Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000177358
Ethics application status
Approved
Date submitted
30/01/2017
Date registered
2/02/2017
Date last updated
2/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Omega-3 fish oil for the prevention of Gestational Diabetes
Scientific title
Omega-3 fish oil for the prevention of gestational diabetes: a double-blind, randomized controlled proof of concept study
Secondary ID [1] 290246 0
Nil known
Universal Trial Number (UTN)
U1111-1192-1425
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gestational Diabetes 300454 0
Condition category
Condition code
Reproductive Health and Childbirth 300312 300312 0 0
Fetal medicine and complications of pregnancy
Diet and Nutrition 300313 300313 0 0
Other diet and nutrition disorders
Metabolic and Endocrine 301513 301513 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2 x 1g fish oil capsules each day (each capsule containing 60mg eicosapentaenoic acid and 430mg docohexaenoic acid) from ~ 14 weeks gestation until 34 weeks gestation. Adherence to trial protocol will be assessed using a capsule log, return capsule count, and erythrocyte fatty acid composition.
Intervention code [1] 296990 0
Prevention
Comparator / control treatment
1 x 1g corn oil capsules/day from ~ 14 weeks gestation until 34 weeks gestation.
Control group
Placebo

Outcomes
Primary outcome [1] 300879 0
Insulin Resistance, as measured by HOMA-IR (fasting glucose x fasting insulin / 22.5)
Timepoint [1] 300879 0
14, 20, 28 & 34 weeks gestation
Secondary outcome [1] 331099 0
Plasma inflammatory markers (IL-6, TNF-alpha, CRP, IL-1beta) and adipokines (adiponectin, leptin), measured using ELISA assays.
Timepoint [1] 331099 0
14, 20 and 34 weeks gestation
Secondary outcome [2] 331100 0
Blood Pressure
Timepoint [2] 331100 0
14, 20 and 34 weeks gestation
Secondary outcome [3] 331103 0
Newborn whole-blood fatty acid composition
Timepoint [3] 331103 0
Post delivery (48-72 hours after birth)
Secondary outcome [4] 331104 0
Matsuda Index (Calculated from 2 hour oral glucose tolerance test)
Timepoint [4] 331104 0
28 weeks gestation
Secondary outcome [5] 331144 0
Erythrocyte fatty acid composition, measured by gas chromatography from a fasting blood sample
Timepoint [5] 331144 0
14, 20 & 34 weeks gestation

Eligibility
Key inclusion criteria
<14 weeks pregnant
Aged 18-40
Any one of the following:
a) PAPP-A between 0.3 and 0,6 MoM in their Nuchal Translucency Scan
b) previous history of gestational diabetes
c) at risk of developing gestational diabetes according to Health pathway criteria
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
BMI greater than 45kg/m2
Any incidence of ongoing bleeding beyond 8 weeks gestation in the current pregnancy
Is on anti-coagulant therapy or known to have clotting disorders
Known to be pregnant with multiples
Lactating
Established diabetes prior to pregnancy or currently taking anti-diabetic medications
Being diagnosed with gestational diabetes in this pregnancy prior to enrolment in the study
Known allergies to seafood or corn
Currently on medication with Aspirin and Warfarin
Has significant current gastro-intestinal disease
Is incapable of giving informed consent
History of new investigational drug three months prior to this trial
Currently consuming more than 200g oily fish per week or taking supplements delivering 150mg or more of DHA/day
Unable to fast for 10hr before obtaining blood sample

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be allocated to group A or group B. Group allocation will be conducted by someone not associated with this study, and the group allocation will be sealed in 2 x opaque envelopes until data analysis has been completed. The sealed envelope will kept by the person responsible for blinding and one copy with the Chief Investigator, should the need for unblinding arise.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization sequence will be a computer-generated random sequence
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: This pilot study has been powered to determine whether DHA supplementation has a measurable effect on measures of insulin resistance in pregnancy. Therefore the alpha has been set at 0.1, and power at 80%. A significance level of 10% was chosen to reflect a greater priority of reducing type 2 errors over type 1 errors as this is a proof of concept study. Previous studies have shown that the standard deviation of HOMA-IR is around 1.0 units (Endo et al, 2006; Lacroix et al, 2013), and a 0.5 unit difference in HOMA-IR has clinical significance. 32 participants per group in a parallel design will give an 80% power to detect a 0.5 unit difference in HOMA-IR between intervention and placebo groups at 28-weeks, assuming a standard deviation of 1.0 and an alpha set at 0.1. To allow for drop-outs, 37 will be recruited to each group, giving a total of 74 participants.

Baseline data: Baseline outcome measures will be used as covariates. BMI and other potentially confounding variables such as age may be added as covariates if there appears to be an imbalance between the treatment arms.
Treatment effects: All the data relating the significant effects of n-3PUFA are expressed as mean +/- SEM or median (IQR) as appropriate. The effect of interventions on glucose tolerance, HOMA-IR and blood glucose levels between groups will be estimated by using two-way ANOVA with post hoc comparisons (Tukey’s honestly significant difference). With-in group effects will be assessed using one-way ANCOVA with repeated measures or Friedman test if assumptions for ANCOVA are violated. Differences in the proportion of pregnancies that develop gestational diabetes in each group will be assessed using Chi Square or Fisher’s Exact test as appropriate.
P-values less than 0.1 indicate statistically significant between- treatment group differences in outcome values.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
74
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7391 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 15185 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 295446 0
University
Name [1] 295446 0
University of Newcastle
Country [1] 295446 0
Australia
Funding source category [2] 295469 0
Commercial sector/Industry
Name [2] 295469 0
EPAX
Country [2] 295469 0
Norway
Primary sponsor type
University
Name
The University of Newcastle
Address
University Drive, Callaghan, NSW, 2308
Country
Australia
Secondary sponsor category [1] 294291 0
None
Name [1] 294291 0
Address [1] 294291 0
Country [1] 294291 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296777 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 296777 0
Locked Bag 1
New Lambton, NSW, 2305
Ethics committee country [1] 296777 0
Australia
Date submitted for ethics approval [1] 296777 0
19/10/2016
Approval date [1] 296777 0
13/12/2016
Ethics approval number [1] 296777 0
2016/10/19/3.03
Ethics committee name [2] 296778 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [2] 296778 0
University Drive
Callaghan
NSW, Australia, 2308
Ethics committee country [2] 296778 0
Australia
Date submitted for ethics approval [2] 296778 0
09/12/2016
Approval date [2] 296778 0
13/01/2017
Ethics approval number [2] 296778 0
H-2017-0012

Summary
Brief summary
Gestational diabetes (GD) is a form of diabetes which occurs during pregnancy, and generally resolves after delivery. It is diagnosed as high blood glucose during pregnancy, and affects around 5–10% of all pregnancies in Australia. Recent changes to diagnostic criteria along with an increasingly obese population and older age at which women have their first child, mean the prevalence of GD is rapidly rising. Pregnancy is known to be an insulin-resistant state, and failure to adequately compensate for this inherent insulin resistance through increased insulin secretion results in hyperglycaemia. Whilst the precise mechanisms behind this insulin resistant state are unclear, there is increasing evidence that inflammation of adipose tissue is associated with GD development. Pregnancy is characterized by adipose tissue remodeling and growth, which is modulated by inflammatory markers. However, higher levels of inflammatory markers such as IL-6 and TNF-a, and lower levels of adiponectin are associated with the development of GD.
Docosahexaenoic Acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3PUFA) that is critical to the neural development of the foetus during pregnancy, and may be beneficial to adipose tissue functioning during pregnancy. Pregnancies complicated by type 2 diabetes and GD are associated with a decline in erythrocyte DHA in late pregnancy when compared with normoglycaemic pregnancies. This fall can be ameliorated by DHA supplementation during pregnancy. Supplementation of n-3PUFAs in pregnancies affected by GD confers beneficial effects on insulin resistance when compared with control groups Furthermore, supplementation of EPA + DHA from weeks 10-16 of pregnancy until term results in reduced expression of IL-6, IL-8 and TNF-a in both adipose and placental tissue. The improved insulin sensitivity and adipokine profile and reduced levels of inflammatory markers suggest improved adipose tissue function in response to n-3PUFA supplementation, which could reduce the risk of developing GD.
To date, research investigating the relationship between n-3PUFAs and GD as an outcome have not reported a relationship. However, supplementation in these trials commenced later in the second trimester, from 17 weeks’ gestation, with the majority not commencing until 24 weeks gestation. We postulate this is too late in pregnancy as GD has often become apparent by this point. No research has reported the effect of an n-3PUFA intervention in early pregnancy on insulin resistance, adipokines and markers of inflammation.
We hypothesize that DHA supplementation supports healthy adipose tissue development and functioning during pregnancy, and this in turn reduces the risk of developing gestational diabetes. The aim of the current study is to determine the effect of a low-dose DHA-enriched n-3PUFA supplement on measures of insulin resistance, adipokine profile and inflammatory markers from early pregnancy in women at high risk of developing GD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69378 0
Prof Manohar Garg
Address 69378 0
305C Medical Sciences Building
University of Newcastle
University Drive,
Callaghan, NSW, 2308
Country 69378 0
Australia
Phone 69378 0
+61 2 4921 5647
Fax 69378 0
+61 2 4921 2018
Email 69378 0
[email protected]
Contact person for public queries
Name 69379 0
Ms Kylie Abbott
Address 69379 0
305B Medical Sciences Building
University of Newcastle
University Drive,
Callaghan, NSW, 2308
Country 69379 0
Australia
Phone 69379 0
+61 2 4921 5638
Fax 69379 0
Email 69379 0
[email protected]
Contact person for scientific queries
Name 69380 0
Prof Manohar Garg
Address 69380 0
305C Medical Sciences Building
University of Newcastle
University Drive,
Callaghan, NSW, 2308
Country 69380 0
Australia
Phone 69380 0
+61 2 4921 5647
Fax 69380 0
Email 69380 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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