Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001006336
Ethics application status
Approved
Date submitted
19/06/2017
Date registered
12/07/2017
Date last updated
12/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Measuring the absorption of gangliosides from cows milk in healthy women of child bearing age.
Scientific title
Exploring in vivo dynamics of bovine milk derived gangliosides in healthy women of child bearing age.
Secondary ID [1] 292072 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Investigating/measuring bio-availability/absorption of gangliosides 303485 0
Condition category
Condition code
Diet and Nutrition 302899 302899 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A diurnal variation study will be conducted involving the monitoring of plasma gangliosides over the course of a day and from day-to-day; a randomised controlled acute trial will investigate the kinetics of uptake in plasma of gangliosides after consumption of a high vs. a low ganglioside meal and samples collected during the acute feeding trial will be used to validate the finger prick (Guthrie card) dried blood spot gangliosides against plasma gangliosides.

The study will comprise of 3 clinic visits:

Visit 1: Participants (n=33, randomly selected from total sample of 66) will present at the CSIRO clinic between 7 and 9 am after an overnight fast and remain at the clinic for the next 2 hours. Participants will have an IV cannula inserted for the duration of this visit. A fasting blood sample will be collected after which participants will be provided with a high ganglioside meal (200 mL of a dairy based milk drink) . Blood samples will be collected after 1 h and 2h.

Visit 2 (7 days post baseline visit): Participants will follow their habitual diet for 7 days and present at the CSIRO clinic between 7 and 9 am after an overnight fast (from 8 pm) and remain at the clinic for the next 8 hours. Participants will have an IV cannula inserted for the duration of this visit. A fasting blood sample will be collected after which participants will be provided with a high ganglioside meal (200 mL of a dairy based milk drink). For the remainder of the day the participants will remain in the clinic and consume low ganglioside snacks/meals (breakfast - 8 am, lunch – 12.30 pm as well as mid-morning -10 am and mid-afternoon snacks -2.30 pm, times at which meals/snacks are consumed may vary by 30 minutes to that listed to accommodate staggering of blood sampling from all study participants). Low ganglioside meals consumed throughout the day will consist of fruit and nut snacks and a choice from Pumpkin soup, Fettuccine with Garlic, Tomatoes & Olives, Fragrant Vegetable Curry or Vegan Fried Rice as main meals. Blood samples will be collected after 1h, 2h, 4h, 6h and 8h. Fasting samples from this visit will be compared to fasting samples from visit 3 to see how ganglioside concentrations change after following a low ganglioside diet for 1 week.

Visit 3 (14 days post baseline visit): The acute ganglioside intervention will be conducted using a randomised parallel study design. During the week preceding the test day participants will be requested to consume a low ganglioside diet (vegan diet, since gangliosides are only found in animal-derived foods). Dietitians will specifically design this dietary pattern and counsel the participants through this eating pattern. Participants will be provided with approximately 30 % of foods/vouchers and a shopping list to enhance compliance. Compliance to the diets will be assessed through a compliance checklist which will require participants to indicate if they consumed any “disallowed foods”. Participants will be asked to check yes/no against a range of food categories e.g. milk, cheese, meat etc. In the instance of consumption of any “disallowed foods” the participant will be asked to provide details about the type/amount of food/s consumed. This compliance checklist will be reviewed by the dietitian at visit 3.

On the test day participants will be fasted from 8 pm the previous night, presenting at the CSIRO clinic between 7 and 9 am and remain at the clinic for the next 8 hours. Participants will be randomly assigned to treatments including consumption of a high ganglioside meal (200 mL of a dairy based milk drink) or a low ganglioside meal (200 mL of a Soy milk drink) Participants will have IV cannula inserted for the duration of the visit. A fasting blood sample will be collected after which participants will consume the test meal within 15 minutes. Blood samples will be collected after 0.5h, 1h, 2h, 4h, 6h, 8h. During the day participants will consume low ganglioside, low fat snacks and meals as described for visit 2 of the study.

The high ganglioside intervention will consist of bovine milk with added gangliosides in powder form to deliver 80 mg gangliosides per meal (200 mL in total volume). The low ganglioside intervention will consist of non-bovine flavoured milk devoid of gangliosides. Soy milk is the most nutritionally comparable to bovine milk (200 mL in total volume to also be consumed). Participants will be requested to maintain their habitual lifestyle patterns for the duration of the study unless otherwise specified.
Intervention code [1] 298211 0
Lifestyle
Intervention code [2] 298389 0
Prevention
Intervention code [3] 298448 0
Treatment: Other
Comparator / control treatment
The control group (low ganglioside meal) will consist of non-bovine flavoured milk devoid of gangliosides. Soy milk is the most nutritionally comparable to bovine milk.
Control group
Active

Outcomes
Primary outcome [1] 302477 0
Blood plasma gangliosides measured by Mass Spectrometry
Timepoint [1] 302477 0
Visit 1
T0 (Baseline)

T1 (60 minutes post consumption of high ganglioside milk drink)

T2 (120 minutes post consumption of high ganglioside milk drink)



Visit 2 (7 days post baseline visit)
T0 (Baseline)

T1 ( 60 minutes post consumption of high ganglioside milk drink)

T2 (120 minutes post consumption of high ganglioside milk drink)

T3 (240 minutes post consumption of high ganglioside milk drink)

T4 (360 minutes post consumption of high ganglioside milk drink)

T5 (480 minutes post consumption of high ganglioside milk drink)



Visit 3 (14 days post baseline visit)
T0 (Baseline)

T1 (30 minutes post consumption of low/ high ganglioside milk drink)

T2 (60 minutes post consumption of low/ high ganglioside milk drink)

T3 (120 minutes post consumption of low/ high ganglioside milk drink)

T4 (240 minutes post consumption of low/ high ganglioside milk drink)

T5 (360 minutes post consumption of low/ high ganglioside milk drink)

T6 (480 minutes post consumption of low/ high ganglioside milk drink)
Primary outcome [2] 302664 0
Dried blood spot (finger-prick derived blood samples) gangliosides measured by Mass Spectrometry
Timepoint [2] 302664 0
Visit 3 (14 days post baseline visit)
T0 (Baseline)

T2 (60 minutes post consumption of low/ high ganglioside milk drink)

T4 (240 minutes post consumption of low/ high ganglioside milk drink)
Secondary outcome [1] 336125 0
Saliva gangliosides measured by Mass Spectrometry
Timepoint [1] 336125 0
Visit 3 (14 days post baseline visit)
T0 (Baseline)

T2 (60 minutes post consumption of low/ high ganglioside milk drink)

T4 (240 minutes post consumption of low/ high ganglioside milk drink)

Eligibility
Key inclusion criteria
• Healthy females aged 18 – 40 years
• BMI 18.5 – 30 kg/m2
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Known history or presence of chronic disease – cancer, type 2 diabetes, heart disease, gastrointestinal disease, renal or hepatic disease, pancreatic insufficiency, stomach ulcers, drug abuse or alcoholism, thyroid disorders or any condition that may, in the opinion of the principle investigator, influence the study outcomes
• Any medical procedures deemed by the principal investigator to affect study outcomes
• Known food allergies, hypersensitivity, dietary avoidance or intolerance to the study foods
• Taking medications known to influence lipid metabolism, glucose tolerance and gastric emptying (oral contraceptives are accepted)
• Sufferer of bleeding disorders
• Self-reported pregnancy or breastfeeding
• Persons considered by the investigator to be unwilling, unlikely or unable to comprehend or comply with the study protocol.
• Participation in another research study within 30 days preceding the start of this study

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)
The allocation schedule will be determined by a staff member not involved in entering participants into the trial.

The schedule will remain concealed from those staff members study ID assignment is completed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Bio-availability
Statistical methods / analysis
Sample size is based on detecting statistical significant differences between the high and low ganglioside meals. Using G*Power 3.1.9.2 it was calculated that a sample size of 30 participants per group (60 in total) will provide 80% power (a 0.05, two-tailed, SD = 5.4 mg/L based on data from maternal serum concentrations to detect a significant difference between groups of 4 mg/L in serum ganglioside concentrations. Previous studies (Ma et al, 2015) have detected a difference of >5 mg/L between serums collected at the second and third trimesters of pregnancy, hence this difference is physiologically possible. The sample size calculated allows for a 10% withdrawal of participants without compromising statistical power.

Reference
Ma L, MacGibbon AKH, Mohamed H, Loy S, Rowan A, McJarrow P, Fong BY. Determination of ganglioside concentrations in breast milk and serum from Malaysian mothers using a high performance liquid chromatography-mass spectrometry-multiple reaction monitoring method. International Dairy Journal 2015;49:62-71.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/07/2017
Actual
Date of last participant enrolment
Anticipated
30/09/2017
Actual
Date of last data collection
Anticipated
31/10/2017
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 296603 0
Commercial sector/Industry
Name [1] 296603 0
Fonterra Co-operative Group
Country [1] 296603 0
New Zealand
Primary sponsor type
Government body
Name
CSIRO
Address
CSIRO
South Australian Medical Research Institute Building
North Terrace, Adelaide SA 5000
Country
New Zealand
Secondary sponsor category [1] 295752 0
None
Name [1] 295752 0
None
Address [1] 295752 0
None
Country [1] 295752 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297832 0
CSIRO Health and Medical Human Research Ethics Committee
Ethics committee address [1] 297832 0
PO Box 10041
Adelaide SA 5000
Ethics committee country [1] 297832 0
Australia
Date submitted for ethics approval [1] 297832 0
19/04/2017
Approval date [1] 297832 0
14/06/2017
Ethics approval number [1] 297832 0

Summary
Brief summary
Gangliosides are compounds of fat and carbohydrate (glycolipids) that are an important component in cell membranes of most animals and humans. They are found particularly abundant in the plasma membrane of the brain and central nervous system and are recognised as having an important role in their development. Gangliosides occur naturally in our diet and are high in foods from animal origin such as dairy products, meats and eggs. Gangliosides are particularly high in human breast milk. Enhanced cognitive development in infants is seen as an area of particular interest with previous research demonstrating that feeding infants from age 2-8 weeks until 24 weeks of age with an infant formula enriched in gangliosides was associated with improved cognitive development and increased blood levels of gangliosides at the 24 week time point, relative to normal formula fed controls.

The ultimate long-term goal is to optimise infant formula to replicate breast milk as closely as possible in both composition and impact on development. However, key information gaps exist regarding the bioavailability and absorption of bovine milk derived gangliosides from the gut and their impact on circulating levels of gangliosides. Addressing these gaps is the primary aim of this study.

Furthermore, the validation of a finger prick dried blood spot method may provide a long lived viable alternative to venepuncture-derived blood as a vehicle for quantifying total ganglioside levels in blood samples. In parallel with finger prick blood sampling, saliva samples will be collected from participants to identify if gangliosides are a measurable entity in this fluid, derived in a minimally invasive manner.
This study aims to:
1. Understand normal diurnal and day-to-day variation in ganglioside levels in healthy women of child bearing age
2. Describe the kinetics of uptake of bovine gangliosides after consuming a ganglioside-rich meal
3. Validate a finger prick dried blood spot method for measuring blood gangliosides (minimally invasive technique compared to venepuncture derived blood). Collect saliva samples in parallel with finger prick blood samples as a further minimally invasive measure of gangliosides.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75218 0
Dr Nathan O'Callaghan
Address 75218 0
CSIRO
South Australian Medical Research Institute Building
North Terrace, Adelaide SA 5000
PO Box 10041, Adelaide BC SA 5000, Australia
Country 75218 0
Australia
Phone 75218 0
+61 8 8303 8867
Fax 75218 0
Email 75218 0
Nathan.OCallaghan@csiro.au
Contact person for public queries
Name 75219 0
Nathan O'Callaghan
Address 75219 0
CSIRO
South Australian Medical Research Institute Building
North Terrace, Adelaide SA 5000
PO Box 10041, Adelaide BC SA 5000, Australia
Country 75219 0
Australia
Phone 75219 0
+61 8 8303 8867
Fax 75219 0
Email 75219 0
Nathan.OCallaghan@csiro.au
Contact person for scientific queries
Name 75220 0
Nathan OCallaghan
Address 75220 0
CSIRO
South Australian Medical Research Institute Building
North Terrace, Adelaide SA 5000
PO Box 10041, Adelaide BC SA 5000, Australia
Country 75220 0
Australia
Phone 75220 0
+61 8 8303 8867
Fax 75220 0
Email 75220 0
Nathan.OCallaghan@csiro.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23532Study protocol   
23533Informed consent form   
23534Clinical study report   
23535Ethical approval   

Results publications and other study-related documents

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

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4668Study results articleYes Stonehouse, W.; Klingner, B.; McJarrow, P.; Fong, ... [More Details] 373040-(Uploaded-21-09-2020-14-19-30)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseExploring in vivo dynamics of bovine milk derived gangliosides.2020https://dx.doi.org/10.3390/nu12030711
N.B. These documents automatically identified may not have been verified by the study sponsor.