Clinical trial NCT00479934: Efficacy and Safety of Imatinib in Scleroderma
Official title: Phase II Randomized Double Blind Clinical Trial of'Imatinib Mesylate STI571 (Glivec®) Versus Placebo in Patients With Severe Cutaneous Scleroderma or Systemic Sclerosis With Severe Cutaneous Involvement.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Scleroderma, Localized
Scleroderma, Systemic
Keywords: scleroderma
imatinib
PDGFR
Rodnan
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Novartis
First posted: 2007-05-30
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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.
timeFrame: 6 month
Secondary outcomes:
measure: 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.
timeFrame: 1, 3 and 12 month
measure: Assess skin thickness at inclusion and at 6 months using skin biopsies
timeFrame: 6 month
measure: Assessment of quality of life using DLQI (Dermatology Quality of Life Index) and HAQ (Health Assessment Questionnaire).
timeFrame: At 1, 3, 6 month and 1 year,
measure: Assess tolerance of treatment (clinical and laboratory monitoring of side effects)
timeFrame: All along the trial
measure: Assess effects of treatment on non cutaneous symptoms in systemic sclerosis patients
timeFrame: All along the trial
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Service de Dermatologie et services de médecine interne et vasculaire - Hôpital St André - CHU de Bordeaux
city: Bordeaux
country: France
facility: Service de Rhumatologie, Hôpital Pellegrin-Tondu CHU de Bordeaux
city: Libourne
country: France
facility: Service de Dermatologie - CHG Libourne
city: Limoges
country: France
facility: Service de dermatologie - CHU de Limoges
city: Nancy
country: France
facility: Service de Médecin interne - Hôpital central
city: Paris
country: France
facility: Service de Médecine interne - Hôpital Saint Louis
city: Perigueux
country: France
facility: Service de Dermatologie - CHG Périgueux
city: Pessac
country: France
facility: Service de Dermatologie - service de médecine interne et vasculaire - hopital haut Lévêque - av.de magellan
city: Strasbourg
country: France
facility: Service de Rhumatologie - CHU de Strasbourg
city: Toulouse
country: France
facility: Service de Dermatologie - CHU de Toulouse - Hopital Purpan
city: Tours
country: France
facility: Service de Médecine interne - CHU de Tours
city: Valenciennes
country: France
facility: Néphrologie et Médecine interne - CH de Valenciennes
Study officials:
affiliation: University Hospital, Bordeaux, France
name: Alain TAIEB, Pr.
role: STUDY_DIRECTOR
affiliation: University Hospital, Bordeaux, France
name: Geneviève CHENE, Pr
role: STUDY_CHAIR
affiliation: University Hospital, Bordeaux, France
name: Alian TAIEB, Pr.
role: PRINCIPAL_INVESTIGATOR
References: