
• Prednisolone
Participants in both arm will receive prednisolone, which will be the same dosage: 40 mg (initial dose) decreasing dosage for 20 weeks

Locations

Country	Name	City	State
Bangladesh	TMLI Bangladesh/ DBLM hospital	Dhaka
Brazil	FIOCRUZ	Rio De Janeiro
Ethiopia	ALERT	Addis Ababa
India	The Leprosy Mission Trust	Delhi
India	Bombay Leprosy Project	Mumbai
Indonesia	Soetomo Hospital	Surabaya
Nepal	Anandaban Hospital	Kathmandu

Sponsors (9)

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

Countries where clinical trial is conducted

Bangladesh,  Brazil,  Ethiopia,  India,  Indonesia,  Nepal, 

References & Publications (33)

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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	60 weeks
Secondary	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.	at 24 and 48 weeks
Secondary	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.	at 24 and 48 weeks
Secondary	Proportion of individuals free from ENL flares at 60 weeks	Proportion of individuals who do not require prednisolone at 60 weeks	60 weeks
Secondary	ENL flares per individual up to 60 weeks	Number of flares of ENL per individual requiring additional prednisolone up to 60 weeks	60 weeks
Secondary	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	60 weeks
Secondary	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	60 weeks
Secondary	Adverse effects	Proportion of individuals with treatment related adverse effects	60 weeks
Secondary	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	60 weeks
Secondary	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.	60 weeks
Secondary	Individuals free from ENL flares in 60 weeks	Proportion of individuals who have not required additional prednisolone in the 60 weeks of the trial	60 weeks