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

University of Sydney

Status and phase: Enrolling; Phase 3

Conditions: Diabetic Nephropathies; Type 1 Diabetes Mellitus; Diabetic Retinopathy

Treatments: Drug: Inert lactose placebo; Drug: Fenofibrate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01320345

FAME0001

ACTRN12611000249954 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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450 participants in 2 patient groups, including a placebo group

Fenofibrate

Experimental group

Description:

145 mg tablet of fenofibrate administered daily for 36 months.

Treatment:

Drug: Fenofibrate

Placebo

Placebo Comparator group

Description:

Inert lactose tablet (otherwise matching active) administered daily for 36 months.

Treatment:

Drug: Inert lactose placebo