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Trial registered on ANZCTR


Registration number
ACTRN12615000497505
Ethics application status
Approved
Date submitted
28/04/2015
Date registered
19/05/2015
Date last updated
19/05/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Perhexiline effects on inflammatory activation and insulin sensitivity in diabetics or pre-diabetics with heart disease
Scientific title
Mechanism of action of perhexiline: expression of thioredoxin-interacting protein and insulin sensitivity in pre-diabetics or diabetics with cardiac disease
Secondary ID [1] 286592 0
nil
Universal Trial Number (UTN)
nil
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 294886 0
Cardiovascular 294887 0
Condition category
Condition code
Metabolic and Endocrine 295131 295131 0 0
Diabetes
Cardiovascular 295132 295132 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Perhexiline maleate
oral tablet
Dose: 600mg all at once on day 1, then 100mg twice daily from day 2 onwards for 14 days or dose adjusted depending on plasma drug concentration performed on day 2.
Plasma drug concentration is also to be repeated on day 14.
Intervention code [1] 291709 0
Treatment: Drugs
Comparator / control treatment
No control
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294894 0
Changes in platelet content of the pro-inflammatory protein thioredoxin-interacting protein (TXNIP). This would be assessed via immunohistochemical assay (Sverdlov et al, Int J of Cardiol. 2013; 168: 4624-4630).
Timepoint [1] 294894 0
two weeks after perhexiline therapy
Secondary outcome [1] 314294 0
Comparisons of extent of perhexiline effects with:
(1) Presence or absence of concomitant therapy with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, using analysis of variance.
(2) Plasma perhexiline concentrations. Correlations will be performed between plasma perhexiline concentrations and the extent of effects.
Timepoint [1] 314294 0
two weeks after perhexiline therapy
Secondary outcome [2] 314295 0
Plasma responsiveness to nitric oxide.
The nitric oxide donor sodium nitroprusside (10umol/L) will be used to quantitate platelet responsiveness to nitric oxide, with results being expressed as percentage of inhibition of aggregation induced by adenosine diphosphate (2.5umol/L) (Chirkov et al, Circulation 1999; 100: 129-134).
Timepoint [2] 314295 0
two weeks after perhexiline therapy
Secondary outcome [3] 314296 0
Insulin sensitivity, as measured using quantitative insulin-sensitivity check index (QUICKI) and homeostatic model assessment of insulin resistance (HOMA-IR).
Timepoint [3] 314296 0
two weeks after perhexiline therapy
Secondary outcome [4] 314513 0
Plasma assymmetric dimethylarginine concentrations, as measured by high performance liquid chromatography (Heresztyn T et al, J Chrom B Analyt Technol Biomed Life Sc, 2004; 805: 325-329).
Timepoint [4] 314513 0
two weeks after perhexiline therapy
Secondary outcome [5] 314514 0
Plasma thrombospondin-1 concentrations (R&D Systems Inc, Minneapolis, Minn).
Timepoint [5] 314514 0
two weeks after perhexiline therapy
Secondary outcome [6] 314515 0
Plasma myeloperoxidase concentrations, (assayed by Mercodia MPO Elisa kit, Sweden).
Timepoint [6] 314515 0
two weeks after perhexiline therapy
Secondary outcome [7] 314516 0
Plasma isoprostane, assayed by high performance liquid chromatography
Timepoint [7] 314516 0
two weeks after perhexiline therapy

Eligibility
Key inclusion criteria
1. Diabetes or pre-diabetes
2. Chronic cardiac disease to be treated with perhexiline, any of the following:
(a) myocardial ischaaemia
(b) refractory angina
(c) systolic heart failure
(d) severe symptomatic aortic stenosis
(e) hypertrophic cardiomyopathy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Less than 18 years old
2. Pregnancy, or women of childbearing age who are not using effective contraception
3. Concurrent treatment with any P2Y12 antagonist or perhexiline.


Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Diabetic or pre-diabetic patients who are clinically indicated for perhexiline therapy will be recruited: blood samples will be obtained at baseline and two weeks after perhexiline therapy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
No randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Analysis will be done comparing the effects before and after perhexiline; subgroup analysis will be performed to assess the effects of perhexiline in patients who have never receive ACE-inhibitor/ Angiotensin II receptor blocker
Phase
Phase 4
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
Sample size calculation is based on Sverdlov et al 2013 Int J Cardiol. In the previous study, 2-week of ramipril treatment reduces TXNIP from 286 +/- 20 (SEM) to 175 +/- 20 (SEM) in 15 patients. Therefore, in order to detect 25% change, n=30 will provide ~76% power at 0.5 SD.
Results will be compared by paired t-test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2014
Actual
7/04/2014
Date of last participant enrolment
Anticipated
31/12/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 3730 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 9603 0
5011 - Woodville South

Funding & Sponsors
Funding source category [1] 291158 0
Hospital
Name [1] 291158 0
Cardiology Department, The Queen Elizabeth Hospital
Country [1] 291158 0
Australia
Primary sponsor type
Hospital
Name
Cardiology Department, The Queen Elizabeth Hospital
Address
28, Woodville Road, Woodville South, 5011 South Australia.
Country
Australia
Secondary sponsor category [1] 289835 0
None
Name [1] 289835 0
Address [1] 289835 0
Country [1] 289835 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292734 0
Human Research Ethics Committee
Ethics committee address [1] 292734 0
Ethics committee country [1] 292734 0
Australia
Date submitted for ethics approval [1] 292734 0
23/01/2014
Approval date [1] 292734 0
03/04/2014
Ethics approval number [1] 292734 0
HREC/13/TQEHLMH/220

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

Contacts
Principal investigator
Name 56782 0
Prof John Horowitz
Address 56782 0
The Queen Elizabeth Hospital
28 Woodville Road, Woodville South, 5011 South Australia.
Country 56782 0
Australia
Phone 56782 0
61 8 82226000
Fax 56782 0
Email 56782 0
john.horowitz@adelaide.edu.au
Contact person for public queries
Name 56783 0
Cher-Rin Chong
Address 56783 0
The Queen Elizabeth Hospital
28 Woodville Road, Woodville South, 5011 South Australia.
Country 56783 0
Australia
Phone 56783 0
61 8 82226000
Fax 56783 0
Email 56783 0
cher-rin.chong@adelaide.edu.au
Contact person for scientific queries
Name 56784 0
John Horowitz
Address 56784 0
The Queen Elizabeth Hospital
28 Woodville Road, Woodville South, 5011 South Australia.
Country 56784 0
Australia
Phone 56784 0
61 8 82226000
Fax 56784 0
Email 56784 0
john.horowitz@adelaide.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.