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Trial registered on ANZCTR


Registration number
ACTRN12609000053224
Ethics application status
Approved
Date submitted
17/01/2009
Date registered
23/01/2009
Date last updated
4/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Potential therapy for left ventricular hypertrophy in diabetic heart disease
Scientific title
Pilot study of the effects on cardiac diastolic function of GC811007, a fructosamine oxidase inhibitor, in patients with Type 2 diabetes and diabetic cardiomyopathy
Universal Trial Number (UTN)
Trial acronym
INFO-CARDIAC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Left-ventricular hypertrophy in type-2 diabetic patients 4210 0
Condition category
Condition code
Metabolic and Endocrine 4425 4425 0 0
Diabetes
Cardiovascular 4426 4426 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral administration of trientine[Triethylenetetramine dihydrochloride] 600 mg twice daily p.o. (two 300 mg capsules twice daily) before breakfast and
evening meal.
Duration period: 12 months.
Intervention code [1] 3925 0
Treatment: Drugs
Comparator / control treatment
Placebo: Equivalent weight of microcellulose contained in identical capsules.
Mode of administration of placebo: Identical to that of active drug, namely
600 mg twice daily p.o. (two 300 mg capsules twice daily) before breakfast
and evening meals.
Duration of placebo dose: 12 months.
Control group
Placebo

Outcomes
Primary outcome [1] 5306 0
left ventricle mass indexed to body surface area (LVMbsa) after six and 12 months of therapy as determined by cardiac
magnetic resonance imaging (cMRI).
Timepoint [1] 5306 0
at baseline and at 6, 12 months after randomisation
Primary outcome [2] 5307 0
Change in early mitral annular velocity (Em) as determined by echocardiography (ECHO)
Timepoint [2] 5307 0
at baseline and at 6 months after randomisation
Primary outcome [3] 5308 0
Change in LV apical rotation at 140% of systole as determined by cMRI
Timepoint [3] 5308 0
at baseline and at 6, 12 months after randomisation
Secondary outcome [1] 8928 0
Change in urinary copper excretion
Timepoint [1] 8928 0
after four months

Eligibility
Key inclusion criteria
Age between 30 and 70 years; known type 2 diabetes; HbA1c > 7.0% at enrollment; normal electrocardiogram; abnormal diastolic filling as demonstrated by mitral inflow Doppler with pre-load reduction LV ejection fraction = 45% by echocardiography, with evidence of diastolic dysfunction but no regional wall-motion abnormalities; no new medications for six months prior to randomization with no change of ß-blocker dose during that period.
Minimum age
30 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Morbid obesity (BMI = 45 kg.m-2); type 1 diabetes; history or evidence of diabetic retinopathy and/or diabetic nephropathy (serum creatinine > 150 µmol/l and/or urinary albumin > 300 mg/l); autonomic neuropathy; significant cardiac valvular disease; LV wall motion abnormality by echocardiography; history of significant malabsorption; multiple drug allergies; use or misuse of substances of abuse; evidence of abnormal electrolyte homeostasis or renal, hepatic or thyroid function; or standard contraindications to MRI

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)
This was a double blind randomized trial. Patients enrolled from a hospital clinic in Auckland, NZ following completion of written consent. Prior to randomization to treatment, patients completed a 4 week single-blind run-in period of 2 placebo capsules twice daily, for which = 90% compliance was required for progression into the trial. Patients meeting inclusion criteria then randomized to receive trientine or identical placebo capsules. Treatment
assignment was performed centrally using variable block sizes to ensure
balance throughout trial recruitment and numbered drug packs were
prepared and dispensed sequentially to randomized patients
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random order of subject enrollment into treatment groups without stratification was performed by permuted block randomisation to ensure balance throughout enrollment, using a computer software programme contained with SAS v8.01 (SAS Institute, Cary, NC, USA)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 1538 0
New Zealand
State/province [1] 1538 0
Auckland

Funding & Sponsors
Funding source category [1] 4391 0
Commercial sector/Industry
Name [1] 4391 0
Protemix Corporation
Address [1] 4391 0
P O Box 2165
Auckland 1140
Country [1] 4391 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Protemix Corporation
Address
P O Box 2165
Auckland 1140
Country
New Zealand
Secondary sponsor category [1] 3951 0
None
Name [1] 3951 0
Address [1] 3951 0
Country [1] 3951 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6438 0
Auckland Ethics Committee
Ethics committee address [1] 6438 0
650 Great South Road,
Penrose,
Auckland 1061
Ethics committee country [1] 6438 0
New Zealand
Date submitted for ethics approval [1] 6438 0
Approval date [1] 6438 0
15/12/2000
Ethics approval number [1] 6438 0
2000/188

Summary
Brief summary
This study was designed to assess the effects of the drug triethylenetetramine dihydrochloride on cardiac dysfunction in patients with type 2 diabetes (T2DM) and demonstrable cardiac dysfunction. Previous treatment of diabetic rats has shown significant improvement in structure and function of the heart, including alleviation of heart failure through significant cardiac regeneration, and clinical studies have shown that TETA.2HCl may work through chelation and excretion of copper (Cu) in urine. This study was designed to measure indices of cardiac structure over a 12 month intervention period and hypothesized that markers of diastolic dysfunction in T2DM would be improved on treatment versus placebo.
Trial website
Trial related presentations / publications
Diabetologia, MS 08 1484 in final edit
Public notes

Contacts
Principal investigator
Name 35098 0
Address 35098 0
Country 35098 0
Phone 35098 0
Fax 35098 0
Email 35098 0
Contact person for public queries
Name 12445 0
Associate-Professor Sally Poppitt
Address 12445 0
School of Biological Sciences,
University of Auckland
Private Bag 92 109
Auckland 1142
Country 12445 0
New Zealand
Phone 12445 0
+64 (09) 6305160
Fax 12445 0
+64 (9) 373 7045
Email 12445 0
s.poppitt@auckland.ac.nz
Contact person for scientific queries
Name 3373 0
Professor Garth Cooper
Address 3373 0
School of Biological Sciences,
University of Auckland
Private Bag 92 109
Auckland 1142
Auckland
Country 3373 0
New Zealand
Phone 3373 0
+64 (9) 373 7599 Ext 87394
Fax 3373 0
+64 (9) 373 7045
Email 3373 0
g.cooper@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary