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Trial registered on ANZCTR


Registration number
ACTRN12623000630617
Ethics application status
Approved
Date submitted
25/05/2023
Date registered
8/06/2023
Date last updated
27/10/2023
Date data sharing statement initially provided
8/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The INHABIT (synergIstic effect of aNtHocyAnin and proBIoTics in) Inflammatory Bowel Disease Trial: A double-blind randomised controlled trial.
Scientific title
The INHABIT (synergIstic effect of aNtHocyAnin and proBIoTics in) Inflammatory Bowel Disease Trial: A double-blind randomised controlled trial assessing faecal calprotectin, gut microbiota profile and quality-of-life.
Secondary ID [1] 308171 0
None
Universal Trial Number (UTN)
Trial acronym
INHABIT (synergIstic effect of aNtHocyAnin and proBIoTics)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild-moderate Ulcerative Colitis 327889 0
Condition category
Condition code
Oral and Gastrointestinal 324976 324976 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A double-blind randomised controlled trial of 12 weeks duration with four intervention arms containing 25 participants in each: 1) 310mg anthocyanin derived from New Zealand Blackcurrants and placebo probiotic; 2) multi-strain probiotic and placebo fruit powder; 3) 310mg anthocyanin plus a multi-strain probiotic; 4) placebo fruit powder and placebo probiotic.

Anthocyanin intervention: 12g freeze-dried Blackcurrant powder will be consumed daily by participants in intervention arms 1 & 2. This provides 310mg anthocyanins/day. The product can be mixed in any cold, low acidity, non-carbonated drink or food (ie smoothie, juice, water, milk or on yoghurt or cereal).

Probiotic intervention: Participants in intervention arms 2 & 3 will receive a multi-strain probiotic, in the form of two daily sachets. This probiotic contains one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B breve BB02; B animalis subspecies [subsp] lactis BL03, previously identified as B longum BL03; and B animalis subsp lactis BI04, previously identified as B infantis BI04), and four strains of Lactobacilli (L acidophilus BA05, L plantarum BP06, L paracasei BP07, and L helveticus BD08, previously identified as L delbrueckii subsp bulgaricus BD08). This proprietary multi-strain probiotic (VSL#3) contains no less than 450 billion colony-forming units (CFU) per single sachet. The product can be mixed in any cold, low acidity, non-carbonated drink or food (ie smoothie, juice, water, milk or on yoghurt or cereal).

Participants will receive the interventions by the research team consisting of dietitians. Participants will be instructed to take the products daily for duration of the trial, with specific intake instructions provided during the first visit.

Participants will be required to retain product packaging and return at the final appointment as a measure of adherence.
Intervention code [1] 324629 0
Treatment: Other
Comparator / control treatment
Placebo: Participants in intervention arms 3 and 4 will receive 12g of a placebo powdered fruit extract with the same texture and taste as the anthocyanin powder. Participants in intervention arms 1 and 4 will receive two placebo sachets of similar appearance to the provided probiotic.
The placebo fruit powder is composed of citri fibre, citric acid, maltrin, caster sugar, tartaric acid, blackcurrant flavour, raspberry flavour and colouring agents.
The placebo probiotic powder is composed of maltose.
Control group
Placebo

Outcomes
Primary outcome [1] 332803 0
. Primary outcome is health-related quality-of-life measured through the Inflammatory Bowel Disease Questionnaire - 32 item (IBDQ32)
Timepoint [1] 332803 0
The IBDQ32 will be assessed at baseline, 6-weeks and 12-weeks post-intervention commencement.
The primary timepoint is baseline to 12-weeks post intervention commencement.
Secondary outcome [1] 414730 0
Shotgun metagenomic analysis of faecal microbiota
Timepoint [1] 414730 0
Baseline and 12-weeks post-intervention commencement.
Secondary outcome [2] 414734 0
Cognitive performance will be assessed using the Stroop test.
Timepoint [2] 414734 0
Baseline and 12-weeks post-intervention commencement.
Secondary outcome [3] 414735 0
Faecal calprotectin
Timepoint [3] 414735 0
Baseline and 12 weeks post-intervention commencement.
Secondary outcome [4] 414736 0
Stool consistency will be assessed using a self-assessed Bristol stool chart rating.
Timepoint [4] 414736 0
Baseline, 6 weeks and 12 weeks post-intervention commencement
Secondary outcome [5] 422523 0
Mood will be assessed as a composite outcome using the Depression, anxiety and stress scale 21 (DASS-21)
Timepoint [5] 422523 0
Baseline and 12-weeks post-intervention commencement
Secondary outcome [6] 422524 0
Verbal learning and memory will be assessed using the Rey Auditory Verbal Learning Test (RAVLT)
Timepoint [6] 422524 0
Baseline and 12-weeks post-intervention commencement.
Secondary outcome [7] 422525 0
Inflammatory Bowel Disease Symptom Inventory Short-form (IBDSI-SF)
Timepoint [7] 422525 0
Baseline, 6 weeks and 12 weeks post-intervention commencement
Secondary outcome [8] 428245 0
Simple Clinical Colitis Activity Index (SCCAI).
Timepoint [8] 428245 0
Secondary outcome [9] 428246 0
Simple Clinical Colitis Activity Index (SCCAI).
Timepoint [9] 428246 0
Baseline and 12-weeks post-intervention commencement.

Eligibility
Key inclusion criteria
1) diagnosis of Ulcerative Colitis for at least 3 months prior to screening, documented by endoscopic and histologic findings; 2) aged >/= 18 yrs; 3) willing and able to take oral supplements; 4) able to communicate in the English language.

As per the Medical Advisor’s recommendation, all participants must have stable medication for 2 weeks prior to commencing the study. All types of IBD medications are permitted in this study. Patients receiving topical therapy (enemas or suppositories) are eligible to participate if they are willing to continue the therapy at a stable dose throughout the study.
Participant receiving steroids >20mg/day can commence the study 2 weeks after their dosage has reduced to ?20mg/day. Participants treated with steroids ?20mg/day are eligible to participate if they plan to maintain this stable dose for all the study duration.

Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria: 1) Crohn’s Disease; 2) change in antibiotics or probiotics in past 3 months; 3) escalation to biologics or immunomodulators in the past 6 weeks; 4) currently taking steroids >20 mg daily; 5) bowel resection surgery; 6) pregnant and lactating women; 7) end-stage liver or kidney failure; 8) current treatment for C. difficile or other intestinal infections; 9) Sucrose-isomaltose deficiency or maltose intolerance.

Participants who require a change in their medication treatment related to uncontrolled UC activity (i.e. increase in steroids or mesalamine doses, start of steroids or biologics or immunosuppressants) during the 12-week intervention, those who do not comply with the study protocol, and those who voluntarily leave the study will not be included in the per-protocol analyses. These participants will be encouraged to continue to complete required outcome data and attend the final visit for inclusion in the intention-to-treat analysis.

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 participants to the intervention groups will be concealed from the principle research team who enroll participants. This person will not be involved with the research interface.

Randomisation of participants will be conducted by a staff member not involved in the participant interface.
Active and placebo products will be identically labelled with only batch number evident.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be block randomised upon enrolment in the trial, and information regarding randomisation will not be revealed to researchers until after data analysis.
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
This is a parallel four-arm clinical trial, testing the individual, synergistic (combined) and placebo effect of 2 supplements.

In the case that unblinding is required for medical reasons or adverse reactions throughout the trial, the staff member responsible for randomisation will reveal the product allocation to the participant.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
IBDQ-32, faecal calprotectin (FCAL) and gut microbiota taxonomy will be evaluated using repeated measures ANOVA and/or mixed linear modelling to evaluate changes due to the interventions. Covariates will be included in these analyses if necessary. Correlation and regression methods will be used to examine the relationships between measures, particularly between changes in FCAL and any significant changes on the gut microbiota.


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2023
Actual
Date of last participant enrolment
Anticipated
1/06/2024
Actual
Date of last data collection
Anticipated
1/09/2024
Actual
Sample size
Target
100
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment postcode(s) [1] 40452 0
2217 - Kogarah
Recruitment postcode(s) [2] 40453 0
2522 - University Of Wollongong

Funding & Sponsors
Funding source category [1] 312427 0
University
Name [1] 312427 0
University of Wollongong
Country [1] 312427 0
Australia
Funding source category [2] 312439 0
Commercial sector/Industry
Name [2] 312439 0
Actial Farmaceutica
Country [2] 312439 0
Italy
Funding source category [3] 312440 0
Commercial sector/Industry
Name [3] 312440 0
Arepa Holdings Limited
Country [3] 312440 0
New Zealand
Primary sponsor type
University
Name
University of Wollongong
Address
Northfields Avenue, Wollongong NSW 2522
Country
Australia
Secondary sponsor category [1] 314017 0
None
Name [1] 314017 0
None
Address [1] 314017 0
NA
Country [1] 314017 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311772 0
University of Wollongong Human Research Ethics Committee
Ethics committee address [1] 311772 0
Northfields Avenue, Wollongong NSW 2522
Ethics committee country [1] 311772 0
Australia
Date submitted for ethics approval [1] 311772 0
05/05/2023
Approval date [1] 311772 0
22/05/2023
Ethics approval number [1] 311772 0
2022/315

Summary
Brief summary
Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disease, affecting approximately 1 in 250 Australians. Ulcerative colitis is a sub-type of IBD. Scientific research exploring the effectiveness of nutritional therapies in adults with Ulcerative Colitis has not yet found many definitive conclusion, therefore more research is needed. In addition, research testing how these nutritional therapies change the gut microbiota may be beneficial at developing anti-inflammatory nutritional therapies that help to manage this burdensome disease.

There is a lack of clinical trials that have tested both changes to inflammatory markers and the gut microbiota in adults with inflammatory bowel disease, after taking a microbiota-modulating therapy. Plant athocyanins and probiotics have both been shown to reduce inflammation, however not enough to be effective in adults with IBD. In this study, we plan to test for the first time whether combining both an anthocyanin and a probiotic will result in more effective reductions in inflammation and therefore beneficial disease control.

This study aims to evaluate the effectiveness of a multi-strain probiotic intervention provided together with dietary anthocyanins extracted from the New Zealand Blackcurrants on the gut microbiota profile and inflammatory biomarkers in adults with mild-moderate Ulcerative Colitis.

We hypothesise that the combination of anthocyanins and probiotics will lead to reduction in gut inflammation in participants (measured through faecal calprotectin), and will alter the gut microbiota. We hypothesise that these improvements will be more significant in participants who take the combined intervention (anthocyanin + probiotic) rather than participants who take the anthocyanin alone or probiotic alone.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122314 0
A/Prof Kelly Lambert
Address 122314 0
University of Wollongong, Northfields Avenue, Wollongong NSW 2522
Country 122314 0
Australia
Phone 122314 0
+61 2 4221 5251
Fax 122314 0
Email 122314 0
[email protected]
Contact person for public queries
Name 122315 0
Denelle Cosier
Address 122315 0
University of Wollongong, Northfields Avenue, Wollongong NSW 2522
Country 122315 0
Australia
Phone 122315 0
+61 4 7711 2768
Fax 122315 0
Email 122315 0
[email protected]
Contact person for scientific queries
Name 122316 0
Denelle Cosier
Address 122316 0
University of Wollongong, Northfields Avenue, Wollongong NSW 2522
Country 122316 0
Australia
Phone 122316 0
+61 4 7711 2768
Fax 122316 0
Email 122316 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
SourceTitleYear of PublicationDOI
EmbaseThe INHABIT (synergIstic effect of aNtHocyAnin and proBIoTics in) Inflammatory Bowel Disease trial: A study protocol for a double-blind, randomised, controlled, multi-arm trial.2024https://dx.doi.org/10.1017/jns.2023.113
N.B. These documents automatically identified may not have been verified by the study sponsor.