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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indonesia University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 21, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 13, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 13, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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Conditions

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