Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000484741
Ethics application status
Approved
Date submitted
16/03/2022
Date registered
28/03/2022
Date last updated
28/03/2022
Date data sharing statement initially provided
28/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The role of nutritional interventions in the fight against antimicrobial resistance
Scientific title
The effect of nutritional interventions on gut microbiome composition in adults previously treated with antibiotics
Secondary ID [1] 306640 0
INT001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Antimicrobial Resistance 325563 0
Acute infection treated with antibiotics 325564 0
Condition category
Condition code
Inflammatory and Immune System 322936 322936 0 0
Other inflammatory or immune system disorders
Infection 323073 323073 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
60 Participants (4 groups of n=15) will be provided with one of the following interventions to consume once daily for 8 weeks (56 ± 2 days). All products are commercially available.

Intervention (#1): A synbiotic (Caruso’s Once Daily Probiotics - as in the control) + peppermint oil (NOW Foods Peppermint Gels). Each capsule contains 0.4ml of peppermint oil.

Intervention (#2): A synbiotic (Caruso’s Once Daily Probiotics – as in the control) + micronutrient (Health Aid Multi Minerals)
Health Aid Multi Minerals – each tablet contain (average):
Vitamin D (400 iu): 10µg
Calcium: 163mg
Iron: 3.3mg
Zinc: 3mg
Iodine:58µg
Copper: 0.5mg
Manganese: 1.6mg
Chromium: 25µg
Molybdenum: 400µg
L-Glutamic Acid: 25mg
Betaine Hydrochloride: 25mg

Intervention (#3): A synbiotic (Caruso’s Once Daily Probiotics – as in the control) + polyphenol (California Gold Nutrition, Trans-Resveratrol)
California Gold Nutrition, Trans-Resveratrol- each tablet contains:
Trans-Resveratrol (as Veri-teTM 98% Trans-Resveratrol) 200mg

Other ingredients – modified cellulose, microcrystalline, rice extract and rice hull. These products are commercially available and can be purchased in supermarkets. For this study, these nutritional supplements will be supplied to the participants to consume for the duration of the study period.

All interventions will be consumed in the form of capsules/tablets. Adherence to the intervention will be monitored by a weekly email sent to the participant for them to complete and also a paper product checklist they will complete at home and bring to the final appointment. The participant will also return all packaging at their final visit.
Intervention code [1] 323079 0
Treatment: Other
Comparator / control treatment
Participants in each group (n=15) with the comparison from baseline to endpoint after 8 weeks of taking supplements.

Comparator: Probiotic + prebiotic (synbiotic): Caruso's Once Daily Probiotic - is a one-a-day probiotic supplement that provides a potent amount of 32 billion good bacteria plus a prebiotic fibre in each capsule.
Each capsule contains, 32 Billion CFU
Lactobacillus rhamnosus, 200 Million CFU
Lactobacillus plantarum, 14 Billion CFU
Lactobacillus casei, 7 Billion CFU
Lactobacillus salivarius, 6.6 Billion CFU
Lactobacillus acidophilus, 4 Billion CFU
Bifidobacterium lactis, 200 Million CFU
Inulin, 110mg
Control group
Active

Outcomes
Primary outcome [1] 330705 0
Change in gut microbiome composition using shotgun sequencing to provide species to strain level identification and functional genomics analysis of each bacterial species present in a faecal sample
Timepoint [1] 330705 0
Baseline and 8 weeks post-intervention commencement
Secondary outcome [1] 407260 0
Changes in gut permeability (leaky gut) through blood analysis. Blood sample taken after 90minutes after the consumption of the 100ml sugar drink containing (Lactulose 5g/rhamnose 1g) by a qualified nurse or phlebotomist
Timepoint [1] 407260 0
Baseline and 8 weeks post-intervention commencement
Secondary outcome [2] 407317 0
Changes in blood metabolomics and metagenomics, Immune markers - IL-1beta, IL-6, and TNF-alpha
Timepoint [2] 407317 0
Baseline and 8 weeks post-intervention commencement
Secondary outcome [3] 407318 0
Changes in Urine metabolomics and metagenomics, Metabolites will be analyzed using a liquid chromatography. Metagenomics will be quantified and qualified by a NanoDrop ND-1000 spectrophotometer.
Timepoint [3] 407318 0
Baseline and 8 weeks post-intervention commencement
Secondary outcome [4] 407319 0
Changes in faecal short chain fatty acids (SCFA) measured by gas chromatography
Timepoint [4] 407319 0
Baseline and 8 weeks post-intervention commencement
Secondary outcome [5] 407321 0
Changes in gastrointestinal symptoms measured by the Gastrointestingal Symptom Rating Scale (GSRS) survey
Timepoint [5] 407321 0
Baseline and 8 weeks post-intervention commencement
Secondary outcome [6] 407322 0
Immune markers in saliva using a custom 15-plex Cyto/Chemo panel on the Luminex 200.
Timepoint [6] 407322 0
Baseline and 8 weeks post-intervention commencement
Secondary outcome [7] 407338 0
Dietary Habitual Intake assessed using a digital food diary collected via a smartphone application Research Food Diary. 3 x 24 hour diet recalls completed on separate days within 7 days (two weekdays and one weekend day) after visit 1 (Baseline) and before visit 2 (8 weeks post-intervention commencement).
Timepoint [7] 407338 0
Baseline to 8 weeks post intervention commencement

Eligibility
Key inclusion criteria
1. Willing to provide written Informed Consent
2. Able to access own email inbox
3. Be able to attend the CSIRO nutrition clinic for around 2.5 hours on two occasions across an eight-week period.
4. Willing to consume their regular habitual diet throughout the study period
5. Adults (males and females)
6. =18-<66 years of age at clinic screen
7. BMI of =18.5 - =35 kg/m2
8. An episode of acute infection (any type) requiring at least one course of antibiotics in the past 3 months*
*Self-reported, no clinical testing will be performed
Minimum age
18 Years
Maximum age
66 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Health conditions* that could affect gut and immune health such as gastrointestinal diseases [including, but not limited to diverticulitis, ulcerative colitis, Crohn’s disease, or coeliac disease, colostomy], type 1 or type 2 diabetes, cancer, renal or liver diseases in the last 12 months.
2. Immunocompromised (diagnosed with HIV, AIDS) or having an organ or bone marrow transplant in the last 12 months.
3. Gastrointestinal symptoms* (i.e. pain, reflux, diarrhea, or constipation), surgeries* (i.e. bariatric surgery such as gastric banding) or use of medications* (i.e. appetite suppressants (orlistat, phentermine and liraglutide), steroids (corticosteroids, progestogen, androgens and estrogens) known to potentially affect energy intake, appetite, or gastrointestinal motor function
4. Have a biliary disorder
5. Currently taking medication for hypertension and or high cholesterol
6. Currently taking supplements (probiotics, prebiotics, fibre, micronutrients, multivitamins, essential oils) or functional foods (fermented food, polyphenols) in the previous 4 weeks of Visit 1.
7. Known food allergies or intolerances to the study intervention products
8. Pregnant and/or lactating women
9. Current smoker (or history of smoking within the last six months)
10. History of or known presence of alcohol abuse or illicit drug use*
11. Received an investigational drug within 28 days prior to Visit 1 that in the opinion of the investigator may affect the applicant’s ability to participate in the study or the study results
*Self-reported, no clinical testing will be performed

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)
Following Informed Consent and study eligibility confirmation, the participant will be randomised for the order in which they will receive the test products. Participants will be randomly assigned by computer sequence generation (http://www.randomisation.com) to one of four treatments. The random allocation sequence will be generated by the Clinic Manager who is not involved with entering participants into the trial to ensure allocation concealment.
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 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
A total of 60 participants will be recruited (n=15/group), allowing for a 25% dropout rate. Based on previous data and experiments a sample size of n=12-15 was sufficient to provide 80% power at a significance level of <0.05 to detect a difference in the gut microbiome alpha diversity and observed richness (beta diversity) profile before and after the administration of the nutritional interventions. Relative abundance, alpha and beta diversity of the microbiome will be analysed using a one-way ANOVA to compare across the different groups followed by a Bonferroni post-hoc to determine the significance between groups. Statistical significance will be set at a two-sided p-value of 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/04/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 37046 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 310965 0
Government body
Name [1] 310965 0
CSIRO
Country [1] 310965 0
Australia
Primary sponsor type
Government body
Name
CSIRO
Address
Gate 13, Kintore Avenue, Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 312289 0
None
Name [1] 312289 0
Address [1] 312289 0
Country [1] 312289 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310523 0
CSIRO Health and Medical Human Research Ethics Committee
Ethics committee address [1] 310523 0
Ethics committee country [1] 310523 0
Australia
Date submitted for ethics approval [1] 310523 0
08/12/2021
Approval date [1] 310523 0
15/02/2022
Ethics approval number [1] 310523 0
2021_108_HREC

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

Contacts
Principal investigator
Name 117950 0
Dr Cuong Tran
Address 117950 0
CSIRO, Gate 13, Kintore Avenue, Adelaide, SA, 5000
Country 117950 0
Australia
Phone 117950 0
+61 8 8303 8905
Fax 117950 0
+61 8 8303 8899
Email 117950 0
[email protected]
Contact person for public queries
Name 117951 0
Cuong Tran
Address 117951 0
CSIRO, Gate 13, Kintore Avenue, Adelaide, SA, 5000
Country 117951 0
Australia
Phone 117951 0
+61 8 8303 8905
Fax 117951 0
+61 8 8303 8899
Email 117951 0
[email protected]
Contact person for scientific queries
Name 117952 0
Cuong Tran
Address 117952 0
CSIRO, Gate 13, Kintore Avenue, Adelaide, SA, 5000
Country 117952 0
Australia
Phone 117952 0
+61 8 83038905
Fax 117952 0
+61 8 8303 8899
Email 117952 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
Group analysis. Raw line by line data will not be published.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15369Study protocol  [email protected]
15370Informed consent form  [email protected]
15371Ethical approval  [email protected]
15373Other  [email protected] Participant Information Sheet



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.