Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12611000249954
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
7/03/2011
Date registered
Help: Date registered
7/03/2011
Date last updated
Help: Date last updated
6/12/2025
Date data sharing statement initially provided
Help: Data sharing statement date
10/07/2019
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
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
Scientific title
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
Additional trial identifiers [1] 259745 0
N/A
Universal Trial Number (UTN)
Trial acronym
FAME1 Eye
Related trial records

Health condition
Health condition(s) studied:
Eye disease (retinopathy) in type 1 diabetes mellitus 261330 0
Diabetic nephropathy in type 1 diabetes mellitus 261331 0
Condition category
Condition code
Eye 259475 259475 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 259476 259476 0 0
Diabetes
Renal and Urogenital 259477 259477 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
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.
Intervention code [1] 264177 0
Treatment: Drugs
Description of the comparator or control
Participants randomised to the placebo arm will take a matched, once daily inert lactose tablet for 36 months.
Control group
Placebo

Outcomes
Primary outcome [1] 262287 0
Occurrence of clinical significant retinopathy progression: this is a composite outcome of 2-step progression of ETDRS score (using retinal photography to at least moderately severe grade), or clinically significant macular oedema, or need for laser surgery, or need for intraocular anti-VEGF or corticosteroid therapy or vitrectomy, (reported by site investigator) adjudicated to be for diabetic retinopathy (DR)
Timepoint [1] 262287 0
As reported throughout the study and/or annual eye assessment with retinal photography completed 12 monthly for average of 3 years post-randomisation
Secondary outcome [1] 273462 0
Albuminuria measured as urinary albumin:creatinine ratio.
Timepoint [1] 273462 0
At baseline, date of randomisation, 3 m post-randomisation, 12 m post-randomisation, 24 m post randomisation, end of study visit and wash-out visit.
Secondary outcome [2] 273463 0
Visual acuity using Snellen Chart
Timepoint [2] 273463 0
At baseline, 12 m post-randomisation, 24 m post randomisation and the end of study visit.
Secondary outcome [3] 273464 0
Corneal confocal microscopic measurement of neural damage (only assessed in a representative subset of the participants at sites with the specialised confocal microscope).
Timepoint [3] 273464 0
At baseline, 12 m post-randomisation, 24 m post randomisation and the end of study visit.
Secondary outcome [4] 273465 0
Estimated glomerular filtration rate using MDRD formula
Timepoint [4] 273465 0
At baseline, 12 m post-randomisation, 24 m post randomisation and the end of study visit.
Secondary outcome [5] 273466 0
Peripheral neuropathy status assessed by temperature sensation and monofilament sensation.
Timepoint [5] 273466 0
At baseline, 12 m post-randomisation, 24 m post randomisation and the end of study visit.
Secondary outcome [6] 273468 0
Blood lipids and biomarkers in plasma
Timepoint [6] 273468 0
At baseline, 12 m post-randomisation, 24 m post randomisation, end of study visit and wash-out visit.
Secondary outcome [7] 372449 0
Total cardiovascular events including myocardial infarction, stroke, sudden cardiac death, hospitalisation for acute coronary syndrome or any revascularisation events. These events are reported during the study by site to the sponsor.
Timepoint [7] 372449 0
As reported throughout the study.
Secondary outcome [8] 372450 0
Frequency of foot ulcer and non-traumatic amputation. These events are reported during the study by site to the sponsor.
Timepoint [8] 372450 0
As reported throughout the study
Secondary outcome [9] 372451 0
Macular volume measured by Optical Coherence Tomography (OCT).
Timepoint [9] 372451 0
On study completion.
Secondary outcome [10] 372452 0
Autonomic neuropathy (QTc and RR intervals) on annual ECGs.
Timepoint [10] 372452 0
At baseline, 12 m post-randomisation, 24 m post randomisation and the end of study visit.
Secondary outcome [11] 372453 0
Occurrence of clinically significant macula oedema (CSME) measured by optical coherence tomography and retinal photography.
Timepoint [11] 372453 0
At baseline, 12 m post-randomisation, 24 m post randomisation and the end of study visit.
Secondary outcome [12] 372454 0
Need for laser surgery for retinopathy reported during the study by site to the sponsor
Timepoint [12] 372454 0
As reported throughout the study
Secondary outcome [13] 372455 0
Need for intraocular anti-VEGF injection for retinopathy reported during the study by site to the sponsor
Timepoint [13] 372455 0
As reported throughout the study
Secondary outcome [14] 372456 0
Need for intraocular corticosteroid therapy for retinopathy reported during the study by site to the sponsor
Timepoint [14] 372456 0
As reported throughout the study
Secondary outcome [15] 372457 0
Need for vitrectomy for retinopathy reported during the study by site to the sponsor
Timepoint [15] 372457 0
As reported throughout the study
Secondary outcome [16] 372458 0
Macular thickness measured by Optical Coherence Tomography (OCT).
Timepoint [16] 372458 0
At baseline, 12 m post-randomisation, 24 m post randomisation and the end of study visit.

Eligibility
Key inclusion criteria
Eligibility 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-GAD, anti-A2, anti-ZnT8).

2) Age 18 years or over;
3) 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
Yes
Key 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 3xULN;
11) Persistent elevated unexplained blood CPK level above normal range;
12) Documented fasting TG levels >6.5 mmol/L;
13) History of pancreatitis, 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) 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by Flexetrials computer software.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic balanced randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/09/2011
Actual
3/11/2016
Date of last participant enrolment
Anticipated
30/06/2025
Actual
29/08/2025
Date of last data collection
Anticipated
4/12/2026
Actual
Sample size
Target
450
Accrual to date
Final
412
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 14181 0
Hunter Diabetes Centre - Merewether
Recruitment hospital [2] 14182 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 14183 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 14184 0
Concord Repatriation Hospital - Concord
Recruitment hospital [5] 14185 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [6] 14186 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [7] 14187 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment hospital [8] 14188 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment hospital [9] 14189 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [10] 14190 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [11] 14192 0
Fremantle Hospital and Health Service - Fremantle
Recruitment hospital [12] 14193 0
Prince of Wales Hospital - Randwick
Recruitment hospital [13] 21147 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [14] 21148 0
The Canberra Hospital - Garran
Recruitment hospital [15] 21149 0
Cairns Base Hospital - Cairns
Recruitment hospital [16] 21150 0
Garvan Institute of Medical Research - Darlinghurst
Recruitment hospital [17] 21151 0
Southern Adelaide Diabetes and Endocrine Services - Oaklands Park
Recruitment hospital [18] 21152 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [19] 21153 0
Sunshine Hospital - St Albans
Recruitment hospital [20] 21154 0
South West Retina Liverpool - Liverpool
Recruitment postcode(s) [1] 27160 0
2170 - Liverpool
Recruitment postcode(s) [2] 27161 0
2291 - Merewether
Recruitment postcode(s) [3] 27162 0
2050 - Camperdown
Recruitment postcode(s) [4] 27163 0
2065 - St Leonards
Recruitment postcode(s) [5] 27164 0
2139 - Concord
Recruitment postcode(s) [6] 27165 0
3065 - Fitzroy
Recruitment postcode(s) [7] 27166 0
3220 - Geelong
Recruitment postcode(s) [8] 27167 0
3081 - Heidelberg West
Recruitment postcode(s) [9] 27168 0
3004 - Melbourne
Recruitment postcode(s) [10] 27169 0
4102 - Woolloongabba
Recruitment postcode(s) [11] 27170 0
5000 - Adelaide
Recruitment postcode(s) [12] 27171 0
6160 - Fremantle
Recruitment postcode(s) [13] 27172 0
2031 - Randwick
Recruitment postcode(s) [14] 27173 0
5046 - Oaklands Park
Recruitment postcode(s) [15] 36007 0
3050 - Parkville
Recruitment postcode(s) [16] 36008 0
2605 - Garran
Recruitment postcode(s) [17] 36009 0
4870 - Cairns
Recruitment postcode(s) [18] 36010 0
2170 - Liverpool South
Recruitment postcode(s) [19] 36011 0
2010 - Darlinghurst
Recruitment postcode(s) [20] 36012 0
4101 - South Brisbane
Recruitment postcode(s) [21] 36013 0
3021 - St Albans
Recruitment outside Australia
Country [1] 21678 0
New Zealand
State/province [1] 21678 0
Christchurch, Auckland
Country [2] 24345 0
Hong Kong
State/province [2] 24345 0
Shatin, New Territories
Country [3] 26082 0
United Kingdom
State/province [3] 26082 0
Belfast

Funding & Sponsors
Funding source category [1] 264624 0
Commercial sector/Industry
Name [1] 264624 0
Mylan EPD Europe
Country [1] 264624 0
Switzerland
Funding source category [2] 264625 0
Government body
Name [2] 264625 0
National Health and Medical Research Council
Country [2] 264625 0
Australia
Funding source category [3] 303254 0
Other Collaborative groups
Name [3] 303254 0
JDRF (Australia)
Country [3] 303254 0
Australia
Primary sponsor type
University
Name
NHMRC Clinical Trials Centre, University of Sydney
Address
Medical Foundation Building
92-94 Parramatta Road, Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 263762 0
None
Name [1] 263762 0
Address [1] 263762 0
Country [1] 263762 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266629 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 266629 0
Ethics committee country [1] 266629 0
Australia
Date submitted for ethics approval [1] 266629 0
24/11/2014
Approval date [1] 266629 0
29/01/2015
Ethics approval number [1] 266629 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32319 0
Prof Anthony Keech and Alicia Jenkins
Address 32319 0
Medical Foundation Building 92-94 Parramatta Road Camperdown NSW 2050
Country 32319 0
Australia
Phone 32319 0
+61 2 9562 5000
Fax 32319 0
Email 32319 0
[email protected]
Contact person for public queries
Name 15566 0
Liping Li
Address 15566 0
Medical Foundation Building 92-94 Parramatta Road Camperdown NSW 2050
Country 15566 0
Australia
Phone 15566 0
+61 2 9562 5000
Fax 15566 0
Email 15566 0
[email protected]
Contact person for scientific queries
Name 6494 0
Alicia Jenkins
Address 6494 0
Medical Foundation Building 92-94 Parramatta Road Camperdown NSW 2050
Country 6494 0
Australia
Phone 6494 0
+61 2 9562 5000
Fax 6494 0
Email 6494 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers

• Data are potentially available to researchers from not-for-profit organisations based in any location. All data requests will be considered by the primary sponsor on a case by case basis.

Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires a data sharing agreement between data requester and trial custodian or sponsor

• Consent to provide case level data has not been obtained. IPD may be shared if a specific secondary research proposal receives a waiver of consent from our ethics committee. For further information, see our data sharing policy.

What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
After the study results are published and secondary researcher’s proposal has been approved by the data custodians. Data are available for an indefinite time.

To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• As of 1st July 2023, access can be requested via the Health Data Australia catalogue (https://www.researchdata.edu.au/health). Search for the ACTRN number in the catalogue to find datasets associated with this trial.

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Other https://ses.library.usyd.edu.au/handle/2123/31182  Data Dictionary


Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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