Pilot Study of Leflunomide for the Treatment of Uveitis
Leflunomide
Maladies oculaires+4
+ Processus pathologiques
+ Conditions pathologiques, signes et symptômes
Étude thérapeutique
Résumé
Date de début de l'étude : 1 mars 1999
Date à laquelle le premier participant a commencé l'étude.Although corticosteroids remain the mainstay of therapy for intraocular inflammation, many patients are intolerant or resistant to corticosteroid therapy. In these patients, other immunosuppressive agents have been employed to control potentially sight-threatening uveitis. Nevertheless, ideal therapy for these patients remains elusive, and there is a need for new immunosuppressive agents with varying modes of action and side effect profiles. Leflunomide, an isoxazole derivative, has profound immunosuppressive activity. Leflunomide inhibits autoimmune disease in animal models and has been used to treat patients with rheumatoid arthritis (RA). We propose a randomized masked pilot trial of leflunomide versus placebo for the treatment of uveitis. Sixteen patients 16 years of age or older with active intermediate, posterior, or panuveitis will be randomly assigned to receive prednisone and leflunomide or prednisone and placebo. Patients will then have the prednisone tapered according to a standardized schedule. The primary purpose of the study is to investigate the safety and efficacy of leflunomide versus placebo. The primary safety endpoint is the frequency of any of the following: abdominal pain, diarrhea, skin rash, hypertension, and alopecia. In addition, weight loss distributions and change in liver function tests will be described. The primary efficacy endpoint is any one or more of the following (1) a decrease of 10 or more letters in visual acuity from the baseline score for any reason, or (2) inability to taper prednisone to 10 mg qd by week 16 post randomization, or (3) inability to maintain the prednisone taper through Month 6 or Month 12, or (4) the addition of systemic therapy to treat ocular inflammatory disease. Secondary outcomes will include change in vitreous haze and presence or absence of cystoid macular edema.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.16 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
INCLUSION CRITERIA: Diagnosis of current intermediate or posterior uveitis, or panuveitis. Current evidence of active intraocular inflammation based on the presence of vitreous haze, active retinal lesions, retinal vasculitis, or cystoid macular edema. 16 years of age or older. Visual acuity of 73 letters or fewer (Snellen equivalent: 20/40 or worse) in at least one eye. The ability to understand and sign an informed consent form which must be obtained prior to randomization. The diagnosis of intermediate uveitis requires the presence of vitritis and either peripheral retinal vascular disease, cellular debris in the inferior vitreous (vitreous snowballs), exudate on the pars plana, or peripheral retinal infiltrates. The diagnosis of posterior uveitis requires the presence of infiltrative retinal lesions involving the posterior pole of the eye, usually with vitritis and often times with cystoid macular edema. The amount of cystoid macular edema will be graded by a standard protocol using Fluorescein Angiogram. The diagnosis of pan-uveitis requires the finding of active anterior segment inflammation, vitritis, and infiltrative retinal lesions. EXCLUSION CRITERIA: Ocular or systemic disease requiring greater than 1 mg/kg/day of prednisone or greater than 80 mg qd if patients weigh more than 80 kg, or requiring other systemic immunosuppressants. Periocular injections of corticosteroids within the previous 4 weeks. Intolerance or contraindications to corticosteroids. Female who is pregnant or lactating. Patient refuses to use contraception during the study and 24 months after termination of active study therapy or undergo a cholestyramine washout regimen or an activated charcoal regimen under the care of a physician following termination of study therapy, if child-bearing or fathering potential exists. Patients with Behcet's disease. Use of Latanoprost within 2 weeks prior to enrollment, or current or likely need for Latanoprost during the course of the study. Hypersensitivity to fluorescein dye. Contraindications to use of steroids at dose and schedule. SGOT (AST) or SGPT(ALT) greater than or equal to 2 times the upper limit of normal. Allergic or hypersensitivity to leflunomide or any excipients.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site
National Eye Institute (NEI)
Bethesda, United StatesOuvrir National Eye Institute (NEI) dans Google Maps