Clinical trial NCT02252328: Use of Simvastatin as a Steroid Sparing Agent for Uveitis Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Uveitis
Keywords: Uveitis
Simvastatin
Visual acuity
Corticosteroids
Immunosuppression
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2014-09-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients must be \>18 years and under 80 years.
2. Both sexes may participate, but, because of possible teratogenicity of simvastatin women may do so only following counselling about the need for adequate contraception.
3. Women of child bearing potential will have to have a negative pregnancy test prior to enrolment.
4. Patients must have been previously diagnosed with intermediate, posterior or panuveitis (as defined by the standardization of uveitis nomenclature group).14
5. Patients must be taking systemic prednisolone 10mg once daily or more.
6. Patients may be treated with or without a second line agent.
7. Patients must be willing and able to provide informed consent

Exclusion Criteria:

1. No associated underlying systemic disease causing the uveitis.
2. 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.
3. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment.
4. Females must not be breastfeeding.
5. 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.
6. Patients will be advised not to drink grapefruit juice during the study.
7. Family history of hereditary muscle disorders.
8. Active Liver disease
9. Severe renal insufficiency.
10. Persistently elevated serum transaminases.
11. Allergies to excipients of simvastatin and placebo
12. Lactose intolerance
13. Involvement in other clinical trials

Primary outcomes:
measure: 1. Change in dose (mg) of prednisolone after 12 months of treatment
timeFrame: 12 months
Secondary outcomes:
measure: The mean reduction in prednisolone achieved at 24 months.
timeFrame: 24 months
measure: The chnage in the number of 2nd-line immunosuppressive drugs at 24 months
timeFrame: 24 months
measure: The number of disease relapses by 24 months
timeFrame: 24 months
measure: Blood cholesterol and lipid levels at 24 months as compared to baseline
timeFrame: 24 months
measure: Change in visual acuity at 12 and 24 months as compared to baseline
timeFrame: 12 and 24 months
measure: Treg and Th17 levels at 12 and 24 months as compared to baseline
timeFrame: 12 and 24 months
measure: Number of patients with adverse events.
timeFrame: 24 months
measure: The change in dose (mg) of 2nd-line immunosuppressive drugs at 24months
timeFrame: 24 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
Study officials:
affiliation: University College, London
name: Oren Tomkins-Netzer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University College, London
name: Sue Lightman, PhD,FRCOphth
role: STUDY_CHAIR
References:
citation: Chataway J, Schuerer N, Alsanousi A, Chan D, MacManus D, Hunter K, Anderson V, Bangham CR, Clegg S, Nielsen C, Fox NC, Wilkie D, Nicholas JM, Calder VL, Greenwood J, Frost C, Nicholas R. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014 Jun 28;383(9936):2213-21. doi: 10.1016/S0140-6736(13)62242-4. Epub 2014 Mar 19.