The Fenofibrate And Microvascular Events in Type 1 Diabetes Eye.

Type 1 Diabetes Mellitus Clinical Trial

— FAME 1 EYE  

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01320345
• Other study ID #: FAME0001
• Secondary ID: ACTRN12611000249
• Status: Recruiting
• Phase: Phase 3
• Start date: November 3, 2016
• Est. completion date: December 2025

Study information

• Verified date: December 2022
• Source: University of Sydney
• Contact: Liping Li
• Phone: +61 2 9562 5000
• Email: fame1eye.study[@]sydney.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetic Nephropathies
• Diabetic Retinopathy
• Kidney Diseases
• Retinal Diseases
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Fenofibrate
145 mg tablet of fenofibrate administered once daily for 36 months.
• Inert lactose placebo
Insert lactose tablet matching active tablet administered once daily for 36 months.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Cairns Hospital	Cairns	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Garvan Institute of Medical Research	Darlinghurst	New South Wales
Australia	Fremantly Hospital	Fremantle	Western Australia
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Barwon Health	Geelong	Victoria
Australia	Heidelberg Repatriation Hospital	Heidelberg	Victoria
Australia	Retina Associates - South West Retina	Liverpool	New South Wales
Australia	Baker Heart and Diabetes Institute	Melbourne	Victoria
Australia	St Vincent's Hospital Melbourne	Melbourne	Victoria
Australia	Hunter Diabetes Centre	Merewether	New South Wales
Australia	Southern Adelaide Diabetes and Endocrine Services	Oaklands Park	South Australia
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	Mater Adult Hospital	South Brisbane	Queensland
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Hong Kong	Prince of Wales Hospital	Shatin	New Territories
New Zealand	Auckland Diabetes Centre	Auckland
New Zealand	Christchurch Hospital	Christchurch

Sponsors (4)

Lead Sponsor	Collaborator
University of Sydney	Juvenile Diabetes Research Foundation Australia, Mylan Pharmaceuticals Inc, National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

Australia,  Hong Kong,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Lipid and lipoprotein levels	Lipid and lipoprotein levels	At baseline and end of study
Other	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
Other	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
Primary	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	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).
Secondary	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
Secondary	Need for laser surgery for DR	Need for laser surgery for DR	As reported throughout the study
Secondary	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
Secondary	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).
Secondary	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).
Secondary	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.
Secondary	Estimated glomerular filtration rate.	Estimated glomerular filtration rate using Modification of Diet in Renal Disease (MDRD) formula.	At study completion and washout visit
Secondary	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).
Secondary	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).
Secondary	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.
Secondary	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