Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001188527
Ethics application status
Approved
Date submitted
26/10/2015
Date registered
4/11/2015
Date last updated
5/02/2021
Date data sharing statement initially provided
5/02/2021
Date results information initially provided
5/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Modulation of Plasmalogens in Human Males using Alkylglycerol
Scientific title
Modulation of Plasmalogens in Human Males using Alkylglycerol
Secondary ID [1] 287405 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atherosclerosis 296110 0
Diabetes 296643 0
Obesity 296644 0
Condition category
Condition code
Cardiovascular 296369 296369 0 0
Other cardiovascular diseases
Metabolic and Endocrine 296872 296872 0 0
Diabetes
Alternative and Complementary Medicine 296873 296873 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In this project we will observe the effect of alkylglycerol (Alkyrol) supplementation (in the form of a capsule) on overweight/obese males. The study will involve a cross-over design, where participants will take a supplement of Alkyrol (shark liver oil capsule) or placebo (dummy capsule) for three weeks, a wash out (no supplementation) period of three weeks and cross over to Alkyrol or placebo for three weeks. Over this time blood will be collected at certain points and then analysed to observe the effect of alkylglycerol on plasmalogens and the effect of inflammation.

Alkyrol will be administered 2g twice daily, the maximum recommended dose (4g daily). Any unused capsules will be asked to be returned between treatments. Blood tests will be done before and after each treatment arm to monitor participants.
Intervention code [1] 293119 0
Treatment: Other
Comparator / control treatment
The placebo used in this study is Methylcelullose
Control group
Placebo

Outcomes
Primary outcome [1] 296017 0
Circulating plasmalogens as determined by mass spectrometric analysis of plasma
Timepoint [1] 296017 0
The study is a cross over, double blind placebo controlled study design. Circulating plasmalogens will be measured one day before and one day after each treatment period (placebo and alkylglycerol) as well as at recruitment. In total five measurements of circulating plasmalogens will be made.
Secondary outcome [1] 317238 0
Secondary outcomes of the effect of alkylglycerol are; plasma lipids (total cholesterol, HDL-C, LDL-C, triglycerides.
Timepoint [1] 317238 0
Secondary outcome variables will be measured one day before and one day after each treatment period (placebo and alkylglycerol) as well as at recruitment. In total five measurements of secondary outcome variables will be made.
Secondary outcome [2] 318499 0
fasting plasma glucose
Timepoint [2] 318499 0
one day before and one day after each treatment period
Secondary outcome [3] 318500 0
Plasma oxidiative markers (TBARS, thiobarbituric acid reactive substances)
Timepoint [3] 318500 0
One day before and one day after each treatment period
Secondary outcome [4] 318501 0
Plasma inflammatory markers (hsCRP, MCP-1, VCAM-1 and TNF-alpha)
Timepoint [4] 318501 0
One day before and one day after each treatment period
Secondary outcome [5] 318502 0
Full lipidomic profile of plasma. Performed by mass spectrometric analysis of over 400 plasma lipids using only 10 uL plasma.
Timepoint [5] 318502 0
One day before and one day after each treatment period

Eligibility
Key inclusion criteria
Males aged 25-60 years; BMI between 28 and 40 (kg/m2); no evidence of established diabetes or cardiovascular disease. Not on any lipid lowering or antihypertensive medication, not taking any fish oil supplementation; normal liver function; have given signed informed consent to participate in the study.
Minimum age
25 Years
Maximum age
60 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Established diabetes or cardiovascular disease, on any prescription medication, fish oil supplements, evidence of liver disease (i.e. cirrhosis or hepatitis) or abnormal liver function defined as aspartate aminotransferase, alanine aminotransferase or total bilirubin >1.5x the upper limit of normal.

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)
The clinical trials pharmacy:
*will allocate the randomisation numbers according to the order of participant eligibility.
*Akyrol and Placebo will be encapsulated to look the same and will be dispensed into containers
*Randomised schedule and numbers will be generated via excel
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The clinical trials pharmacy:
*will generate an electronic randomisation schedule with randomisation numbers and corresponding drug treatments using Microsoft excel program
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power calculations are based on the primary endpoint of circulating plasmalogen concentrations. To our knowledge the current proposal will be the first to use alkrol to specifically increase circulating molecular species of plasmalogen.
We have performed lipid profiling on several human cohorts (plasma) and the variation in lipid concentrations is typically in the order of 20%. Sample sizes of 10 will allow us to detect a mean 20% change in the plasmalogen levels with a significance of 0.05 at a power of 0.80. To detect a difference in circulating plasmalogens between the active and placebo arms of the study, 10 participants would provide a power of 80% at an a=0.05 to detect a 20% difference in specific plasmalogen species.
The change in plasma lipids and other parameters measured will be compared between active and placebo treatments using repeated measures analysis of variance (ANOVA). Comparisons between treatments will include treatment order as a between-subject variable. Individual mean comparisons will be made using appropriate post-hoc testing performed where ANOVAs are significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/11/2015
Actual
8/12/2015
Date of last participant enrolment
Anticipated
Actual
24/05/2016
Date of last data collection
Anticipated
Actual
8/08/2016
Sample size
Target
10
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 291972 0
Other
Name [1] 291972 0
Baker IDI Heart and Diabetes Research Institute
Country [1] 291972 0
Australia
Primary sponsor type
Other
Name
Baker IDI Heart and Diabetes Research Institute
Address
75 Commercial Road,
Melbourne, Vic
3004
Country
Australia
Secondary sponsor category [1] 290639 0
None
Name [1] 290639 0
Address [1] 290639 0
Country [1] 290639 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293467 0
Alfred HREC
Ethics committee address [1] 293467 0
Office of Ethics and Research Governance
Ground Floor, Linay Pavillion,
The Alfred Hospital
Commercial Road,
Melbourne, Vic
3004
Ethics committee country [1] 293467 0
Australia
Date submitted for ethics approval [1] 293467 0
02/09/2015
Approval date [1] 293467 0
26/10/2015
Ethics approval number [1] 293467 0
436/15

Summary
Brief summary
In previous studies, we and others have observed that the levels of plasmalogens (a class of phospholipid (blood fat)) are lower in obese people and people with type 2 diabetes and cardiovascular (heart) disease. In one of our studies we have shown that dietary supplementation of alkylglycerol (fats found in the liver of most animals and fish) can increase levels of plasmalogens. This increase is associated with a reduction of athersosclerosis (artery blockage) in mice. In separate experiments, after treating mice on a high fat diet with alkylglycerols, we observed a reduction in the inflammation caused by obesity.

In this project we will observe the effect of alkylglycerol (Alkyrol) supplementation (in the form of a capsule) on overweight/obese males. The study will involve a cross-over design, where participants will take a supplement of Alkyrol (shark liver oil capsule) or placebo (dummy capsule) for three weeks, a wash out (no supplementation) period of three weeks and cross over to Alkyrol or placebo for three weeks. Over this time blood will be collected at certain points and then analysed to observe the effect of alkylglycerol on plasmalogens and the effect of inflammation.

We will recruit 10 overweight/obese men (Body Mass Index (BMI – a measure of body fat based in relation to your height) of 28-35kg/m2), not being treated for hypertension (high blood pressure), diabetes or cardiovascular (heart) disease or taking any fish oil supplements.

This study represents the first proof of concept (demonstration) human trial that alkylglycerols can modify circulating plasmalogen levels and influence inflammation. If positive, this randomised clinical trial will support therapeutic approaches targeting plasmalogen modification for the prevention of type 2 diabetes and cardiovascular disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60042 0
A/Prof Peter Meikle
Address 60042 0
Baker IDI Heart and Diabetes Research Institute
75 Commercial Road,
Melbourne Vic 3004
Country 60042 0
Australia
Phone 60042 0
+61 3 8532 1770
Fax 60042 0
+61 3 8532 1100
Email 60042 0
[email protected]
Contact person for public queries
Name 60043 0
Mrs Michelle Cinel
Address 60043 0
Baker IDI Heart and Diabetes Research Institute
75 Commercial Road,
Melbourne Vic 3004
Country 60043 0
Australia
Phone 60043 0
+61 3 8532 1229
Fax 60043 0
+61 3 8532 1100
Email 60043 0
[email protected]
Contact person for scientific queries
Name 60044 0
A/Prof Peter Meikle
Address 60044 0
Baker IDI Heart and Diabetes Research Institute
75 Commercial Road,
Melbourne Vic 3004
Country 60044 0
Australia
Phone 60044 0
+61 3 8532 1770
Fax 60044 0
+61 3 8532 1100
Email 60044 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.