Efficacy and Safety of Imatinib in Scleroderma
- Conditions
- Scleroderma, LocalizedScleroderma, Systemic
- Interventions
- Registration Number
- NCT00479934
- Lead Sponsor
- University Hospital, Bordeaux
- Brief Summary
In vitro studies have shown that imatinib 1mM inhibits strongly the growth of cutaneous fibroblasts. The hypothesis is that imatinib inhibits PDGFR which is known to be a potential target for the molecule, as recently also proposed after the discovery of autoantibodies activating the PDGF receptors. Recent data indicate that TGFb is also a potential target of imatinib. Cutaneous scleroderma is characterized by progressive cutaneous fibrosis caused by hyperactive dermal fibroblasts. Since no established treatment for skin sclerosis in scleroderma is currently available. This study will test the safety and efficacy of imatinib in the treatment of patients with scleroderma and severe cutaneous involvement.
- Detailed Description
This study will test the efficacy and tolerance of patients with a high score of induration (modified Rodnan score \> 20/54) Comparison : 34 patients with severe forms of cutaneous involvement will be evaluated in a double blind RCT comparing imatinib 400mg/j and placebo in a 6 month period. Efficacy will be assessed using a cutaneous induration scale and skin biopsy, and quality of life questionnaires.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
- More than 18 years old
- Documented diagnostic of scleroderma (systemic or cutaneous)
- Severe cutaneous sclerodermia or systemic sclerodermia with m-Rodnan score > 20/51
- Ejection fraction of more than 45 per cent at cardiac ultrasound pre-inclusion study
- Woman with efficient contraceptive method during trail treatment and during 3 month after the end of trial treatment
- All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to enrolment
- Affiliated or profit patient of a social security system
- Signed informed consent
- new systemic treatment, potentially interfering with disease progression, beginning 3 months prior the start trial treatment
- Patient with isolated cutaneous scleroderma treated with a drug potentially interfering with the course of the disease 4 weeks before starting the trial (Systemic corticosteroids, methotrexate, cyclophosphamide, bosentan)
- Scleroderma " en coup de sabre "
- Severe organ failure or anomaly of blood chemistry/hematology (bilirubin, SGOT, SGPT, creatinine > 1,5 ´ upper normal limit, polymorphonuclear granulocytes less than 1*10*9/l or platelets less than 50*10*9/l),
- Ongoing cancer
- Ejection fraction ≤ 45 per cent at cardiac ultrasound pre inclusion study
- myocardial infarction of less than 6 mois at pre inclusion visit
- Non controlled chronic illness (diabetes, chronic kidney failure, chronic hepatitis, HIV infection),
- Major surgery less than two weeks before inclusion
- Pregnancy or lactation
- Absence of validated contraception in childbearing women.
- Contraindication to imatinib mesylate treatment as specified in product specifications
- Non observance anticipated and absence of informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 imatinib mesylate 6 month treatment with Placebo 400mg/day 1 imatinib mesylate 6 month treatment with Imtinib 400mg/day
- Primary Outcome Measures
Name Time Method Compare the efficacy of imatinib mesylate vs placebo based on the percent variation of modified Rodnan score (0-51) between inclusion and 6-month visits. 6 month
- Secondary Outcome Measures
Name Time Method Compare efficacy of imatinib mesylate vs placebo based on the percent variation of modified Rodnan score between the inclusion and the various time points of follow-up. 1, 3 and 12 month Assess skin thickness at inclusion and at 6 months using skin biopsies 6 month Assessment of quality of life using DLQI (Dermatology Quality of Life Index) and HAQ (Health Assessment Questionnaire). At 1, 3, 6 month and 1 year, Assess tolerance of treatment (clinical and laboratory monitoring of side effects) All along the trial Assess effects of treatment on non cutaneous symptoms in systemic sclerosis patients All along the trial
Trial Locations
- Locations (12)
Service de Rhumatologie - CHU de Strasbourg
🇫🇷Strasbourg, France
Service de Dermatologie - CHG Libourne
🇫🇷Libourne, France
Service de dermatologie - CHU de Limoges
🇫🇷Limoges, France
Service de Dermatologie - CHG Périgueux
🇫🇷Perigueux, France
Service de Rhumatologie, Hôpital Pellegrin-Tondu CHU de Bordeaux
🇫🇷Bordeaux, France
Service de Dermatologie et services de médecine interne et vasculaire - Hôpital St André - CHU de Bordeaux
🇫🇷Bordeaux, France
Service de Dermatologie - service de médecine interne et vasculaire - hopital haut Lévêque - av.de magellan
🇫🇷Pessac, France
Néphrologie et Médecine interne - CH de Valenciennes
🇫🇷Valenciennes, France
Service de Médecin interne - Hôpital central
🇫🇷Nancy, France
Service de Médecine interne - Hôpital Saint Louis
🇫🇷Paris, France
Service de Dermatologie - CHU de Toulouse - Hopital Purpan
🇫🇷Toulouse, France
Service de Médecine interne - CHU de Tours
🇫🇷Tours, France