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Trial registered on ANZCTR


Registration number
ACTRN12609000620224
Ethics application status
Approved
Date submitted
21/07/2009
Date registered
27/07/2009
Date last updated
1/07/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of pioglitazone and fish oils on the regulation of fat transport in subjects with the metabolic syndrome
Scientific title
The effect of pioglitazone and fish oils on the therapeutic regulation of lipid transport and hepatic steatosis in the metabolic syndrome
Secondary ID [1] 252140 0
PIFO
Universal Trial Number (UTN)
Trial acronym
PIFO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic syndrome 237310 0
Condition category
Condition code
Metabolic and Endocrine 239632 239632 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
4 parellel groups. Pioglitazone and Fish oils (Omacor) alone will be compared with a no treatment group and a combined Pioglitazone and Fish oils (Omacor) group.
Group 1. Pioglitazone alone 45mg oral tablets daily for a total of 12 weeks
Group 2. Fish oils (Omacor) alone 4 1000mg oral capsules daily for a total of 12 weeks
Group 3. Combined Pioglitazone 45mg oral tablets daily and Fish oils (Omacor) 4 1000mg oral capsules daily for a total of 12 weeks
Group 4. No treatment group
Intervention code [1] 236986 0
Treatment: Drugs
Comparator / control treatment
Comparators: Pioglitazone and Fish oils (Omacor
Control: no treatment
Control group
Active

Outcomes
Primary outcome [1] 238419 0
To examine the independent and combined effects of Pioglitazone and Fish Oils (Omacor) on Very Low Density Lipoprotein (VLDL) transport in metabolic syndrome subjects. VLDL transport will be used as an assessment tool of triglyceride transport. VLDL transport will be determined and compared between groups. All analysis will be carreid out using Statistical Package for the Social Sciences(SPSS). Differences between the four groups prior to randomization will be determined by one-way Analysis of Variance(ANOVA), after logarithmic transformation of skewed variables. Main and interactive treatment effects will be examined using general linear modelling adjusted for baseline covariates. Associations between kinetic estimates of lipid and lipoprotein, liver fat and other metabolic variables will be examined using simple and multiple linear regression methods. Compartmental analysis will be used to develop and fit models to lipid and lipoprotein tracer data.
Timepoint [1] 238419 0
VLDL transport time points are baseline, 5, 10, 20, 30, 40, 60mins, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0 hours following administration of D3-Leucine and D5-Glycerol stable isotopes on 2 occasions i.e. at the beginning and end of the treatment period.
Primary outcome [2] 238420 0
To examine the independent and combined effects of Pioglitazone and Fish Oils (Omacor) on VLDL-apolipoprotein B (apoB) production in metabolic syndrome subjects. VLDL-apoB production will be used as an assessment tool of apoB transport. VLDL-apoB production will be determined and compared between groups. All analysis will be carreid out using SPSS. Differences between the four groups prior to randomization will be determined by one-way ANOVA, after logarithmic transformation of skewed variables. Main and interactive treatment effects will be examined using general linear modelling adjusted for baseline covariates. Associations between kinetic estimates of lipid and lipoprotein, liver fat and other metabolic variables will be examined using simple and multiple linear regression methods. Compartmental analysis will be used to develop and fit models to lipid and lipoprotein tracer data.
Timepoint [2] 238420 0
VLDL-apoB production time points are baseline, 5, 10, 20, 30, 40, 60mins, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0 hours following administration of D3-Leucine and D5-Glycerol stable isotopes on 2 occasions i.e. at the beginning and end of the treatment period.
Secondary outcome [1] 244897 0
To examine the independent and combined effects of Pioglitazone and Fish Oils (Omacor) on liver fat in metabolic syndrome subjects. Liver fat content will be used as an assessment tool of fat storage in the liver. Liver fat will be determined and compared between groups. All analysis will be carreid out using SPSS. Differences between the four groups prior to randomization will be determined by one-way ANOVA, after logarithmic transformation of skewed variables. Main and interactive treatment effects will be examined using general linear modelling adjusted for baseline covariates. Associations between kinetic estimates of lipid and lipoprotein, liver fat and other metabolic variables will be examined using simple and multiple linear regression methods. Compartmental analysis will be used to develop and fit models to lipid and lipoprotein tracer data.
Timepoint [1] 244897 0
Liver fat will be measured by magnetic resonance imaging and magnetic resonance spectroscopy on two occasions i.e. at the beginning and end of the treatment period.

Eligibility
Key inclusion criteria
Non-smoking men aged 18-75 years and post menopausal women aged =75 years will be recruited. In this study we will define the metabolic syndrome on a composite of published criteria: waist circumference >94cm for men and >80cm for women, triglycerides >1.7mmol/L and/or High Density Lipoprotein (HDL)-cholesterol <1.0mmol/L, and Homeostais assessment (HOMA) score >2.5 (>75th percentile of a reference range). To define hepatic steatosis, we will select only metatbolic syndrome subjects with Alanine transaminase (ALT) levels >20U/L.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects with diabetes mellitus (fasting plasma glucose >7.0mmol/L), genetic hyperlipidaemia (e.g. Familial Hypercholesterolaemia), hypothyroidism, cholelithiasis; alcohol excess (>20g/day); proteinuria, creatinaemia (>130umol/L), hepatic dysfunction (Aspartate transaminase (AST) or ALT > 3x upper limit of normal (ULN); muscle disorders or creatinine kinase (>3xULN); major systemic illness or use of steroids or other agents that may influence lipid metabolism; cardiovascular event within the last six months, New York Heart Association (NYHA) class III/IV heart failure; anaemia, osteoporosis and pregnancy: patients on hypocaloric diets;. These exclusions have been defined to limit factors that may influence lipoprotein metabolism and introduce error in testing the hypothesis.

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)
Allocation involves contacting the person holding the allocation schedule and who is not involved in the study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomised sequence generated by computer
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
24/08/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 237370 0
Government body
Name [1] 237370 0
National Health and Research Council (NHMRC) grant, University of Western Australia.
Country [1] 237370 0
Australia
Primary sponsor type
Individual
Name
Professor Gerald Watts
Address
School of Medicine and Pharmacology
Royal Perth Hospital,
Rear 50 Murray Street,
PO Box X2213, Perth,
WA 6847
Country
Australia
Secondary sponsor category [1] 236866 0
None
Name [1] 236866 0
Address [1] 236866 0
Country [1] 236866 0
Other collaborator category [1] 782 0
Individual
Name [1] 782 0
Dr Dick Chan
Address [1] 782 0
School of Medicine and Pharmacology
Royal Perth Hospital,
Rear 50 Murray Street,
PO Box X2213, Perth,
WA 6847
Country [1] 782 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239502 0
Royal Perth Hospital Ethics Committee
Ethics committee address [1] 239502 0
Royal Perth Hospital, Wellington Street, PO Box X2213, Perth, WA 6847
Ethics committee country [1] 239502 0
Australia
Date submitted for ethics approval [1] 239502 0
05/05/2009
Approval date [1] 239502 0
16/07/2009
Ethics approval number [1] 239502 0
2009/050

Summary
Brief summary
The aim of this study is to examine the independent and combined effects of Pioglitazone and Omacor (fish oil) on VLDL transport in metabolic syndrome subjects with non-alcoholic fatty liver disease (NAFLD). NAFLD, which afflicts 20-30% of our population, increases the risk of cardiovascular disease (CVD) and is related to a higher prevalence of insulin resistance, obesity and dyslipidaemia, key characteristics of the metabolic syndrome. Eligible participants will be randomised to one of 4 groups: Pioglitazone alone, Omacor alone, combined Pioglitazone and Omacor, or usual care, that is, no additional treatment or placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29937 0
Address 29937 0
Country 29937 0
Phone 29937 0
Fax 29937 0
Email 29937 0
Contact person for public queries
Name 13184 0
Sandra Hamilton
Address 13184 0
School of Medicine and Pharmacology, Royal Perth Hospital, Rear 50 Murray Street, PO Box X2213, Perth, WA 6847
Country 13184 0
Australia
Phone 13184 0
+61 8 9224 0318
Fax 13184 0
+61 8 9224 0243
Email 13184 0
[email protected]
Contact person for scientific queries
Name 4112 0
Dr Dick Chan
Address 4112 0
School of Medicine and Pharmacology, Royal Perth Hospital, Rear 50 Murray Street, PO Box X2213, Perth, WA 6847
Country 4112 0
Australia
Phone 4112 0
+61 8 9224 0268
Fax 4112 0
+61 8 9224 0246
Email 4112 0
[email protected]

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