The Fenofibrate And Microvascular Events in Type 1 Diabetes Eye. (FAME 1 EYE)

A Randomised Trial to Evaluate the Efficacy on Retinopathy and Safety of Fenofibrate in Adults With Type 1 Diabetes. A Multicentre Double-blind Placebo-controlled Study in Australia and Internationally.

The purpose of this study is to evaluate the potential benefits of 145 mg of daily fenofibrate in adults with type 1 diabetes mellitus and pre-existing non-proliferative diabetic retinopathy.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Retinopathy; Diabetic Nephropathies; Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Fenofibrate; Drug: Inert lactose placebo

Detailed Description

Diabetes is the most common cause of adult onset blindness. Irreversible vision loss is a most feared complication of diabetes. Fenofibrate is a blood fat lowering drug available in Australia and has been shown to reduce eye damage in people with Type 2 diabetes by 35-40%, and to prevent eye damage in Type 1 diabetic animal models. This study will evaluate the potential benefits of oral Fenofibrate 145mg once daily for average 36 months in 450 adults with Type 1 diabetes mellitus who are at high risk of eye damage.

• Study Type: Interventional
• Enrollment (Actual): 412
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • Garvan Institute of Medical Research
    • Liverpool, New South Wales, Australia, 2170
      • Retina Associates - South West Retina
    • Merewether, New South Wales, Australia, 2291
      • Hunter Diabetes Centre
    • Randwick, New South Wales, Australia, 2032
      • Prince of Wales Hospital
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Cairns Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Adult Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Oaklands Park, South Australia, Australia, 5046
      • Southern Adelaide Diabetes and Endocrine Services
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • University Hospital Geelong
    • Heidelberg, Victoria, Australia, 3081
      • Heidelberg Repatriation Hospital
    • Melbourne, Victoria, Australia, 3004
      • Baker Heart and Diabetes Institute
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Fremantle Hospital
• Hong Kong
  • New Territories
    • Shatin, New Territories, Hong Kong
      • Prince of Wales Hospital
• New Zealand
  • Auckland, New Zealand, 1051
    • Auckland Diabetes Centre
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
• United Kingdom
  • Belfast, United Kingdom, BT12 6BA
    • Belfast Health and Social Care Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria (for the main study):

1. Men or non-pregnant women (on acceptable contraception) with T1D* according to standard criteria:

   • T1D defined as either (1) T1D diagnosed below 40 years of age and insulin therapy commencing within one year of T1D diagnosis, or (2) T1D diagnosed before, at or after 40 years of age along with: i) Documented history of ketoacidosis, and/or ii) Documented history of very low or undetectable C-peptide (fasting <200 nmol/L or 0.2 pmol/L), and/or iii) Documented history of T1D related autoantibody/ies (anti-Glutamic acid decarboxylase, anti-A2, anti-ZnT8).
2. Age 18 years or over;
3. Estimated glomerular filtration rate (eGFR) must exceed 30 ml/min/1.73m2;
4. Must have at least one eligible eye with non-proliferative retinopathy (ETDRS score 35-53 inclusive) confirmed by current retinal photography within the last 3 months (irrespective of prior laser therapy). Note: Any eye having undergone prior pan-retinal laser therapy is not eligible, but prior focal, macular or grid laser does not exclude that eye from eligibility.;
5. All types of insulin therapy, with no restriction by level of HbA1c;
6. Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances;
7. Able to personally read and understand the Participant Information and Consent Form and provide written, signed and dated informed consent to participate in the study.

Eligibility criteria for the reference group is limited to age and gender matched individuals who do not have T1D.

Exclusion criteria:

1. Definite indication for or contraindications to fibrate treatment (Other lipid drugs [e.g. statins, ezetimibe, fish oils] are allowed.);
2. Need for bilateral intra-ocular treatment or laser photocoagulation therapy within the next 3 months (this exclusion only applies to retinal laser photocoagulation treatment to the posterior pole i.e. laser correction of corneas for short-sightedness is NOT an exclusion criterion);
3. Prior bilateral pan-retinal photocoagulation (PRP) treatment for diabetic retinopathy;
4. Prior bilateral intra-ocular injection(s) within the last 6 months;
5. Bilateral cataract surgery within the last 6 months;
6. Planned bilateral cataract surgery within the next 12 months;
7. History of any other non-diabetic eye disease that is or is likely to affect bilateral vision;
8. History of photosensitive skin rash or myositis;
9. Abnormal thyroid function (untreated);
10. Liver function tests exceeding 3x upper limit of normal (ULN);
11. Persistent elevated unexplained blood creatinine phosphokinase level above normal range;
12. Documented fasting triglycerides (TG) levels >6.5 mmol/L;
13. History of pancreatitis, deep vein thrombosis (DVT) or pulmonary embolism;
14. Use of investigational drugs in the prior 8 weeks;
15. Any unstable condition in last 3 months including active sepsis, diabetic ketoacidosis;
16. Myocardial infarction (MI), unstable angina, stroke or heart failure within last 6 months;
17. Diagnosed cancer with ongoing treatment or prognosis anticipated at <5 years;
18. Any obstacle to regular follow-up including scheduled clinic attendances;
19. Prior or planned organ transplantation (including islet cells) with subsequent continued immunosuppression therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fenofibrate; 145 mg tablet of fenofibrate administered daily for 36 months.	Drug: Fenofibrate; 145 mg tablet of fenofibrate administered once daily for 36 months.
Placebo Comparator: Placebo; Inert lactose tablet (otherwise matching active) administered daily for 36 months.	Drug: Inert lactose placebo; Insert lactose tablet matching active tablet administered once daily for 36 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of clinical significant retinopathy progression.	Comprising 2-step progression of ETDRS score (to at least moderately severe grade), clinically significant macular oedema, need for laser surgery, need for intraocular anti-VEGF or corticosteroid therapy or vitrectomy, adjudicated to be for diabetic retinopathy (DR)	As reported throughout the study and/or annual eye assessment post-randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The individual components of the primary endpoint	Clinically significant retinopathy progression, 2-step progression of ETDRS score	At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Occurrence of clinically significant macula oedema (CSME).	Occurrence of clinically significant macula oedema (CSME) per standard ophthalmological assessment or laser therapy.	As reported throughout the study
Need for laser surgery for DR	Need for laser surgery for DR	As reported throughout the study
Need for intraocular anti-VEGF or corticosteroid injection or vitrectomy	Need for intraocular anti-VEGF or corticosteroid injection or vitrectomy for DR	As reported throughout the study
Visual acuity.	Visual acuity using ETDRS/LogMar or Snellen Chart	At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Macular volume and thickness	Macular volume and thickness by Optical Coherence Tomography (OCT)	At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Albuminuria.	Albuminuria measured as urinary albumin:creatinine ratio.	At baseline, 12 m post-randomisation, 24 m post-randomisation, the end of study visit (which is on average 36 months post-randomisation) and wash-out visit.
Estimated glomerular filtration rate.	Estimated glomerular filtration rate using Modification of Diet in Renal Disease (MDRD) formula.	At study completion and washout visit
Peripheral neuropathy status	Peripheral neuropathy status assessed by temperature & vibration sensation and monofilament test.	At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Autonomic neuropathy.	Autonomic neuropathy (QTc and R-R intervals) on annual ECGs.	At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Total cardiovascular events.	Total cardiovascular events including myocardial infarction, stroke, sudden cardiac death, hospitalisation for acute coronary syndrome or any revascularisation events.	As reported throughout the study.
Frequency of foot ulcer and non-traumatic amputation.	Foot ulcer and/or non-traumatic amputation are reported by site during the study.	As reported throughout the study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid and lipoprotein levels	Lipid and lipoprotein levels	At baseline and end of study
Biomarkers and molecular markers	Markers of inflammation, glycation and oxidative stress, angiogenesis and adipocyte function, and molecular markers, as change from baseline with study treatment	At baseline and end of study
Quality of Life questionnaire	Quality of Life questionnaire completed by participants annually	At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit

Collaborators and Investigators

• Sponsor: University of Sydney
• Collaborators: National Health and Medical Research Council, Australia; Mylan Pharmaceuticals Inc; Juvenile Diabetes Research Foundation Australia
• Investigators: Principal Investigator: Anthony Keech, Professor, NHMRC Clinical Trials Centre, The University of Sydney; Principal Investigator: Alicia Jenkins, Professor, NHMRC Clinical Trials Centre, The University of Sydney

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2016
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 18, 2011
• First Submitted That Met QC Criteria: March 21, 2011
• First Posted (Estimated): March 22, 2011

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Type 1 Diabetes Mellitus; Fenofibrate; Retinopathy; Diabetic Nephropathy
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Eye Diseases; Diabetic Angiopathies; Diabetes Complications; Nutritional and Metabolic Diseases; Retinal Diseases; Diabetic Retinopathy; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Organic Chemicals; Ethers; Hydrocarbons; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Butyrates; Phenyl Ethers; Ketones; Fibric Acids; Isobutyrates; Benzophenones; Fenofibrate
• Other Study ID Numbers: FAME0001; ACTRN12611000249954 (Registry Identifier: Australian New Zealand Clinical Trials Registry (ANZCTR))

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