Effects of Oral Fenofibrate on Retinal Thickness and Macular Volume

NCT ID: NCT04885153

Last Updated: 2021-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-01
• Study Completion Date: 2017-07-01

Brief Summary

Lipid levels in the blood are proposed to play a role in the progression of diabetic retinopathy. Lipid levels can be controlled with dyslipidemic drugs, such as fenofibrate. Fenofibrate is known to prevent diabetic microvascular complications by decreasing cholesterol and triglyceride levels. This study aims to investigate the effects of oral fenofibrate on central macular thickness (CMT) and macular volume, as well as on specific biomarkers of endothelial dysfunction (eNOS), inflammation (VCAM-1), and angiogenesis (VEGF) in DR individuals with dyslipidemia.

Detailed Description

This study was a prospective, double-blind, controlled clinical trial. The study was conducted from 2016 to 2017 at Vitreo-retina Clinic, Department of Ophthalmology, RSCM Kirana. The subjects were non-proliferative diabetic retinopathy (NPDR) patients with dyslipidemia or normal lipid profile with treatment. The outcome measures were central macular thickness (CMT), macular volume, endothelial nitric oxide (eNOS), vascular endothelial growth factor (VEGF), vascular cell adhesion molecule 1 (VCAM-1).

The operational definitions used in our study are as follows:

• Blood glucose control: glucose control status based on HbA1c levels within the last 3 month. Normal values < 7%.
• Dyslipidemia: patient is diagnosed with dyslipidemia if at least one out of four lipid profile parameters is above normal limits (LDL cholesterol ≥ 130, mg/dL, total cholesterol ≥ 200 mg/dL, HDL cholesterol < 40 mg/dL, triglyceride ≥ 150 mg/dL) or normal with treatment.
• Diabetic retinopathy: changes in retinal microvascular based on diabetic retinopathy classification
• Endothelial dysfunction: plasma endothelial nitric oxide (eNOS)
• Inflammation: plasma vascular endothelial growth factor (VEGF)
• Angiogenesis: plasma vascular cell adhesion molecule 1 (VCAM-1).
• Central macular thickness: thickness of fovea centralis based on OCT
• Macular volume: the volume of the retina in the central 6 mm of the macula

Subjects with severe renal failure, allergy towards fenofibrate, pregnant women, and subjects who have undergone laser photocoagulation treatment or intravitreal injection in last 6 months, were excluded. Subjects who did not take medication > 20% of scheduled drug doses were dropped out.

Subjects were allocated into two groups with block randomizations. Sample size calculation revealed a minimum sample size of 18 eyes. Subjects in intervention group received 18 mg of simvastatin and 200 mg of fenofibrate once daily for three months, and subjects in control group received 18 mg of simvastatin and placebo.

All subjects underwent eye examination, fundus photo, and macular spectral-domain optical coherence tomography (SD-OCT), as well as monthly blood and urine laboratory tests. All of the subjects were examined for their uncorrected visual acuity with Snellen chart, intraocular pressure, slitlamp biomicroscopy, and funduscopy through condensed 78 D lens. Fundus photo of both eyes of the subjects were taken before intervention, on every monthly follow-up during intervention, and at the end of study. Fundus photo was done using fundus digital camera (Kowa Medical Equipments, Japan). All fundus photos were read by two vitreo-retina consultants as independent readers. Evaluation of DR degree and the presence of diabetic macula edema (DME) was based on standard of ETDRS severity scale. Inter-reader reliability was also analyzed using Kappa coefficient calculation, which was considered to be acceptable if the value was more than 0.6.

Laboratory tests including HbA1c, triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, and specific eNOS, VEGF, and serum VCAM-1 biologic markers, were examined at baseline prior to drug administration, and at the end of the study after 3 months. In addition, at the beginning of the study, first, second and third month controls were examined for microalbuminuria, SGOT, SGPT, urine creatinine, blood urea, blood creatinine, and eGFR, to monitor the safety of drug delivery.

Data processing was done using IBM Statistic Program for Social Science (SPSS) version 20. All outcomes were numerical variables, comparison of numerical data between the two groups was performed with unpaired t-test if normal data distribution was fulfilled, otherwise non-parametric Mann Whitney test was used if the data was not normally distributed. To assess the difference between two paired data, Wilcoxon test was used.

Conditions

Diabetic Retinopathy; Dyslipidemias; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention Group

Subjects who were given simvastatin 10 mg and fenofibrate 200 mg.

Group Type: EXPERIMENTAL

Fenofibrate

Intervention Type: DRUG

Patients were given simvastatin 10 mg and fenofibrate 200 mg daily for three months and were evaluated monthly.

Control Group

Subjects who were given simvastatin 10 mg and placebo (lactic acid) 200 mg.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients were given simvastatin 10 mg and placebo (lactic acid) 200 mg daily for three months and were evaluated monthly.

Interventions

Fenofibrate

Patients were given simvastatin 10 mg and fenofibrate 200 mg daily for three months and were evaluated monthly.

Intervention Type: DRUG

Placebo

Patients were given simvastatin 10 mg and placebo (lactic acid) 200 mg daily for three months and were evaluated monthly.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults with type 2 DM
• Confirmed DR (with bio-microscopy examination and fundus photos of both eyes)
• Dyslipidemia or normal lipid profile with treatment
• Sign informed consent

Exclusion Criteria

• Subjects with severe renal failure
• Subjects with allergy towards fenofibrate
• Pregnant women
• Subjects who have undergone laser photocoagulation treatment or intravitreal injection in last 6 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indonesia University

OTHER

Sponsor Role: lead

Responsible Party

Gitalisa Andayani

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gitalisa Andayani, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Ophthalmology, Cipto Mangunkusumo Hospital

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Other Identifiers

FenofibrateRetinaGitalisa

Identifier Type: -

Identifier Source: org_study_id