Clinical trial NCT01320345: The Fenofibrate And Microvascular Events in Type 1 Diabetes 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Diabetic Retinopathy
Diabetic Nephropathies
Keywords: Diabetes Mellitus
Type 1 Diabetes Mellitus
Retinopathy
Diabetic Nephropathy
Fenofibrate
Lead sponsor: University of Sydney
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Juvenile Diabetes Research Foundation Australia
name: Mylan Pharmaceuticals Inc
First posted: 2011-03-22
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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.

Primary outcomes:
measure: Occurrence of clinical significant retinopathy progression.
timeFrame: As reported throughout the study and/or annual eye assessment post-randomisation
Secondary outcomes:
measure: The individual components of the primary endpoint
timeFrame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
measure: Occurrence of clinically significant macula oedema (CSME).
timeFrame: As reported throughout the study
measure: Need for laser surgery for DR
timeFrame: As reported throughout the study
measure: Need for intraocular anti-VEGF or corticosteroid injection or vitrectomy
timeFrame: As reported throughout the study
measure: Visual acuity.
timeFrame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
measure: Macular volume and thickness
timeFrame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
measure: Albuminuria.
timeFrame: 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.
measure: Estimated glomerular filtration rate.
timeFrame: At study completion and washout visit
measure: Peripheral neuropathy status
timeFrame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
measure: Autonomic neuropathy.
timeFrame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
measure: Total cardiovascular events.
timeFrame: As reported throughout the study.
measure: Frequency of foot ulcer and non-traumatic amputation.
timeFrame: As reported throughout the study
Other outcomes:
measure: Lipid and lipoprotein levels
timeFrame: At baseline and end of study
measure: Biomarkers and molecular markers
timeFrame: At baseline and end of study
measure: Quality of Life questionnaire
timeFrame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Garvan Institute of Medical Research
state: New South Wales
city: Liverpool
country: Australia
facility: Retina Associates - South West Retina
state: New South Wales
city: Merewether
country: Australia
facility: Hunter Diabetes Centre
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Oaklands Park
country: Australia
facility: Southern Adelaide Diabetes and Endocrine Services
state: South Australia
city: Geelong
country: Australia
facility: University Hospital Geelong
state: Victoria
city: Heidelberg
country: Australia
facility: Heidelberg Repatriation Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Baker Heart and Diabetes Institute
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Hospital
state: Western Australia
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Auckland
country: New Zealand
facility: Auckland Diabetes Centre
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
Study officials:
affiliation: NHMRC Clinical Trials Centre, The University of Sydney
name: Anthony Keech, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: NHMRC Clinical Trials Centre, The University of Sydney
name: Alicia Jenkins, Professor
role: PRINCIPAL_INVESTIGATOR
References: