The Efficiency Of The Methotrexate At Patients Affected By Grave Pelade (MP3)

RANDOMIZED DOUBLE-BLIND STUDY MULTICENTRIQUE TESTING THE EFFICIENCY OF the METHOTREXATE AT PATIENTS AFFECTED BY GRAVE PELADE (METHOTREXATE VERSUS PLACEBO WITH SECONDARY TREATMENT BY METHOTREXATE and PREDNISONE)

Alopecia areata (AA) is an auto immune disorder. Treatment of severe types remains difficult with a rate of hair regrowth which is lower than 10%. This RCT will assess the safety and efficacy of methotrexate alone or associated with low doses of prednisone versus placebo in the treatment of severe types of AA.

Study Overview

• Status: Completed
• Conditions: ALOPECIA AREATA
• Intervention / Treatment: Drug: Methotrexate; Drug: Placebo

Detailed Description

Background: Alopecia areata (AA) is an auto immune disorder. Chronic and severe types of AA have a major impact on patients' quality of life. Treatment of severe types of AA include phototherapy, pulse IV corticosteroids, topical immunotherapy. These treatments are poorly effective in severe types of AA, since the rate of hair regrowth remains lower than 10%. Methotrexate is an immunosuppressant which is used in many autoimmune skin disorders.

Aim: To assess the safety and efficacy of methotrexate versus placebo in the treatment of severe types of AA.

Design: Patients will be randomly assigned to receive methotrexate 20 to 25 mg / week for 6 months. Patients who will experience at least a 25% hair regrowth after 5 months will continue methotrexate or placebo from month 6 to the end of the study (month 12). Non responder patients will be re randomized to receive either methotrexate alone or associated with prednisone 0.3 mg/Kg/day from month 6 to the end of the study (month 12).

Study Design Primary outcome Rate of complete or almost complete hair regrowth at the month 12 evaluation in patients treated with methotrexate or placebo who have not been re randomized after the month 5 evaluation and have staid in their initial group of randomization Secondary outcomes

1. Rate of Global Regrowth Assesment (GRA) at month 6 and 12 .
2. Delay of hair regrowth
3. Rate of relapse
4. Quality of life
5. Safety

Arm description Arm A: methotrexate 20 to 25 mg / week for 6 months. Arm B placebo Patients who will experience at least a 25% hair regrowth after the month 5 evaluation will continue methotrexate or placebo from month 6 to the end of the study (month 12).

Non responder patients in both arms A and B will be re-randomized to receive from month 6 to the end of the study (month 12):

• methotrexate alone or
• methotrexate associated with prednisone 0.3 mg/Kg/day 10 A study population Adult patients with severe types of AA evolving without hair regrowth for at least 6 months despite previous treatments with impaired quality of life

Eligibility criteria Inclusion criteria

1. age 18 TO 70 years old
2. informed consent,
3. severe type of AA defined as : 3.1 - AA totalis universalis 3.2 - evolving for more than 6 months despite previous treatments including photothérapy (PUVA oru UVB), applications of super potent topical corticosteroid ( clobetasol propionate), applications of minoxidil 5%, or IV pulse corticosteroids 3.3 - DLQI score inferior or equal to 10

Non inclusion criteria

• Pregnant or breast feeding women
• VIH + patients
• active hepatitis B or C
• treatment with immunosuppressant (ciclosporine, mycophénolate mofetil, cyclophosphamide, azathioprine, méthotrexate) within 2 months before inclusion
• severe cardiac arythma or severe cardiac insufficiency or severe coronary disease
• liver disorder
• alcool consumption
• renal failure
• Severe diabetes mellitus
• past history of severe infection
• past history of néoplasiae ( excluding BCC),
• Karnofsky index <à 50 %
• severe lung disorder
• mental impairment
• symptomatic osteoporosis
• blood cytopénia (hémoglobine < 10 g/l ; leucocytes< 3000/mm3, platelets< 100 000/mm3)
• albuminémia < 25 g/l

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Haute Normandie
    • Rouen, Haute Normandie, France, 76031
      • Head Dermatology Department
  • Seine Maritime
    • Rouen, Seine Maritime, France, 76031
      • CHU de rouen - Hôpitaux de Rouen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. - age 18 to 70 years old
2. - informed consent,
3. - severe type of AA defined as : 3.1 - AA totalis universalis 3.2 - evolving for more than 6 months despite previous treatments including photothérapy (PUVA oru UVB), applications of super potent topical corticosteroid ( clobetasol propionate), applications of minoxidil 5%, or IV pulse corticosteroids 3.3 - DLQI score superior or equal to 10

Exclusion Criteria:

• Pregnant or breast feeding women
• VIH + patients
• active hepatitis B or C

• treatment with immunosuppressant (ciclosporine, mycophénolate mofetil

  , cyclophosphamide, azathioprine, méthotrexate) within 2 months before inclusion

• severe cardiac arythma or severe cardiac insufficiency or severe coronary disease
• liver disorder
• alcool consumption
• renal failure
• Severe diabetes mellitus
• past history of severe infection
• past history of néoplasiae ( excluding BCC),
• Karnofsky index <à 50 %
• severe lung disorder
• mental impairment
• symptomatic osteoporosis
• blood cytopénia (hémoglobine < 10 g/l ; leucocytes< 3000/mm3, platelets< 100 000/mm3)
• albuminémia < 25 g/l

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: ARM A : METHOTREXATE; Arm A: methotrexate 20 to 25 mg / week for 6 months. Patients who will experience at least a 25% hair regrowth after the month 5 evaluation will continue methotrexate or placebo from month 6 to the end of the study (month 12). Non responder patients in both arms A and B will be re-randomized to receive from month 6 to the end of the study (month 12): methotrexate alone or; methotrexate associated with prednisone 0.3 mg/Kg/day	Drug: Methotrexate; Non responder patients in arm A will be re-randomized to receive from month 6 to the end of the study (month 12): methotrexate alone or methotrexate associated with prednisone 0.3 mg/Kg/day; Other Names: Arm A: methotrexate 20 to 25 mg / week for 6 months.
Placebo Comparator: ARM B : PLACEBO; Arm B placebo Patients who will experience at least a 25% hair regrowth after the month 5 evaluation will continue methotrexate or placebo from month 6 to the end of the study (month 12). Non responder patients in both arms A and B will be re-randomized to receive from month 6 to the end of the study (month 12): methotrexate alone or; methotrexate associated with prednisone 0.3 mg/Kg/day	Drug: Placebo; Non responder patients in arm B will be re-randomized to receive from month 6 to the end of the study (month 12): methotrexate alone or methotrexate associated with prednisone 0.3 mg/Kg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OUTCOME MESURE	primary outcome Rate of complete or almost complete hair regrowth at the month 12 evaluation in patients treated with methotrexate or placebo who have not been re randomized after the month 5 evaluation and have staid in their initial group of randomization	MONTH12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SECONDARY OUTCOME MEASURE	1 Rate of Global Regrowth Assesment (GRA) at month 6 and 12 .; 2 Delay of hair regrowth; 3 Rate of relapse; 4 Quality of life; 5 Safety	MONTH 6 TO 12

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Investigators: Principal Investigator: PASCAL JOLY, PROFESSOR, CHU - Hôpitaux de Rouen

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: January 13, 2014
• First Submitted That Met QC Criteria: January 14, 2014
• First Posted (Estimate): January 15, 2014

Study Record Updates

• Last Update Posted (Actual): May 29, 2018
• Last Update Submitted That Met QC Criteria: May 25, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: ALOPECIA AREATA; TREATMENT METHOTREXATE
• Additional Relevant MeSH Terms: Skin Diseases; Pathological Conditions, Anatomical; Hypotrichosis; Hair Diseases; Alopecia; Alopecia Areata; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: 2011/121/HP