Effects of Oral Fenofibrate on Retinal Thickness and Macular Volume

Sponsor

Indonesia University (Other)

Overall Status

Completed

CT.gov ID

NCT04885153

Collaborator

(none)

Enrollment

Arms

Actual Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Retinopathy Dyslipidemias Diabetes Mellitus	Drug: Fenofibrate Drug: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients were divided into two groups, which were intervention group (simvastatin+fenofibrate) and control group (simvastatin+placebo).Patients were divided into two groups, which were intervention group (simvastatin+fenofibrate) and control group (simvastatin+placebo).

Masking:

Single (Care Provider)

Masking Description:

200 mg of micronized fenofibrate and placebo (lactic acid) were repackaged into identical capsules and then put inside identical plastic pot by the Pharmacy Unit of Cipto Mangunkusumo Hospital.

Primary Purpose:

Treatment

Official Title:

Effects of Oral Fenofibrate on Retinal Thickness and Macular Volume: Assessments on Retinal Endothelial Vascular Dysfunction, Inflammation, and Angiogenesis in Diabetic Retinopathy With Dyslipidemia

Actual Study Start Date :

Nov 1, 2016

Actual Primary Completion Date :

Jul 1, 2017

Actual Study Completion Date :

Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Group Subjects who were given simvastatin 10 mg and fenofibrate 200 mg.	Drug: Fenofibrate Patients were given simvastatin 10 mg and fenofibrate 200 mg daily for three months and were evaluated monthly.
Placebo Comparator: Control Group Subjects who were given simvastatin 10 mg and placebo (lactic acid) 200 mg.	Drug: Placebo Patients were given simvastatin 10 mg and placebo (lactic acid) 200 mg daily for three months and were evaluated monthly.

Arm

Intervention/Treatment

Experimental: Intervention Group

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

Drug: Fenofibrate

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

Placebo Comparator: Control Group

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

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

Changes from Baseline Central Macular Thickness (CMT) at 3 Months [Evaluated at baseline and monthly for three months]
Thickness of fovea centralis based on OCT
Changes from Baseline Macular Volume at 3 Months [Evaluated at baseline and monthly for three months]
Volume of the retina in the central 6 mm of the macula based on OCT
Changes from Baseline Endothelial Nitric Oxide Synthase (eNOS) at 3 Months [Evaluated at baseline and after three months (by the end of the study)]
Enzyme that produces protective molecule of the blood vessels
Changes from Baseline Vascular Endothelial Growth Factor (VEGF) at 3 Months [Evaluated at baseline and after three months (by the end of the study)]
Signaling protein that promotes angiogenesis
Changes from Baseline Vascular Cell Adhesion Molecule-1 (VCAM -1) at 3 Months [Evaluated at baseline and after three months (by the end of the study)]
Protein that functions for cell adhesion

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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