Topical Steroids Alone or Associated With Methotrexate in Bullous Pemphigoid (BP/MTX)

April 21, 2026 updated by: University Hospital, Montpellier

Comparison of Monotherapy With Protracted Superpotent Topical Steroids to Superpotent Topical Steroids Associated With Methotrexate in Bullous Pemphigoid

This controlled multi-center randomized clinical trial, with direct individual benefit, will compare efficacy and safety of two strategies in non-localized BP care: a combined regimen using initial superpotent topical steroids associated with methotrexate for 4 weeks followed by methotrexate alone for 8 months and superpotent topical steroids alone maintained 9 months (current standard of care). The expected result is an equivalence between the two compared strategies in terms of safety and efficacy, MTX monotherapy during the maintenance phase being easier to manage and therefore associated with better compliance than topical steroids with less cutaneous side effects and most cost-effective.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Bullous pemphigoid (BP) is a rare mucocutaneous autoimmune bullous disorder (incidence <1/10000 / year in France) that mostly affects elderly patients. Its mortality rate is as high as 20 to 40% at one year. A study initiated by the French group for bulllous disorders devoted to the study of autoimmune bullous diseases the study of autoimmune bullous diseases and which is an international leader on this issue, has previously demonstrated the efficacy and relatively good tolerance of superpotent topical corticosteroids in BP.However, the use of superpotent topical corticosteroids is flawed with practical difficulties (home-based care by nurses once or twice a day to administer treatment, this for several months) and its cost is significantly higher than that an oral steroid treatment as a consequence. On the other hand, there is probably a non-negligible systemic absorption of superpotent topicalsteroid responsible for potentially serious side effects similar to those encountered with systemic corticosteroids. Finally, a protracted treatment with superpotent topical steroid most often causes skin atrophy with deleterious consequences.It would then be of interest to be able to significantly reduce the duration of use of topical steroids through an early-associated systemic treatment relying on an easy-to-use and relatively safe molecule that would maintain the disease under control after an initial clinical remission has been achieved by initial and time-limited use of superpotent topical steroids. Methotrexate (MTX) could be an interesting candidate in this regard, with a low-level and tolerable short- and middle-term toxicity if small doses are used (10-15 mg / week) while its long-term safety is usually irrelevant in elderly patients. Its use and monitoring are relatively easy and a number of international publications, including two recent French ones, have shown efficacy in this setting including a relaying strategy after initial use of superpotent topical steroids in BP treatment, in preliminary open studies .These encouraging results prompt to propose a controlled multi-center randomized clinical trial, with direct individual benefit, comparing efficacy and safety of a treatment regimen using superpotent topical steroids alone maintained 9 months (current standard of care) to a mixed initial treatment combining applications of superpotent topical steroids associated with methotrexate for 4 weeks followed by methotrexate alone for 8 additional months in non-localized BP. In both arms, the total treatment duration will then be 9 months. The two arms of the study will be:Arm A: daily applications of topical clobetasol propionate at a dose of 10 to 30 g / day depending on the patient's weight and the initial number of new blisters per day, associated with methotrexate (MTX) received either orally or subcutaneously at a dose of 12.5 mg / week in patients weighing less than 60 kg and with creatinine clearance greater than 50 ml / min (planned dose reduction to 10 mg / week in patients less than 60 kg or with a creatinine clearance less than 50 ml / min) for four weeks followed by oral or subcutaneous methotrexate alone at the same dose during following 8 monthsArm B: daily applications of topical clobetasol propionate at a dose of 10 to 30 g / day depending on the patient's weight and the initial number of new blisters per day maintained until 14 days after full disease control followed by the same daily dose applied every other day for a month and then twice a week for a month and then once a week until the end of the 9th month.The primary endpoint will be the actuarial survival rate at one year in both groups and secondary endpoints will be the initial control rate of the disease, the number of serious side effects during treatment and the number of relapses during treatment.The expected result is an equivalence between the two compared strategies in terms of safety and efficacy, MTX monotherapy during the maintenance phase being easier to manage and therefore associated with better compliance than topical steroids with less cutaneous side effects and most cost-effective.This study will enroll 150 patients per arm and will include a follow up of 9 months with 9 visits per patient.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
322

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Montpellier, France, 34295
        • University hospital of Montpellier

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects aged 18 years old or more
  • Patients affiliated to social security system,
  • Bullous pemphigoid diagnosed according to the following criteria: presence of at least 3 of the 4 clinical criteria for bullous pemphigoid as published by the french group for study of blistering diseases (positive predictive value: 95 %: age over 70 years, no lesions on neck or head, absence of atrophic scars, no mucosal lesions.= Histological Examination consistent with BP diagnosis and carried out in the month before inclusion: existence of a sub epidermal blister regardless of its size, containing neutrophils and / or eosinophils associated with a dermal infiltrate consisting of neutrophils and / or eosinophils, or to margination of neutrophils and / or eosinophils along the dermoepidermal junction.= Direct immunofluorescence performed (DIF) in the month preceding inclusion and showing linear deposition of IgG and / or C3 along the dermo-epidermal junction.
  • Patients: = no prior topical steroid or superpotent topical steroids for less than 16 days using the same or equivalent dosage as the one used in the study a different regimen and this regardless of the clinical resultsOR receiving potent or superpotent topical steroids for at least 16 days with a different regimen than that used during the trial AND not controlled by this treatment (appearance of at least 3 new blisters per day)
  • written consent of the patient or, if not possible, certified by a third party,
  • effective contraception (oral or intrauterine device) set up at least one month before inclusion for women of childbearing age,
  • For women of reproductive age (age <50 years), negative serum pregnancy test at inclusion
  • Serum albumin ≥ 25 g / L

Exclusion Criteria:

  • Localized bullous pemphigoid (area <400 cm2: 20 x 20 cm)
  • Major blood cytopenia: Hb ≤ 10 g / dl and / or leukocytes ≤ 3000 / mm3 and / or platelets ≤ 100,000 / mm3
  • Creatinine Clearance appreciated by the formula MDRD <30 ml / min
  • Serum albumin <25 g / L
  • pregnancy-associated Pemphigoid
  • Linear IgA Dermatosis identified by DIF
  • Pemphigoid with clinically dominant mucosal lesions
  • Relapse of previously diagnosed pemphigoid and still receiving treatment or for whom treatment was stopped for less than six months
  • Known allergy to topical steroids and / or methotrexate
  • recent history of liver disease (within two years) regardless of its nature or presence of active liver disease (transaminases and / or alkaline phosphatase greater than twice the upper standard laboratory)
  • Chronic alcoholism (declared consumption of more than 60 g alcohol / day or approximately 0.5 L / day of wine)
  • patient receiving notoriously hepatotoxic drugs or that can interfere with metabolism or haematological toxicity of Methotrexate
  • Peptic ulcer proven by endoscopy performed during the last 15 days
  • Severe Active infection regardless of its nature
  • Evolutive neoplasia whatever its nature except basal cell carcinoma
  • Poorly controlled diabetes mellitus (fasting glucose greater than or equal to 2 2.5 g / L and / or Hb A1C greater than or equal to 8.5% before treatment)
  • disease that can not be possibly monitored on a regular basis
  • acquired or congénital Immunosuppression
  • known HIV Seropositivity
  • Chronic respiratory failure
  • Pregnancy or breastfeeding
  • Patient of childbearing age and not using effective contraception
  • Patient incapable of giving informed consent and for whom a family member or a trustworthy third party does not grant participation in the study, protected adults, vulnerable people (art. L1121-6, L1121-7, L 1121-8, L1121-9) or patient accrued in another clinical research study
  • Long-term treatment prescribed for another illness by steroids, immunosuppressive drugs, cyclosporin or any other treatment that may have been successfully used in the treatment of bullous pemphigoid (dapsone, Gamma globulins, plasma exchange, tetracyclines). For all previous medications, a minimum clearance of two months is required before enrollment in the present trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A
Superpotent topical steroids/methotrexate
Drug: clobetasol propionate + Methotrexate
daily applications of topical clobetasol propionate at a dose of 10 to 30 g / day depending on the patient's weight and the initial number of new blisters per day, associated with methotrexate (MTX) received either orally or subcutaneously at a dose of 12.5 mg / week in patients weighing less than 60 kg and with creatinine clearance greater than 50 ml / min (planned dose reduction to 10 mg / week in patients less than 60 kg or with a creatinine clearance less than 50 ml / min) for four weeks followed by oral or subcutaneous methotrexate alone at the same dose during following 8 months
Other: B
Superpotent topical steroids (clobetasol propionate)
Drug: clobetasol propionate alone
daily applications of topical clobetasol propionate at a dose of 10 to 30 g / day depending on the patient's weight and the initial number of new blisters per day, up to 14 days after control of the disease followed by 1 application every 2 days at the same dose for 4 weeks then an application twice a week for 4 weeks then once application a week until the end of the 9th month of treatment

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
actuarial survival
Time Frame: 9 months
The primary endpoint is the actuarial survival rate with or without recurrence at 9 months in the topical steroid + methotrexate group (Arm A) compared to exclusive topical steroid group (Arm B).
9 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Initial control rate of the disease
Time Frame: 9 months
The initial control rate of the disease at D28 (Visit 4)
9 months
Safety: The frequency of serious and significant adverse events
Time Frame: 9 months
9 months
Frequency of relapses
Time Frame: 9 months
The frequency of relapses during treatment
9 months
Relapse-free survival
Time Frame: 9 months
relapse-free survival
9 months
Easiness of use
Time Frame: 9 months
Easiness of use indirectly estimated by treatment complicance evaluation
9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Montpellier

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Olivier Dereure, MD, PhD, University of Montpellier France; French Society of Dermatology; french group for study of blistering diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 22, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 26, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 8, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 10, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 7850

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