ActivePhase 3ACTRN12611000249954

The Fenofibrate And Microvascular Events in Type 1 diabetes Eye: A randomised trial to evaluate the efficacy on retinopathy and safety of fenofibrate in adults with type 1 diabete. A multicentre double-blind placebo-controlled study in Australia and internationally

Sponsor

NHMRC Clinical Trials Centre, University of Sydney

Enrollment

450 participants

Start Date

Nov 3, 2016

Study Type

Interventional

Conditions

Eye disease (retinopathy) in type 1 diabetes mellitus Diabetic nephropathy in type 1 diabetes mellitus

Summary

Diabetes is the commonest cause of adult onset blindness. Vision loss, which is irreversible, is a most feared complication of diabetes. A blood fat lowering drug called fenofibrate, available in Australia, 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 fenofibrate in 450 adults with Type 1 diabetes who are at high risk of eye damage.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria13

Eligibility criteria for the main study:
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-GAD, anti-A2, anti-ZnT8).
Age 18 years or over;
eGFR must exceed 30 ml/min/1.73m2;
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.;
All types of insulin therapy, with no restriction by level of HbA1c;
Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances;
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 Criteria19

Definite indication for or contraindications to fibrate treatment (Other lipid drugs [e.g. statins, ezetimibe, fish oils] are allowed.);
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);
Prior bilateral pan-retinal photocoagulation (PRP) treatment for diabetic retinopathy;
Prior bilateral intra-ocular injection(s) within the last 6 months;
Bilateral cataract surgery within the last 6 months;
Planned bilateral cataract surgery within the next 12 months;
History of any other non-diabetic eye disease that is or is likely to affect bilateral vision;
History of photosensitive skin rash or myositis;
Abnormal thyroid function (untreated);
Liver function tests exceeding 3xULN;
Persistent elevated unexplained blood CPK level above normal range;
Documented fasting TG levels >6.5 mmol/L;
History of pancreatitis, DVT or pulmonary embolism;
Use of investigational drugs in the prior 8 weeks;
Any unstable condition in last 3 months including active sepsis, diabetic ketoacidosis;
MI, unstable angina, stroke or heart failure within last 6 months;
Diagnosed cancer with ongoing treatment or prognosis anticipated at <5 years;
Any obstacle to regular follow-up including scheduled clinic attendances;
Prior or planned organ transplantation (including islet cells) with subsequent continued immunosuppression therapy.

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Interventions

All eligible participants will complete a 6 week run-in phase comprising either a once daily tablet of 145 mg fenofibrate or matching (inert lactose) placebo. After completion of the run-in period participants will be immediately randomised to either a once daily tablet of 145 mg fenofibrate or placebo, taken for 36 months. Participants ineligible for the run-in phase will be followed up by an annual phone call and a clinic visit at the end of the follow up period for blood and urine sampling. Concurrent to the main study a small number of age and gender matched nondiabetic reference group participants will provide blood and urine samples for comparison research at a screening visit and at the conclusion of the trial (approximately 36 months after their screening visit). Compliance and safety will be monitored by clinic visits.