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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01320345




Registration number
NCT01320345
Ethics application status
Date submitted
18/03/2011
Date registered
22/03/2011
Date last updated
24/09/2019

Titles & IDs
Public title
The Fenofibrate And Microvascular Events in Type 1 Diabetes Eye.
Scientific 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.
Secondary ID [1] 0 0
ACTRN12611000249954
Secondary ID [2] 0 0
FAME0001
Universal Trial Number (UTN)
Trial acronym
FAME 1 EYE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus 0 0
Diabetic Retinopathy 0 0
Diabetic Nephropathies 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 0 0 0 0
Diabetes
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fenofibrate
Treatment: Drugs - Inert lactose placebo

Experimental: Fenofibrate - 145 mg tablet of fenofibrate administered daily for 36 months.

Placebo Comparator: Placebo - Inert lactose tablet (otherwise matching active) administered daily for 36 months.


Treatment: Drugs: Fenofibrate
145 mg tablet of fenofibrate administered once daily for 36 months.

Treatment: Drugs: Inert lactose placebo
Insert lactose tablet matching active tablet administered once daily for 36 months.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of clinical significant retinopathy progression. - Occurrence of clinical significant retinopathy progression, defined as a 2-step progression
Timepoint [1] 0 0
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 outcome [1] 0 0
Albuminuria. - Albuminuria measured as urinary albumin:creatinine ratio.
Timepoint [1] 0 0
At baseline, date of randomisation, 3 m post-randomisation, 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 outcome [2] 0 0
Visual acuity. - Visual acuity using Snellen Chart.
Timepoint [2] 0 0
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 outcome [3] 0 0
Corneal nerve damage. - 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] 0 0
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 outcome [4] 0 0
Estimated glomerular filtration rate. - Estimated glomerular filtration rate using Modification of Diet in Renal Disease (MDRD) formula.
Timepoint [4] 0 0
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 outcome [5] 0 0
Peripheral neuropathy status.sensation. - Peripheral neuropathy status assessed by temperature sensation and monofilament sensation.
Timepoint [5] 0 0
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 outcome [6] 0 0
Vascular function. - Vascular function using non-invasive pulse wave techniques and plethysmography.
Timepoint [6] 0 0
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 outcome [7] 0 0
Blood lipids and biomarkers in plasma. - Blood lipids and biomarkers in plasma.
Timepoint [7] 0 0
At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation) and wash-out visit.
Secondary outcome [8] 0 0
Total cardiovascular events. - Total cardiovascular events including myocardial infarction, stroke, sudden cardiac death, hospitalisation for acute coronary syndrome or any revascularisation events. These events are reported post-hoc by site to the sponsor.
Timepoint [8] 0 0
As reported throughout the study.
Secondary outcome [9] 0 0
Frequency of foot ulcer and non-traumatic amputation. - Frequency of foot ulcer and non-traumatic amputation. These events are reported post-hoc by site to the sponsor.
Timepoint [9] 0 0
On study completion.
Secondary outcome [10] 0 0
Macular volume. - Macular volume measured by Optical Coherence Tomography (OCT).
Timepoint [10] 0 0
On study completion.
Secondary outcome [11] 0 0
Autonomic neuropathy. - Autonomic neuropathy (QTc and R-R intervals) on annual ECGs.
Timepoint [11] 0 0
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 outcome [12] 0 0
Occurrence of clinically significant macula oedema (CSME). - Occurrence of clinically significant macula oedema (CSME) measured by optical coherence tomography and retinal photography.
Timepoint [12] 0 0
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 outcome [13] 0 0
Need for laser surgery. - Need for laser surgery measured by progression of retinopathy per standard ophthalmological assessment.
Timepoint [13] 0 0
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 outcome [14] 0 0
Need for intraocular anti-VEGF (vascular endothelial growth factor) injection. - Need for intraocular anti-VEGF (vascular endothelial growth factor) injection as per standard ophthalmological assessment.
Timepoint [14] 0 0
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 outcome [15] 0 0
Need for corticosteroid therapy. - Need for corticosteroid therapy to treat progressive retinopathy as per standard ophthalmological assessments.
Timepoint [15] 0 0
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 outcome [16] 0 0
Need for vitrectomy procedure. - Need for vitrectomy procedure as per standard ophthalmological assessment.
Timepoint [16] 0 0
At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
Garvan Institute of Medical Research - Darlinghurst
Recruitment hospital [4] 0 0
Retina Associates - South West Retina - Liverpool
Recruitment hospital [5] 0 0
Hunter Diabetes Centre - Merewether
Recruitment hospital [6] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [7] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [9] 0 0
Southern Adelaide Diabetes and Endocrine Services - Oaklands Park
Recruitment hospital [10] 0 0
Barwon Health - Geelong
Recruitment hospital [11] 0 0
Heidelberg Repatriation Hospital - Heidelberg
Recruitment hospital [12] 0 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment hospital [13] 0 0
St Vincent's Hospital Melbourne - Melbourne
Recruitment hospital [14] 0 0
Fremantly Hospital - Fremantle
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2291 - Merewether
Recruitment postcode(s) [6] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [7] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
5046 - Oaklands Park
Recruitment postcode(s) [10] 0 0
3220 - Geelong
Recruitment postcode(s) [11] 0 0
3081 - Heidelberg
Recruitment postcode(s) [12] 0 0
3004 - Melbourne
Recruitment postcode(s) [13] 0 0
3065 - Melbourne
Recruitment postcode(s) [14] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Juvenile Diabetes Research Foundation Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Mylan Pharmaceuticals
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01320345
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anthony Keech, Professor
Address 0 0
NHMRC Clinical Trials Centre, The University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Liping Li
Address 0 0
Country 0 0
Phone 0 0
+61 2 9562 5000
Fax 0 0
Email 0 0
fame1eye@ctc.usyd.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01320345