Efficacy Study of Methotrexate to Treat Sarcoid-associated Uveitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether methotrexate is a effective corticosteroid sparing agent in the treatment of sarcoid-associated uveitis.

Detailed Description
-----------------
Macular oedema remains a significant cause of blindness. Corticosteroids are effective in the treatment of sarcoid-associated macular oedema but more than 50% of relapses occur when corticosteroids are tapered. Methotrexate (MTX) at low dose has been shown to be an effective and safe steroid-sparing agent for lung sarcoidosis and compilation of reported small series of patients with sarcoid-associated uveitis suggest that only 25% of relapses could be achieved with low dose MTX. We decide therefore to test the clinical efficacy of MTX in sarcoid-associated uveitis.

Official Title
-----------------
Corticosteroid Sparing Effect of Methotrexate in Patients With Sarcoid- Associated Uveitis: A Double Blind, Randomized, Placebo Controlled-study -UVEXATE

Conditions
-----------------
Sarcoid-associated Uveitis, Ocular Sarcoidosis, Macular Edema

Intervention / Treatment
-----------------
* Drug: Methotrexate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients over 18 years old Provided written consent for participation in the trial prior to any study-specific procedures or requirements Posterior uveitis or panuveitis associated with macular oedema defined as increased macular thickness (more than 250 mm assessed by Stratus TD-OCT or 300 mm with Cirrus SD-OCT ) and/or the presence of cystoid spaces in the macula, and the absence of epiretinal membranes. Patient with oral contraception Posterior uveitis or panuveitis associated with macular oedema Patients with histologically proven sarcoidosis or a presumed sarcoidosis. In case of a non caseating granuloma in biopsy tissues, the patients with presumed sarcoidosis meet at least 2 of the 4 following criteria: typical changes on chest radiography and computed tomography; predominantly CD4 lymphocytosis in bronchoalveolar lavage (BAL) fluid; elevated serum ACE levels; elevated gallium or 5 fluorodeoxyglucose uptake Exclusion Criteria: Patients who do not fulfill the inclusion criteria Other causes of uveitis Extra ophthalmologic manifestations of sarcoidosis justifying corticosteroids Patients previously treated with immunosuppressive agents or corticosteroids of more than 10 mg daily over 15 days. Patients with life-threatening conditions Chronic hepatopathy or renal failure Uncontrolled diabetes mellitus

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methotrexate<br> | Drug: Methotrexate<br>* All patients will receive three pulses of methylprednisolone (5 mg/kg) followed by four weeks of prednisone (1 mg/kg daily). After randomization, patients will receive either prednisone (1 mg/kg daily) plus methotrexate (0.3 mg/kg weekly) or prednisone (1 mg/kg daily) plus placebo. Therapies will be administered orally. Corticosteroids will be progressively tapered when macular oedema completely resolve. Unilateral macular oedema relapses will be treated with a single local injection triamcinolone acetonide. Increasing dose of prednisone will be administered in case of bilateral macular oedema relapses.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* All patients will receive three pulses of methylprednisolone (5 mg/kg) followed by four weeks of prednisone (1 mg/kg daily). After randomization, patients will receive either prednisone (1 mg/kg daily) plus methotrexate (0.3 mg/kg weekly) or prednisone (1 mg/kg daily) plus placebo. Therapies will be administered orally. Corticosteroids will be progressively tapered when macular oedema completely resolve. Unilateral macular oedema relapses will be treated with a single local injection of triamcinolone acetonide. Increasing dose of prednisone will be administered in case of bilateral macular oedema relapses.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of macular oedema relapses. Every two weeks for five months, the amount of macular oedema will be assessed by Optical Coherence Tomography. |  | at 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulated dose of prednisone |  | at 26 weeks | 
| Number of triamcinolone injections |  | at 26 weeks | 
| Adverse effects |  | at 26 weeks | 
| Percentage of patients with best corrected visual acuity under 0.1, 0.2 and 0. |  | at 26 weeks | 
| Percentage of patients with active anterior and /or posterior uveitis |  | at 26 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sarcoid-associated uveitis, Macular oedema, Methotrexate, Conventional corticosteroids sparing agent.