Simvastatin in Uveitis

Open-label Randomized Study of Efficacy and Safety of Simvastatin in Uveitis

The study evaluates anti-inflammatory effects and safety of simvastatin in non-infectious uveitis.

Study Overview

• Status: Completed
• Conditions: Uveitis
• Intervention / Treatment: Drug: Simvastatin 40mg

Detailed Description

3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce local and systemic inflammation in animal models of various autoimmune disorders including uveitis. In this open-label, randomized study clinical efficacy and tolerability of simvastatin 40 mg/day for 8 weeks is evaluated.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630047
    • Laboratory of Clinical Immunopharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- diagnosis of active non-infectious uveitis

Exclusion Criteria:

• serious liver or kidney disease
• increased transaminase levels of >1.5 ULN
• planned or active pregnancy
• use of fibrates, nicotinic acid, cyclosporine A, antifungal drugs, macrolide antibiotics, verapamil, and grapefruit juice (>1 L/day).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin and standard treatment; 40 mg simvastatin per day for 2 months in addition to conventional treatment of uveitis	Drug: Simvastatin 40mg; Other Names: simvastatin
No Intervention: standard treatment; conventional treatment of uveitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of corticosteroid sparing control of ocular inflammation	Incident cases of corticosteroid sparing control of ocular inflammation will be defined using following criteria: ≤0.5+ anterior chamber cells, ≤0.5+ vitreous haze, and no active retinal/choroidal lesions; and; ≤10 mg of oral prednisone daily and ≤2 drops of prednisolone acetate 1% (or equivalent) a day; The patient should fullfill both criteria to be classified as having corticosteroid sparing control of ocular inflammation	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual acuity	Assessment of visual acuity using the Golovin-Sivtsev table	Baseline, 4 weeks, 8 weeks
Anterior chamber cells	The grades for anterior chamber cells were 0 (<1 cell), 0.5 (1-5 cells), 1 (6-15 cells), 2 (16-25 cells), 3 (26-50 cells), or 4 (>50 cells)	Baseline, 4 weeks, 8 weeks
Anterior chamber flare	The grades are the following: 0 (none), 1+ (faint), 2+ (moderate (iris and lens details clear)), 3+ (marked (iris and lens details hazy)), 4+ (intense (fibrin or plastic aqueous)	Baseline, 4 weeks, 8 weeks
Vitreous haze	Nussenblatt scale: 0 (no flare), 0.5+ (trace), 1+ (clear optic disc and vessels, hazy nerve fiber layer), 2+ (hazy optic disc and vessels), 3+ (optic disc visible), 4+ (optic disc not visible)	Baseline, 4 weeks, 8 weeks
Intraocular pressure	Measured using Maklakov tonometer	Baseline, 4 weeks, 8 weeks
Changes in tear IL-6	Concentrations of IL-6 (pg/ml) in tear samples	Baseline, 8 weeks
Changes in tear IL-8	Concentrations of IL-8 (pg/ml) in tear samples	Baseline, 8 weeks
Changes in tear IL-10	Concentrations of IL-10 (pg/ml) in tear samples	Baseline, 8 weeks
Changes in tear TNFα	Concentrations of TNFα (pg/ml) in tear samples	Baseline, 8 weeks
Changes in tear IFN-γ	Concentrations of IFN-γ (pg/ml) in tear samples	Baseline, 8 weeks
Incidence of corticosteroid sparing control of ocular inflammation	Incident cases of corticosteroid sparing control of ocular inflammation will be defined using following criteria: ≤0.5+ anterior chamber cells, ≤0.5+ vitreous haze, and no active retinal/choroidal lesions; and; ≤10 mg of oral prednisone daily and ≤2 drops of prednisolone acetate 1% (or equivalent) a day; The patient should fullfill both criteria to be classified as having corticosteroid sparing control of ocular inflammation	4 weeks

Collaborators and Investigators

• Sponsor: Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology

Publications and helpful links

General Publications

• Shirinsky IV, Biryukova AA, Kalinovskaya NY, Shirinsky VS. Tear cytokines as potential biomarkers in non-infectious uveitis: post hoc analysis of a randomised clinical trial. Graefes Arch Clin Exp Ophthalmol. 2020 Aug;258(8):1813-1819. doi: 10.1007/s00417-020-04707-7. Epub 2020 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: November 28, 2019
• First Posted (Actual): December 3, 2019

Study Record Updates

• Last Update Posted (Actual): December 3, 2019
• Last Update Submitted That Met QC Criteria: November 28, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: SMV003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No