Use of Simvastatin as a Steroid Sparing Agent for Uveitis Patients

Study Overview
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Brief Summary
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The trial will compare the effect on disease control and immunosuppression treatment of adding simvastatin 80mg once daily, over a follow-up and treatment period of 2 years. Patients will be randomised in a 1:1 fashion to standard treatment with placebo or standard treatment with the addition of simvastatin (80mg daily). They will be followed at 3 months intervals for 2 years with a primary end point of mean reduction in corticosteroid dosage at the 12 month follow-up visit.

Detailed Description
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This is a non-commercial trial to explore the effect of simvastatin 80mg od on the dose of corticosteroids and immunosuppression in patients with sight-threatening uveitis. In order to detect a clinical effect the study is designed as a double blinded, parallel group, placebo-controlled, randomised trial. Double blinding will be achieved through the use of a placebo as well as a masked clinical assessor. Based on the reported effect of simvastatin on brain atrophy among multi[le sclerosis patients after 12 months treatment, patients will receive treatment or placebo and will be treated and followed up for 24 months. Patients randomised to simvastatin will receive a dose of 80mg od. There will be no dose escalation. Patients will be reviewed every 3 months and will undergo a complete ophthalmic examination with treatment adjustment accordingly.

Official Title
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Can Simvastatin Significantly Reduce the Amount of Immunosuppressive Medication Required by Patients With Sight Threatening Uveitis? A Phase 2b, Single Site, Randomized, Placebo Controlled, Double Blinded Trial.

Conditions
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Uveitis

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be >18 years and under 80 years. Both sexes may participate, but, because of possible teratogenicity of simvastatin women may do so only following counselling about the need for adequate contraception. Women of child bearing potential will have to have a negative pregnancy test prior to enrolment. Patients must have been previously diagnosed with intermediate, posterior or panuveitis (as defined by the standardization of uveitis nomenclature group).14 Patients must be taking systemic prednisolone 10mg once daily or more. Patients may be treated with or without a second line agent. Patients must be willing and able to provide informed consent Exclusion Criteria: No associated underlying systemic disease causing the uveitis. Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment. Females must not be breastfeeding. Patients concomitantly taking ciclosporin, fibrates, amiodarone, amlodipine, verapamil, cytochrome P450 3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole), HIV protease inhibitors (e.g. nelfinavir), erythromycin, clarithromycin, telithromycin, nefazodone, gemfibrozil, danazol, fusidic acid, diltiazem or anti-coagulants. Patients will be advised not to drink grapefruit juice during the study. Family history of hereditary muscle disorders. Active Liver disease Severe renal insufficiency. Persistently elevated serum transaminases. Allergies to excipients of simvastatin and placebo Lactose intolerance Involvement in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatine<br>Group of patients receiving simvastatin 80mg once daily in addition to standard care | Drug: Simvastatin<br>* Simvastatin 80mg once daily<br>|
| Placebo Comparator: Placebo<br>Group of patients receiving placebo once daily in addition to standard care | Drug: Placebo<br>* Placebo tablets once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Change in dose (mg) of prednisolone after 12 months of treatment | To determine whether the mean reduction in prednisolone dosage achieved at 12 months is greater in the simvastatin group compared to the placebo treated group? | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean reduction in prednisolone achieved at 24 months. |  | 24 months | 
| The chnage in the number of 2nd-line immunosuppressive drugs at 24 months |  | 24 months | 
| The number of disease relapses by 24 months |  | 24 months | 
| Blood cholesterol and lipid levels at 24 months as compared to baseline |  | 24 months | 
| Change in visual acuity at 12 and 24 months as compared to baseline |  | 12 and 24 months | 
| Treg and Th17 levels at 12 and 24 months as compared to baseline |  | 12 and 24 months | 
| Number of patients with adverse events. |  | 24 months | 
| The change in dose (mg) of 2nd-line immunosuppressive drugs at 24months |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uveitis, Simvastatin, Visual acuity, Corticosteroids, Immunosuppression