Effects of Oral Fenofibrate on Retinal Thickness and Macular Volume

May 9, 2021 updated by: Gitalisa Andayani, Indonesia University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

36

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indonesia University

Investigators

  • Principal Investigator: Gitalisa Andayani, MD, PhD, Department of Ophthalmology, Cipto Mangunkusumo Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2016

Primary Completion (Actual)

July 1, 2017

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

January 21, 2021

First Submitted That Met QC Criteria

May 9, 2021

First Posted (Actual)

May 13, 2021

Study Record Updates

Last Update Posted (Actual)

May 13, 2021

Last Update Submitted That Met QC Criteria

May 9, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FenofibrateRetinaGitalisa

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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