Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001161718
Ethics application status
Approved
Date submitted
21/08/2022
Date registered
24/08/2022
Date last updated
13/06/2023
Date data sharing statement initially provided
24/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effects of cow, goat or sheep milk on nutrition and digestive comfort in older women
Scientific title
Effects of ruminant milk on nutrition and digestive comfort in older women: a randomised, controlled trial
Secondary ID [1] 307349 0
Nil known
Universal Trial Number (UTN)
U1111-1278-0857
Trial acronym
YUMMI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age-related gastrointestinal discomfort 326988 0
Condition category
Condition code
Diet and Nutrition 323883 323883 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 324517 324517 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will consist of two servings of cow, goat, or sheep milk powder per day for 12 weeks (40 people in each group). The milk powder will be made up with water to mimic the nutritional content of fresh milk: 40 g cow milk powder with 160 mL water; 35 g sheep milk powder with 215 mL water; 30 g goat milk powder with 200 mL water. The drinks will be consumed with breakfast and lunch.
The study duration is a nominal total of 14 weeks, with a 2-week lead-in phase and 12-week intervention phase.
During the 2-week lead-in phase (and throughout the duration of the intervention), participants will record their bowel habits every day, on an app designed for this study, and will complete weekly questionnaires about their digestive symptoms, mood (anxiety, depression), and sleep quality using validated questionnaires.
On the 2nd week of the lead-in phase, participants will complete a non-consecutive 3-day diet, wear an actigraphy accelerometer for 7-days to measure activity levels, and undergo a Dual-energy X-ray Absorptiometry (DXA) scan to measure body composition. The day before their baseline visit, participants will collect a faecal sample, and will fast overnight for 9 hours.
At the baseline clinic (beginning of the intervention phase), participants will provide a blood sample, have height, weight and waist circumference measured, and undergo functional tests (hand grip strength and a walk test). They will also complete a set of questionnaires about their mental health.
At the clinic, a sub-group of participants from each milk group will consume double the amount of the milk powder that they have been assigned (80 g cow milk powder; 70 g sheep milk powder; 60 g goat milk powder). The powders will be made up to 350 mL with water. The participants will consume the milk within 10 minutes. After finishing the milk, they will provide blood samples hourly over 5-hours. During this time they will complete questionnaires on digestive comfort and appetite. This sub-group assessment will be undertaken once at baseline and again at follow-up (week 12). The double-amount of powder consumed during the clinic will replace the participant's regular intervention (two daily serves of milk powder with breakfast and lunch) for the first and last days of the intervention period. The first 25 people in each group who consent to participating in the sub study will be enrolled.
Participants will be given four weeks supply of milk powder to take home. At weeks 4 and 8, participants will return any unused milk powder, and be provided with their next 4-week supply. Compliance will be monitored by checklist, and by weighing left-over milk powder. Participants will also have their waist circumference and body weight measured at the clinics.
At the final follow-up visit, participants will repeat all of the aforementioned baseline visit procedures. The week prior to their follow-up visit, they will complete the same set of questionnaires, 3-day diet record, actigraphy, DXA scan, and collect a faecal sample. At the follow-up clinic visit, they will have their weight and waist circumference measured, and provide a fasted blood sample. The participants in the sub study will provide blood samples before and hourly, up to 5 hours, after consuming their milk. All participants will receive their reimbursement ($200 grocery voucher). Attendance of clinic visits and completion of questionnaires and study tests (accelerometery, DXA, functional tests, blood tests) will be assessed to measure the adherence of participants.
Intervention code [1] 323874 0
Treatment: Other
Comparator / control treatment
The control group will undertake all study measurements, and will follow their usual diet with no restrictions on milk or dairy intake.
Control group
Active

Outcomes
Primary outcome [1] 332352 0
Changes in abdominal pain scores from the Gastrointestinal Symptom Rating Scale (GSRS).

The GSRS is a validated instrument with a 1-week recall that assesses symptom severity using a 7-grade Likert scale, ranging from 1 (“no discomfort at all”) to 7 (“very severe discomfort”).
Timepoint [1] 332352 0
Measured weekly for the duration of the study (from 2 weeks prior to intervention commencement to 12 weeks post-intervention commencement).
Primary outcome [2] 332353 0
Changes in bowel comfort scores from the Gastrointestinal Symptom Rating Scale (GSRS).
Timepoint [2] 332353 0
Measured weekly for the duration of the study (from 2 weeks prior to intervention commencement to 12 weeks post-intervention commencement).
Primary outcome [3] 332354 0
Changes in protein intake, using 3-day diet records.
Timepoint [3] 332354 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).
Secondary outcome [1] 413145 0
Changes in blood selenium, zinc, and magnesium levels.
Timepoint [1] 413145 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).
Secondary outcome [2] 413146 0
Determine habitual food and nutrient intake (protein, total fat, calcium, magnesium) before and during the intervention using a three-day food diary.
Timepoint [2] 413146 0
Baseline (end of 2nd week of lead-in phase) and during the final week of the intervention (12 weeks post-intervention commencement).
Secondary outcome [3] 413147 0
Changes in depression scores using the validated Patient-Reported Outcomes Measurement Information System Questionnaire (PROMIS Depression).
Timepoint [3] 413147 0
Measured weekly for the duration of the study (from 2 weeks prior to intervention commencement to 12 weeks post-intervention commencement).
Secondary outcome [4] 413148 0
Changes in anxiety scores using the validated Patient-Reported Outcomes Measurement Information System Questionnaire (PROMIS Anxiety).
Timepoint [4] 413148 0
Measured weekly for the duration of the study (from 2 weeks prior to intervention commencement to 12 weeks post-intervention commencement).
Secondary outcome [5] 413149 0
Changes in fat-free body mass as measured with Dual-energy X-ray Absorptiometry (DXA).
Timepoint [5] 413149 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).
Secondary outcome [6] 413150 0
Changes in physical activity levels as measured with accelerometry for seven days at the start and end of the intervention.
Timepoint [6] 413150 0
Baseline (end of 2nd week of lead-in phase) and during the last week of the intervention (12 weeks post-intervention commencement).
Secondary outcome [7] 413151 0
Changes in handgrip strength as measured with a dynamometer.
Timepoint [7] 413151 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).
Secondary outcome [8] 413152 0
Changes in the faecal metabolome, metagenome (DNAseq), metagenome assemblies, bile and organic acid production assessed as a composite outcome from faecal sample.
Timepoint [8] 413152 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).
Secondary outcome [9] 413153 0
Changes in plasma metabolome and neurotransmitters assessed as an exploratory composite outcome from plasma samples.
Timepoint [9] 413153 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).
Secondary outcome [10] 413154 0
Changes in stool form, frequency, and comfort, assessed as a composite outcome, using a bowel habit diary (mobile phone app).
Timepoint [10] 413154 0
Measured daily for the duration of the study (from 2 weeks prior to intervention commencement to 12 weeks post-intervention commencement).
Secondary outcome [11] 413155 0
Changes in the composite cardiovascular risk profile measure by lipid profile assessed using a blood sample, height using a stadiometer, weight using weighing scales, waist circumference using measuring tape and blood pressure using electronic blood pressure (BP) apparatus.
Timepoint [11] 413155 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).
Secondary outcome [12] 413156 0
Postprandial plasma leucine area under the curve (AUC).
This analysis will be conducted on the first 25 participants in each group who consent to the sub study.
Timepoint [12] 413156 0
This measurement will be undertaken at baseline and at the end of the intervention (12 weeks post-intervention commencement).
Plasma amino acids will be measured before commencement of drinking milk to ascertain fasting amino acid concentrations.
Postprandial measurements will be taken at 60, 120, 180, 240, and 300 minutes after consuming the milk.
Secondary outcome [13] 413157 0
Postprandial satiety, as measured by a visual analogue hunger scale and calculated as areas under the curve.
This analysis will be conducted on the first 25 participants in each group who consent to the sub study.
Timepoint [13] 413157 0
This measurement will be undertaken at baseline and at the end of the intervention (12 weeks post-intervention commencement).
The hunger scale satiety values will be collected at the following time intervals: fasting, and 60, 120, 180, 240, and 300 minutes after consumption of the milk.
Secondary outcome [14] 413158 0
Comparison of the GlucoTRIG index scores between the different milks, as an exploratory analysis.

The GlucTRIG index measures blood insulin and triglyceride responses after ingesting a food, to rank the foods according to nutritional quality and carbiometabolic risk.

Reference: Thota, R.N., Moughan, P.J., Singh, H. et al. GlucoTRIG: a novel tool to determine the nutritional quality of foods and meals in general population. Lipids Health Dis 19, 83 (2020). https://doi.org/10.1186/s12944-020-01268-w
Timepoint [14] 413158 0
This measurement will be undertaken at baseline and at the end of the intervention (12 weeks post-intervention commencement), and will be performed on the first 25 participants in each group who consent to the sub study..
Plasma insulin and triglycerides will be measured before commencement of drinking the milk to ascertain fasting values.
A postprandial measurement will be taken at 180 minutes after consumption of the milk.
Secondary outcome [15] 413262 0
Postprandial plasma amino acids under the curve (AUC), as an exploratory analysis.
This analysis will be conducted on the first 25 participants in each group who consent to the sub study.
Timepoint [15] 413262 0
This measurement will be undertaken at baseline and at the end of the intervention (12 weeks post-intervention commencement).
Plasma amino acids will be measured before commencement of drinking milk to ascertain fasting amino acid concentrations.
Postprandial measurements will be taken at 60, 120, 180, 240, and 300 minutes after consuming the milk.
Secondary outcome [16] 413263 0
Postprandial gastrointestinal (GI) comfort, as measured by a visual GI comfort scale and calculated as areas under the curve.
This analysis will be conducted on the first 25 participants in each group who consent to the sub study.
Timepoint [16] 413263 0
This measurement will be undertaken at baseline and at the end of the intervention (12 weeks post-intervention commencement).
The hunger scale satiety values will be collected at the following time intervals: fasting, and 60, 120, 180, 240, and 300 minutes after consumption of the milk.
Secondary outcome [17] 413264 0
Changes in sleep quality using the validated Leeds Sleep Questionnaire.
Timepoint [17] 413264 0
Measured weekly for the duration of the study (from 2 weeks prior to intervention commencement to 12 weeks post-intervention commencement).
Secondary outcome [18] 413265 0
Changes in walking speed as measured with the Timed Walk Test.
Timepoint [18] 413265 0
Baseline (end of 2nd week of lead-in phase) and at the end of the intervention (12 weeks post-intervention commencement).

Eligibility
Key inclusion criteria
Women who live independently and are free from serious medical illness such as cancer, uncontrolled diabetes or cardiovascular disease, with a Body Mass Index between 18.5 to 30 kg/m2, and do not undertake more than 2 hours of structured exercise each day.
Minimum age
60 Years
Maximum age
80 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
•Inability to give informed consent
•Taken antibiotics within the month before starting the study
•Use of certain prescribed medication or recreational drugs within the last three months that could affect the gastrointestinal tract: opioids, non-steroidal anti-inflammatory drugs, proton pump inhibitors, laxatives, prebiotic or probiotic supplements.
•Medical history of gastrointestinal surgery or disorders (inflammatory bowel disease, ulcerative colitis, coeliac disease, Crohn's disease), cardiorespiratory problems, uncontrolled diabetes mellitus, bleeding disorders, sleep disorders, psychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, post-traumatic stress disorder)
•Alarm features associated with significant gastrointestinal or other disorders, such as burning pain in the epigastrium which increases during the night and wakes up the patient; frequent vomiting; loss of appetite; lower gastrointestinal bleeding; odynophagia; dysphagia; palpable abdominal mass; lymphadenopathy; jaundice.
•Significant dietary changes within the month before starting the trial (i.e., being on a controlled diet or dietary weight loss regimen)
•Dairy intolerance of, or ruminant milk allergy
•High habitual milk intake (> 500 mL per day on average)
•Malnutrition Screening Tool (MST) score of 2 or more points
•Cigarette smoking or other use of tobacco or nicotine-containing products
•Excessive alcohol intake >20g of pure alcohol (2 drinks)/d on average (>21 standard drinks a week)
•Inability or unwillingness to comply with the study procedures

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 of the participants will be undertaken using sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation will be concealed with a pre-specified computer-generated random block randomisation list prepared by the study statistician. Participants will be randomised 1:1:1:1 into either one of the milk groups or into the control group.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample size of 34 women per group will detect a difference of 0.7 within the constipation pain domain of the GSRS at week-12 between each intervention and the control group, with 5% significance and 80% power. This sample size will also detect a difference in mean nutrient intake (protein, fat, calcium, magnesium), between each milk group compared with control group assuming effect sizes of 0.5. The sample is increased to 40 participants per group to allow for uncertainty of the estimates and attrition.
For the sub-study analyses, sample size of 25 will to detect differences in plasma leucine appearance (AUC) at 60 minutes post-ingestion between ovine and bovine milk.

Presenting features and all outcomes measures with be summarised using standard descriptive statistics including means, medians, standard deviations and ranges and frequencies and percentages depending on the variable types. Outcomes as levels and changes will be compared between groups using general linear models or non-parametric approaches for continuous measures and chi-square tests and logistic regressions for categorical variables. Analyses will explore pairwise comparisons amongst the groups. All analyses will be undertaken using SPSS v27 and a two-tailed p-value <0.05 will be taken to indicate statistical significance.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/01/2023
Actual
20/03/2023
Date of last participant enrolment
Anticipated
31/07/2023
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
160
Accrual to date
38
Final
Recruitment outside Australia
Country [1] 24964 0
New Zealand
State/province [1] 24964 0
Dunedin

Funding & Sponsors
Funding source category [1] 311635 0
Government body
Name [1] 311635 0
Ministry of Business Innovation and Employment
Country [1] 311635 0
New Zealand
Funding source category [2] 312089 0
Commercial sector/Industry
Name [2] 312089 0
NIG Nutritionals Ltd
Country [2] 312089 0
New Zealand
Primary sponsor type
University
Name
Riddet Institute
Address
Massey University Manawatu (Turitea)
Tennet Drive
Palmerston North 4474

Private Bag 11 222
Palmerston North 4442
Country
New Zealand
Secondary sponsor category [1] 313072 0
University
Name [1] 313072 0
University of Otago
Address [1] 313072 0
PO Box 56
Dunedin 9054
Country [1] 313072 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311092 0
University of Otago Human Ethics Committee (Health)
Ethics committee address [1] 311092 0
Ethics committee country [1] 311092 0
New Zealand
Date submitted for ethics approval [1] 311092 0
09/05/2022
Approval date [1] 311092 0
07/06/2022
Ethics approval number [1] 311092 0
H22/067

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

Contacts
Principal investigator
Name 119914 0
Dr Jody Miller
Address 119914 0
University of Otago,
Department of Human Nutrition
PO Box 56
Dunedin 9054
Country 119914 0
New Zealand
Phone 119914 0
+64 4 4797559
Fax 119914 0
Email 119914 0
[email protected]
Contact person for public queries
Name 119915 0
Holly Abbotts-Holmes
Address 119915 0
University of Otago,
Department of Human Nutrition
PO Box 56
Dunedin 9054
Country 119915 0
New Zealand
Phone 119915 0
+64 021 2790140
Fax 119915 0
Email 119915 0
[email protected]
Contact person for scientific queries
Name 119916 0
Jody Miller
Address 119916 0
University of Otago,
Department of Human Nutrition
PO Box 56
Dunedin 9054
Country 119916 0
New Zealand
Phone 119916 0
+64 4 4797559
Fax 119916 0
Email 119916 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
Individual data is not available to the public. It would be a breach of data security.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16981Informed consent form  [email protected]



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.