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Use of Simvastatin as a Steroid Sparing Agent for Uveitis Patients

Primary Purpose

Uveitis

Status

Unknown status

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Simvastatin

Placebo

About this trial

This is an interventional treatment trial for Uveitis focused on measuring Uveitis, Simvastatin, Visual acuity, Corticosteroids, Immunosuppression

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Moorfields Eye Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Simvastatine

Placebo

Arm Description

Group of patients receiving simvastatin 80mg once daily in addition to standard care

Group of patients receiving placebo once daily in addition to standard care

Outcomes

Primary Outcome Measures

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?

Secondary Outcome Measures

The mean reduction in prednisolone achieved at 24 months.

The chnage in the number of 2nd-line immunosuppressive drugs at 24 months

The number of disease relapses by 24 months

Blood cholesterol and lipid levels at 24 months as compared to baseline

Change in visual acuity at 12 and 24 months as compared to baseline

Treg and Th17 levels at 12 and 24 months as compared to baseline

Number of patients with adverse events.

The change in dose (mg) of 2nd-line immunosuppressive drugs at 24months

Full Information

NCT ID

NCT02252328

First Posted

September 8, 2014

Last Updated

October 25, 2017

Sponsor

University College, London

1. Study Identification

Unique Protocol Identification Number

NCT02252328

Brief Title

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

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Unknown status

Study Start Date

September 2015 (undefined)

Primary Completion Date

August 2018 (Anticipated)

Study Completion Date

August 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University College, London

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Uveitis

Keywords

Uveitis, Simvastatin, Visual acuity, Corticosteroids, Immunosuppression

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Simvastatine

Arm Type

Experimental

Arm Description

Group of patients receiving simvastatin 80mg once daily in addition to standard care

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Group of patients receiving placebo once daily in addition to standard care

Intervention Type

Drug

Intervention Name(s)

Simvastatin

Intervention Description

Simvastatin 80mg once daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo tablets once daily

Primary Outcome Measure Information:

Title

1. Change in dose (mg) of prednisolone after 12 months of treatment

Description

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?

Time Frame

12 months

Secondary Outcome Measure Information:

Title

The mean reduction in prednisolone achieved at 24 months.

Time Frame

24 months

Title

The chnage in the number of 2nd-line immunosuppressive drugs at 24 months

Time Frame

24 months

Title

The number of disease relapses by 24 months

Time Frame

24 months

Title

Blood cholesterol and lipid levels at 24 months as compared to baseline

Time Frame

24 months

Title

Change in visual acuity at 12 and 24 months as compared to baseline

Time Frame

12 and 24 months

Title

Treg and Th17 levels at 12 and 24 months as compared to baseline

Time Frame

12 and 24 months

Title

Number of patients with adverse events.

Time Frame

24 months

Title

The change in dose (mg) of 2nd-line immunosuppressive drugs at 24months

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Oren Tomkins-Netzer, MD, PhD

Organizational Affiliation

University College, London

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Sue Lightman, PhD,FRCOphth

Organizational Affiliation

University College, London

Official's Role

Study Chair

Facility Information:

Facility Name

Moorfields Eye Hospital

City

London

ZIP/Postal Code

EC1V 2PD

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24655729

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.

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Use of Simvastatin as a Steroid Sparing Agent for Uveitis Patients

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