Methotrexate in the Treatment of Chronic Idiopathic Urticaria (MUCIS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University Hospital, Tours
Sponsor:
Information provided by (Responsible Party):
University Hospital, Tours
ClinicalTrials.gov Identifier:
NCT01960283
First received: January 15, 2013
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

Chronic urticaria is defined by urticarial lesions persisting at 6 weeks. The cause is not found in about 75% of cases (chronic idiopathic urticaria). The gold standard treatment consists of anti-H1 molecules. In severe cases, refractory to anti-H1, few therapeutic alternatives exist. Methotrexate, which is not expensive and often prescribed by dermatologists, has been efficiently tried in an open study on severe chronic idiopathic urticaria, and also in few case reports.


Condition Intervention Phase
Chronic Urticaria
Drug: Methotrexate (Novatrex ®) + anti-H1
Drug: Placebo + anti-H1
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial Evaluating the Efficacy of Methotrexate in Addition to Anti-H1 Versus Placebo and Anti-H1 in the Treatment of Severe Chronic Idiopathic Urticaria

Resource links provided by NLM:


Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • Number of patients with complete remission of urticaria at 18 weeks [ Time Frame: at 18 weeks of treatment ] [ Designated as safety issue: No ]
    Number of patients with complete remission of urticaria at 18 weeks, defined as no urticarial lesion 30 days before W18


Secondary Outcome Measures:
  • Tolerance : clinical and biological safety [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    Number of patients with clinical adverse effects Number of patients with biological adverse effects

  • Efficacy of the treatment in improving symptoms : pruritus [ Time Frame: 18 weeks and 26 weeks ] [ Designated as safety issue: No ]

    Number of patients with :

    - pruritus At 18 weeks and 26 weeks


  • Persistency of the complete remission at 26 weeks [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Number of patients with persistency of the complete remission, defined as no urticarial lesion from the withdrawal of treatment until W26

  • Efficacy of the treatment in improving symptoms : outbreaks by week [ Time Frame: 18 weeks and 26 weeks ] [ Designated as safety issue: No ]
    - number of outbreaks by week/patient At 18 weeks and 26 weeks

  • Efficacy of the treatment in improving symptoms : duration of lesions [ Time Frame: 18 weeks and 26 weeks ] [ Designated as safety issue: No ]
    - mean +/- standard deviation duration of lesions At 18 weeks and 26 weeks

  • Efficacy of the treatment in improving quality of life [ Time Frame: 18 weeks and 26 weeks ] [ Designated as safety issue: No ]

    Mean DLQI (quality of life) score :

    At 18 weeks and 26 weeks


  • Efficacy of the treatment in improving quality of sleep [ Time Frame: 18 weeks and 26 weeks ] [ Designated as safety issue: No ]
    Mean score of quality of sleep (from 0 to 100) At 18 weeks and 26 weeks

  • Efficacy of the treatment in improving facial/cervical urticarial lesions [ Time Frame: 18 weeks and 26 weeks ] [ Designated as safety issue: No ]

    Number of patients with, either :

    • facial/cervical urticarial lesions
    • urticarial lesions on the body only
    • facial/cervical + body lesions Indeed, facial or cervical urticarial lesions are considered more disturbing. At W18 and W26


Estimated Enrollment: 110
Study Start Date: November 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group I

The group I will receive the intervention :

Methotrexate + anti-H1

Drug: Methotrexate (Novatrex ®) + anti-H1

Methotrexate (Novatrex ®) tablets 2.5 mg methotrexate 0.2 mg/kg/week as a single dose, orally for 8 weeks.

After 8 weeks, if the treatment is still not efficient, the dose will be increased to 0.25 mg/kg/week and continued until W18.

For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and methotrexate will be added in this group.

Other Names:
  • Methotrexate
  • Anti-H1
Placebo Comparator: Group II
The intervention in group II will include : placebo + anti-H1
Drug: Placebo + anti-H1

Placebo: 0.2 mg / kg / week as a single dose, orally for 8 weeks. After eight weeks, if the patient is still very embarrassed, the dose is increased to 0.25 mg / kg / week in a weekly dose.

For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and the placebo of methotrexate will be added in this group.

Other Name: Placebo of methetrexate + anti-H1

Detailed Description:

Chronic urticaria, defined by its persistence beyond 6 weeks, is a common condition (0.1% to 3% of the general population), occurring at any age. The etiology is not found in nearly 75% of cases (chronic idiopathic urticaria). Chronic idiopathic urticaria may resolve over several months or years. The quality of life of patients is usually strongly spoiled. The gold standard treatment consist of anti-H1 molecules. In severe cases, which are refractory to anti-H1, few therapeutic alternatives exist. Two studies have shown a benefit when adding to anti-H1, montelukast, anti-leukotriene, or cyclosporine. Methotrexate, which is another immunosuppressive drug, cheap and commonly prescribed by dermatologists, has been efficient in severe chronic urticaria, in an open study and in few case reports.

Methotrexate, an anti-metabolite drug which inhibits dihydrofolate reductase, is indicated in hematologic malignancies and in autoimmune diseases. It may be given by oral or parenteral administration, once a week, and requires regular monitoring of renal and hepatic function, and blood count.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients who met the diagnostic criteria for chronic idiopathic urticaria, previously treated by

  • 3 different molecules of anti-H1 or
  • a combination of 2 different molecules of anti-H1 or
  • 1 molecule of anti-H1 with at least a double dose for a total treatment duration of ≥ 3 months before inclusion
  • With persistency of at least 7 days with urticarial lesions in the previous month

Exclusion Criteria:

  • Differential diagnosis of chronic idiopathic urticaria (urticarial vasculitis)
  • Treatment with montelukast or immunosuppressive drugs during the previous month
  • Contraindications to methotrexate

    • Allergy to methotrexate
    • Treatment which are contraindicated with methotrexate
    • Pregnancy, possibility of getting pregnant (no effective contraception), breastfeeding
    • Anomalies in liver function (transaminases or liver failure at a rate 1.5 X normal)
    • Severe renal impairment (creatinine clearance calculated by the cockcroft formula <50 ml / min)
    • Chronic respiratory failure
    • Active infectious chronic diseases (viral hepatitis, HIV)
    • History of neoplasia
    • Mental deficiency
    • Involvement in another drug clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01960283

Contacts
Contact: Mahtab SAMIMI, MD 33 2 47 47 90 80 samimi.mahtab@yahoo.fr
Contact: Christine FOULON 33 2 47 47 46 33 christine.foulon@med.univ-tours.fr

Locations
France
CHRU BREST Morvan Not yet recruiting
Brest, France, 29000
Contact: Laurent MISERY, Dr    +33(0)298223315    laurent.misery@chu-brest.fr   
Principal Investigator: Laurent MISERY, Pr         
Sub-Investigator: Anne-Marie CONTIOS-ROGUEDAS, Dr         
Sub-Investigator: Claire ABASQ, Dr         
Sub-Investigator: Nolwenn COQUART, Dr         
Sub-Investigator: Emilie BRENAUT, Dr         
Chu Mondor Recruiting
Créteil, France, 94000
Contact: Olivier CHOSIDOW, Pr    +33(0)149812501    olivier.chosidow@hmn.aphp.fr   
Sub-Investigator: Germaine GABISON, Dr         
Ch Le Mans Recruiting
Le Mans, France, 72000
Contact: Nathalie BENETON, Dr    +33(0)243434358    nbeneton@ch-lemans.fr   
Principal Investigator: Hervé MAILLARD, Dr         
Sub-Investigator: Philippe CELERIER, Dr         
Sub-Investigator: Marion FENOT, Dr         
Sub-Investigator: Corina BARA-PASSOT, Dr         
CHRU LILLE Huriez Recruiting
Lille, France, 59000
Contact: Delphine STAUMONT-SALLE, Dr    +33(0)320444193    Delphine.SALLE@CHRU-LILLE.FR   
Sub-Investigator: Emeline PAPE, Dr         
CHRU NANCY Brabois Recruiting
Nancy, France, 54000
Contact: Annick BARBAUD, Pr    +33(0)383711545    a.barbaud@chu-nancy.fr   
Sub-Investigator: Julie WATON, Dr         
Sub-Investigator: Jean-François CUNY, Dr         
Chru Nantes Recruiting
Nantes, France, 44000
Contact: Claire BERNIER, Dr    +33(0)240084116    claire.bernier@chu-nantes.fr   
Sub-Investigator: Sébastien BARBAROT, Dr         
Sub-Investigator: Hélène AUBERT, Dr         
Hopital TENON Recruiting
Paris, France, 75020
Contact: Angèle SORIA, Pr    +33(0)156017000    selim.aractingi@tnn.aphp.fr   
Sub-Investigator: Emmanuelle AMSLER, Dr         
CHRU POITIERS La Miléterie Recruiting
Poitiers, France, 86000
Contact: Gérard GUILLET, Dr    +33(0)549444400    gerard.guillet@chu-poitiers.fr   
Principal Investigator: Gérard GUILLET, Dr         
Sub-Investigator: Ewa WIERZBICKA, Dr         
Chru Reims Recruiting
Reims, France, 51000
Contact: Anne GRANGE-PRUNIER, Dr    +33(0326784367    agrange@chu-reims.fr   
Sub-Investigator: Ziad REGUAI, Dr         
Sub-Investigator: Philippe BERNARD, Dr         
CHRU RENNES Pontchaillou Recruiting
Rennes, France, 35000
Contact: Henri ADAMSKI, Dr    +33(0)299284349    henri.adamski@chu-rennes.fr   
Principal Investigator: Henri ADAMSKI, Dr         
Sub-Investigator: Alain DUPUY, Pr         
Sub-Investigator: Juliette MIQUEL, Dr         
Sub-Investigator: Catherine DROITCOURT, Dr         
Chru Tours Recruiting
Tours, France, 37044
Contact: Annabel MARUANI, Dr    +33(0)247479076    annabel.maruani@univ-tours.fr   
Principal Investigator: Annbel MARUANI, Dr         
Sub-Investigator: Laurent MACHET, Pr         
Sub-Investigator: Cyrille HOARAU, Dr         
Sub-Investigator: Mahtab SAMIMI, Dr         
Sub-Investigator: Emmanuelle LE BIDRE, Dr         
Sub-Investigator: Gabriela GEORGESCOU, Dr         
Sub-Investigator: Elodie LE FOURN, Dr         
Sponsors and Collaborators
University Hospital, Tours
Investigators
Principal Investigator: Annabel MARUANI, MD, PhD University Hospital of Tours, France
  More Information

No publications provided

Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT01960283     History of Changes
Other Study ID Numbers: PHRN09-AM/MUCIS
Study First Received: January 15, 2013
Last Updated: October 8, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014