Effects of Oral Fenofibrate on Retinal Thickness and Macular Volume

NCT04885153 | Completed

• 1 other identifier: FenofibrateRetinaGitalisa
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Diabetic Retinopathy; Dyslipidemias; Diabetes Mellitus

Keywords

diabetes mellitus; diabetic retinopathy; dyslipidemia; fenofibrate

Outcome Measures

Primary Outcomes (5)

• Changes from Baseline Central Macular Thickness (CMT) at 3 Months

  Thickness of fovea centralis based on OCT

  Evaluated at baseline and monthly for three months

• Changes from Baseline Macular Volume at 3 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

  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

  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

  Protein that functions for cell adhesion

  Evaluated at baseline and after three months (by the end of the study)

Study Arms (2)

Intervention Group

EXPERIMENTAL

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

Drug: Fenofibrate

Control Group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Fenofibrate DRUG

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

Intervention Group

Placebo DRUG

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

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indonesia University: lead

Related Publications (12)

• Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012 Mar;35(3):556-64. doi: 10.2337/dc11-1909. Epub 2012 Feb 1.

  PMID: 22301125 BACKGROUND

• Landmesser U, Hornig B, Drexler H. Endothelial dysfunction in hypercholesterolemia: mechanisms, pathophysiological importance, and therapeutic interventions. Semin Thromb Hemost. 2000;26(5):529-37. doi: 10.1055/s-2000-13209.

  PMID: 11129409 BACKGROUND

• Xu J, Zou MH. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation. 2009 Sep 29;120(13):1266-86. doi: 10.1161/CIRCULATIONAHA.108.835223. No abstract available.

  PMID: 19786641 BACKGROUND

• Koshy J, Koshy JM, Thomas S, Kaur G, Mathew T. Should we start all patients with diabetic retinopathy on fenofibrates? Middle East Afr J Ophthalmol. 2013 Oct-Dec;20(4):309-14. doi: 10.4103/0974-9233.120012.

  PMID: 24339680 BACKGROUND

• Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse D, Williamson E, Merrifield A, Laatikainen LT, d'Emden MC, Crimet DC, O'Connell RL, Colman PG; FIELD study investigators. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007 Nov 17;370(9600):1687-97. doi: 10.1016/S0140-6736(07)61607-9. Epub 2007 Nov 7.

  PMID: 17988728 BACKGROUND

• Noonan JE, Jenkins AJ, Ma JX, Keech AC, Wang JJ, Lamoureux EL. An update on the molecular actions of fenofibrate and its clinical effects on diabetic retinopathy and other microvascular end points in patients with diabetes. Diabetes. 2013 Dec;62(12):3968-75. doi: 10.2337/db13-0800.

  PMID: 24264394 BACKGROUND

• Wright AD, Dodson PM. Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Eye (Lond). 2011 Jul;25(7):843-9. doi: 10.1038/eye.2011.62. Epub 2011 Mar 25.

  PMID: 21436845 BACKGROUND

• Massin P, Peto T, Ansquer JC, Aubonnet P, MacuFEN Study Investigators FT. Effects of fenofibric acid on diabetic macular edema: the MacuFen study. Ophthalmic Epidemiol. 2014 Oct;21(5):307-17. doi: 10.3109/09286586.2014.949783. Epub 2014 Aug 18.

  PMID: 25133794 BACKGROUND

• Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d. doi: 10.1093/eurheartj/ehr304. Epub 2011 Sep 1.

  PMID: 21890489 BACKGROUND

• Gustavsson C, Agardh CD, Zetterqvist AV, Nilsson J, Agardh E, Gomez MF. Vascular cellular adhesion molecule-1 (VCAM-1) expression in mice retinal vessels is affected by both hyperglycemia and hyperlipidemia. PLoS One. 2010 Sep 13;5(9):e12699. doi: 10.1371/journal.pone.0012699.

  PMID: 20856927 BACKGROUND

• Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004 Dec;56(4):549-80. doi: 10.1124/pr.56.4.3.

  PMID: 15602010 BACKGROUND

• Saxena S, Khatri M, Nadri G, Ankita. Pathogenic Mechanisms for Outer Retinal Layer Changes in Diabetic Retinopathy. Ann Diabetes Metab Disord Contr. 2017; 1:113.

  BACKGROUND

MeSH Terms

Conditions

Diabetic Retinopathy; Dyslipidemias; Diabetes Mellitus

Interventions

Fenofibrate

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Endocrine System Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Glucose Metabolism Disorders

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones

Study Officials

• Gitalisa Andayani, MD, PhD

  Department of Ophthalmology, Cipto Mangunkusumo Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

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

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: May 13, 2021
• Study Start: November 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: May 13, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share