Efficacy and Safety of Imatinib in Scleroderma

NCT ID: NCT00479934

Last Updated: 2011-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2010-12-31

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.

Conditions

Scleroderma, Localized; Scleroderma, Systemic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

6 month treatment with Imtinib 400mg/day

Group Type: EXPERIMENTAL

imatinib mesylate

Intervention Type: DRUG

6 month treatment with 400mg/day (per os)

2

6 month treatment with Placebo 400mg/day

Group Type: PLACEBO_COMPARATOR

imatinib mesylate

Intervention Type: DRUG

6 month treatment with 400mg/day (per os)

Interventions

imatinib mesylate

6 month treatment with 400mg/day (per os)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

University Hospital, Bordeaux

Principal Investigators

Alain TAIEB, Pr.

Role: STUDY_DIRECTOR

University Hospital, Bordeaux, France

Geneviève CHENE, Pr

Role: STUDY_CHAIR

University Hospital, Bordeaux, France

Alian TAIEB, Pr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux, France

Locations

Service de Dermatologie et services de médecine interne et vasculaire - Hôpital St André - CHU de Bordeaux

Bordeaux, , France

Service de Rhumatologie, Hôpital Pellegrin-Tondu CHU de Bordeaux

Bordeaux, , France

Service de Dermatologie - CHG Libourne

Libourne, , France

Service de dermatologie - CHU de Limoges

Limoges, , France

Service de Médecin interne - Hôpital central

Nancy, , France

Service de Médecine interne - Hôpital Saint Louis

Paris, , France

Service de Dermatologie - service de médecine interne et vasculaire - hopital haut Lévêque - av.de magellan

Pessac, , France

Service de Dermatologie - CHG Périgueux

Périgueux, , France

Service de Rhumatologie - CHU de Strasbourg

Strasbourg, , France

Service de Dermatologie - CHU de Toulouse - Hopital Purpan

Toulouse, , France

Service de Médecine interne - CHU de Tours

Tours, , France

Néphrologie et Médecine interne - CH de Valenciennes

Valenciennes, , France

Countries

France

Other Identifiers

2006/017

Identifier Type: -

Identifier Source: secondary_id

CHUBX 2006/05

Identifier Type: -

Identifier Source: org_study_id