Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001209987
Ethics application status
Approved
Date submitted
15/10/2020
Date registered
13/11/2020
Date last updated
1/09/2024
Date data sharing statement initially provided
13/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Dose Determination and Efficacy Evaluation of the Gastrointestinal ReProgramming (GaRP) Dietary supplement in Irritable Bowel Syndrome patients
Scientific title
Dose Determination and Efficacy Evaluation of the Gastrointestinal ReProgramming (GaRP) Dietary supplement in IBS patients: A Randomized, Double-blind, Placebo-controlled clinical trial
Secondary ID [1] 302540 0
ANR-GARP-001
Universal Trial Number (UTN)
U1111-1259-5826
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Irritable Bowel Syndrome 319410 0
Condition category
Condition code
Oral and Gastrointestinal 317382 317382 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Dosed with oral GaRP equivalent to 240 mg of bromelain twice a day for 8 weeks
Arm 2: Dosed with oral GaRP equivalent to 480 mg of bromelain twice a day for 8 weeks.

Participants will record the time of dosage in their electronic diaries. All unused product will be returned at the completion of the trial for reconciliation.
Intervention code [1] 318826 0
Treatment: Drugs
Comparator / control treatment
Arm 3 : Dosed with oral matching placebo twice a day for 8 weeks
The placebo will be comprised of microcrystalline cellulose coated in the same enteric coating as the treatment
Control group
Placebo

Outcomes
Primary outcome [1] 325418 0
The number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0

The individual components are recognised as generally safe, however it is possible that adverse events could occur from the mixture of the components together. Some side effects of the components of this supplement in the literature include : flatulence, nausea/vomiting, diarrhoea, epigastric pain/heartburn, allergic rash, dizziness, obstipation (severe constipation), meteorism (swollen abdomen), headache, throat irritation/ oro-pharyngeal pain, dyspepsia, dry mouth, loss of appetite, increased thirst and increased urination
Timepoint [1] 325418 0
Baseline to EOT 8 weeks
Primary outcome [2] 325419 0
IBS-SSS scale scores as a continuous variable at Days 7, 14, 28, 42 and 56
Timepoint [2] 325419 0
baseline and 7, 14, 28, 42 and 56 days post baseline
Secondary outcome [1] 387886 0
Proportion of participants who achieve the following IBS-SSS scale scores Days 7, 14, 28, 42 and 56:
a) <75 points on the IBS-SSS scale
b)75-175 points on the IBS-SSS scale
c)175-225 points on the IBS-SSS scale
d)225 -300 points on the IBS-SSS scale
e)>300 points on the IBS-SSS scale
Timepoint [1] 387886 0
Days 7, 14, 28, 42 and 56: post baseline
Secondary outcome [2] 387887 0
Number of participants who achieve the following IBS-SSS scale scores :
o <75 points on the IBS-SSS scale
o 75-175 points on the IBS-SSS scale
o 175-225 points on the IBS-SSS scale
o 225 -300 points on the IBS-SSS scale
o >300 points on the IBS-SSS scale
Timepoint [2] 387887 0
Days 7, 14, 28, 42 and 56:
Secondary outcome [3] 387889 0
IBS Adequate Relief (IBS-AR) asking “In the last 7 days, have you had adequate relief of your IBS symptoms?” compared to baseline. A participant is considered a responder if they answer “yes”. Comparison using the difference between baseline and weekly measurements until Day 56 post commencement of intervention.
.
Timepoint [3] 387889 0
weekly for 8 weeks
Secondary outcome [4] 387890 0
Hospital Anxiety and Depression (HAD) Scale comparing to baseline.
Timepoint [4] 387890 0
Baseline, day 56
Secondary outcome [5] 387891 0
Safety markers - Serum Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), Gamma-glutamyl transpeptidase (GGT) and full blood count via blood test measured
Timepoint [5] 387891 0
Baseline, day 56,
Secondary outcome [6] 402187 0
Change in IBS-QoL score compared to baseline measured at days 14, 28, 42 and 56 post baseline.
Timepoint [6] 402187 0
days 14, 28, 42 and 56 post baseline

Eligibility
Key inclusion criteria
Patients who:
• Have irritable bowel syndrome with a moderate IBS-SSS score of 175-350 as assessed by the IBS-SSS questionnaire.
• Have IBS as defined by Rome IV
• recurrent abdominal pain on average at least 1 day/week in the last three months associated with two or more of the following:
o Related to defecation
o Associated with a change in frequency of stool
o Associated with a change in form of stool
• Have abdominal pain intensity where the weekly average of worst daily (in past 24 hours) abdominal pain score is > 30 on a 0 to 100-point scale at screening
• Agree not to make significant changes to their diet or exercise routines during the study.
• If a women of child-bearing potential, agrees to use an acceptable method of birth control (true abstinence, birth control pills, injections or contraceptive implants) while on treatment and following completion of 2 menstrual cycles or 2 months after the last dose of study treatment, and if male a barrier method of birth control from randomisation until the Follow- Up visit.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants who
•1. Have a body mass index of <18 or >39.9kg/m2.
2. Have a significant acute or chronic coexisting illness such as psychiatric*,
immunological or cardiovascular (not including controlled hypertension or
stable endocrine considerations) that contraindicates, in the investigator’s
judgement, entry to the study.
a) Participants who have ‘alarm symptoms’ (e.g., unexplained weight
loss family history of colon cancer or inflammatory bowel disease or
rectal bleeding) may be eligible if organic pathology is excluded by a
detailed work-up prior to enrolling the participant.
b) * Participants with a psychiatric illness particularly in the category of
chronic and non-psychotic, such as anxiety and /or depression, are
eligible provided the investigator deems involvement will not to
place the participant at risk and that the participant is considered
reliable.
3. Have confirmed clinical diagnosis of bile acid diarrhoea and/or are on
medication for bile acid diarrhoea.
4. Have IBS-C as defined by Rome IV Subtype Classification.
5. Currently have, or have a history of, inflammatory bowel disease (e.g.,
ulcerative colitis, Crohn’s disease), or have a faecal calprotectin level of >50
ug/g at enrolment or C-reactive protein level of >5.0mg/L.
6. Have diagnosed coeliac disease.
7. Have had previous abdominal surgery (excluding laparoscopic
cholecystectomy, appendectomy, hysterectomy, and hernia repair).
8. Have radiation proctitis or other known poorly controlled medical conditions
that could interfere with bowel function.
9. Have a malignant disease (other than localised skin cancers) or any
concomitant end-stage organ failure.
10. In the opinion of the investigator, are poor attendees or unlikely for any
reason to be able to comply with the study requirements.
11. Are currently, or in the past 30 days have been, enrolled in another
investigational device or drug study(s), or are currently receiving other
investigational agent(s).
12. Have used /weaned from long term systemic corticosteroids or antibiotics
within the past month prior to screening or have used short -term systemic
corticosteroids or antibiotics within the fourteen days prior to screening.
13. Are taking narcotics (e.g., tramadol, codeine, morphine).
14. Have changed their diet routine, e.g. FODMAP, gluten-free, within the past
month.
15. Are taking probiotics.
16. Have chronic drug therapy that interferes with vitamin D metabolism, such
as glucocorticoids, or have a chronic disease such as renal failure, liver
disease, epilepsy or diabetes mellitus (except for possibly stable type 2
diabetes where the medical management has been unchanged for >6
months on a case-by-case basis in discussion with Principal Investigator, and
only on the basis it is deemed not to put the participant at a higher risk of
experiencing adverse reaction and/or interfere with the integrity of study
outcomes) .
17. Have experienced a cardiovascular event such as congestive heart failure,
heart attack, stroke, or angina (chest pain) in the past 3 months.
18. Require concomitant treatment with any prohibited medication. In
accordance with Section 8.9, a participant may be permitted to enter the
study if they have been on a stable dose for at least 3 months prior to
Screening. The Principal Investigator has the discretion to make a definitive
call on a case-by-case basis if it is deemed not to put the participant at a
higher risk of experiencing clinically significant adverse reaction and/or
interfere with the integrity of study outcomes.
19. Have planned investigational procedures while participating in this study
that would interfere with normal food intake or influence abdominal
symptoms.
20. Have known current infection with HIV, or hepatitis A, B, or C.
21. Have abnormal laboratory values at screening deemed by the investigator to
be clinically significant.
22. Have a known allergy to pineapple.
23. Are pregnant or breast feeding.

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
For each participant the study will last for 12 weeks; including 8 weeks of treatment, preceded by a 2-week screening/baseline period and followed by a 2-week washout period. Patients will also have the option continue with this washout period for an additional 6 weeks.
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The demographic data will be summarised by dose group. The continuous variables will be summarised as sample size, mean, standard deviation, minimum, median, and maximum. The categorical variables will be summarised as frequencies and percentages.

The interim analysis and final analysis comprise a group sequential test for efficacy and non-binding futility. IBS-SSS will be the efficacy variable of interest. At the interim analysis each dose group will be tested against the placebo group. The level of significance was set to 0.025 for the test of each dose group against placebo. Thus the overall level of significance was 0.05. IBS-SSS will be analysed over time with a mixed model for repeated measurements (MMRM) with baseline IBS-SSS as the covariate, and sequential multiple imputation to estimate the missing observations. The fixed effects will include: dose group, time, baseline covariate, and the interaction between dose group and time. The random effects shall be the participant. The variance-covariance structure will be selected based on AIC, and BIC. The assumptions of MMRM such as Normally distributed residuals will be assessed graphically. If necessary rectifying transformations will be applied. For each dose group the t-test for the interim analysis, and the final analysis will be calculated as a one-degree of freedom contrast at Day 56. The IBS-SSS with be displayed graphically over time as mean with 95% CI. The results in each treatment group will be combined to form an ‘all treated’ group which will be assessed in the same manner.

The continuous efficacy variables such as IBS-QoL will be analysed over time with a MMRM as described for IBS-SSS. For all secondary efficacy variables the level of significance will be 0.05 with no adjustment for multiplicity of tests.

The binary and categorical efficacy variables will be analysed respectively with logistic regression, or log-linear models. The log-likelihood ratio statistic, which is chi-square distributed, will be used to test the association between the dose group and the efficacy variable of interest.

Safety analyses will include summaries for adverse events, clinical laboratory tests, vital signs and physical exams. The continuous safety parameters will be summarised by dose group and time as: mean, standard deviation, minimum, median, maximum, and 95% CI; and change from baseline will be summarised similarly. Compliance and concomitant medications will also be summarized

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/10/2021
Actual
2/10/2021
Date of last participant enrolment
Anticipated
29/11/2024
Actual
Date of last data collection
Anticipated
31/01/2025
Actual
Sample size
Target
200
Accrual to date
61
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 306977 0
Commercial sector/Industry
Name [1] 306977 0
Anatara Lifesciences
Country [1] 306977 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Anatara Lifesciences
Address
C/- Perks, Level 8, 81 Flinders Street, Adelaide, SA, 5000 Australia
Country
Australia
Secondary sponsor category [1] 307539 0
None
Name [1] 307539 0
Address [1] 307539 0
Country [1] 307539 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307108 0
Bellberry
Ethics committee address [1] 307108 0
Ethics committee country [1] 307108 0
Australia
Date submitted for ethics approval [1] 307108 0
13/10/2020
Approval date [1] 307108 0
05/02/2021
Ethics approval number [1] 307108 0

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

Contacts
Principal investigator
Name 106062 0
Dr Joanne Grimsdale
Address 106062 0
56-56A Thompson Street, Drummoyne, NSW, 2047
Country 106062 0
Australia
Phone 106062 0
+61297193852
Fax 106062 0
Email 106062 0
[email protected]
Contact person for public queries
Name 106063 0
David Brookes
Address 106063 0
Anatara Lifesciences, C/- Perks, Level 8, 81 Flinders Street, Adelaide, SA, 5000 Australia
Country 106063 0
Australia
Phone 106063 0
+61 411712579
Fax 106063 0
Email 106063 0
[email protected]
Contact person for scientific queries
Name 106064 0
David Brookes
Address 106064 0
Anatara Lifesciences, C/- Perks, Level 8, 81 Flinders Street, Adelaide, SA, 5000 Australia
Country 106064 0
Australia
Phone 106064 0
+61 411712579
Fax 106064 0
Email 106064 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
No additional documents have been identified.