Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000011482p
Ethics application status
Submitted, not yet approved
Date submitted
27/11/2024
Date registered
9/01/2025
Date last updated
9/01/2025
Date data sharing statement initially provided
9/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating protein supplementation in ulcerative colitis (SUPP-UC)
Scientific title
Evaluating the impact of protein supplementation of maintenance of remission in adults with quiescent ulcerative colitis
Secondary ID [1] 313475 0
None
Universal Trial Number (UTN)
U1111-1316-2235
Trial acronym
SUPP-UC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ulcerative colitis 335884 0
Condition category
Condition code
Oral and Gastrointestinal 332470 332470 0 0
Inflammatory bowel disease
Diet and Nutrition 332614 332614 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a double-blind, randomised, placebo-controlled supplementation study. The intervention and placebo will be provided to participants in the form of "supplement sachets" which will be developed in a commercial kitchen. The intervention sachet will contain 30g of whey protein isolate and 20g of full cream milk powder. Participants will consume three supplement sachets per day. Supplement sachets will be packaged in opaque black or white packaging to maintain blinding to the participants and study team. Only a research dietitian not involved in dietary education or data collection will be unblinded to which colour is allocated to the intervention and placebo. Participants will consume 3 supplement sachets per day for 24-weeks. Participants will receive a face-to-face 30-minute dietary education by a research dietitian at baseline to educate them on how they can incorporate the supplement sachets into their habitual diet. Participants will be educated on what foods from their usual diet they can replace with the supplement sachets to assist with maintaining an isocaloric intake. Participants will also be educated on eating to appetite. Education will be consistent across study arms to maintain consistency given the research dietitian will not know what supplement sachet participants are receiving. Participants will receive a supplement shaker cup and a supplementation guide as part of their dietary education. The supplementation guide will provide different ideas of how the sachets can be incorporated into different foods or fluids. Adherence will be assessed via self-reported questionnaire indicating number of non-adherent days and confirmed by participants returning their supplement packaging.
Intervention code [1] 330049 0
Treatment: Other
Comparator / control treatment
The placebo sachet will contain only the 20g of full cream milk powder. Therefore, this sachet acts as the placebo by the absence of the intervention product. Supplement sachets will be packaged in opaque black or white packaging to maintain blinding to the participants and study team. Only a research dietitian not involved in dietary education or data collection will be unblinded to which colour is allocated to the intervention and placebo. Participants will consume 3 supplement sachets per day for 24-weeks. Participants will receive a face-to-face 30-minute dietary education by a research dietitian at baseline to educate them on how they can incorporate the supplement sachets into their habitual diet. Participants will be educated on what foods from their usual diet they can replace with the supplement sachets to assist with maintaining an isocaloric intake. Participants will also be educated on eating to appetite. Education will be consistent across study arms to maintain consistency given the research dietitian will not know what supplement sachet participants are receiving. Participants will receive a supplement shaker cup and a supplementation guide as part of their dietary education. The supplementation guide will provide different ideas of how the sachets can be incorporated into different foods or fluids. Adherence will be assessed via self-reported questionnaire indicating number of non-adherent days and confirmed by participants returning their supplement packaging.
Control group
Placebo

Outcomes
Primary outcome [1] 340009 0
Maintenance of remission: defined as a simple clinical disease activity score (SCCAI) within 2 points of baseline score and/or no medical escalation of therapy between weeks 0 and 24 (measure as a composite outcome).
Timepoint [1] 340009 0
Baseline, and end of the following weeks post commencement of supplementation: end of week 4 post, end of week 8, end of week 12, end of week 16, end of week 20, end of week 24 (primary time point unless withdraws early).
Secondary outcome [1] 442293 0
Time (measured in days) to disease relapse and study withdrawal (assessed as a composite outcome): disease relapse and therefore withdrawal is defined as participants who have an increase in SCCAI of 2 or more points from baseline and/or escalation of medical therapy.
Timepoint [1] 442293 0
assessed at time of disease relapse/withdrawal for a maximum of 24 weeks post commencement of supplementation
Secondary outcome [2] 442297 0
A change in transmural disease activity between 0 and 24 weeks.
Timepoint [2] 442297 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [3] 442302 0
Incidence and severity of rectal bleeding between 0 and 24 weeks measured as a composite measure
Timepoint [3] 442302 0
Baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 8, end of week 12, end of week 16, end of week 20, end of week 24
Secondary outcome [4] 442305 0
An absolute change in biomarker of inflammation (faecal calprotectin) between 0 and 24 weeks.
Timepoint [4] 442305 0
Baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24
Secondary outcome [5] 442306 0
A mean/median change in quality of life between weeks 0 and 24.
Timepoint [5] 442306 0
Baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24
Secondary outcome [6] 442307 0
A mean/median change in food related quality of life between weeks 0 and 24.
Timepoint [6] 442307 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [7] 442308 0
A mean/median change in functional gastrointestinal symptoms between 0 and 24 weeks.
Timepoint [7] 442308 0
Baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 8, end of week 12, end of week 16, end of week 20, end of week 24
Secondary outcome [8] 442309 0
A mean/median change in bowel habit between 0 and 24 weeks
Timepoint [8] 442309 0
Baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 8, end of week 12, end of week 16, end of week 20, end of week 24
Secondary outcome [9] 442310 0
An absolute change in biochemistry (renal function) between 0 and 24 weeks.
Timepoint [9] 442310 0
Baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24
Secondary outcome [10] 442311 0
Safety via record of any adverse events between 0 and 24 weeks.
Timepoint [10] 442311 0
End of the following weeks post commencement of supplementation: end of week 4, end of week 8, end of week 12, end of week 16, end of week 20, end of week 24
Secondary outcome [11] 442312 0
Safety/tolerability of supplement sachets between 0 and 24 weeks.
Timepoint [11] 442312 0
End of the following weeks post commencement of supplementation: end of week 4, end of week 8, end of week 12, end of week 16, end of week 20, end of week 24
Secondary outcome [12] 442315 0
A change in metabolomics between 0 and 24 weeks.
Timepoint [12] 442315 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [13] 442316 0
A change in colonic microbial composition between 0 and 24 weeks
Timepoint [13] 442316 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [14] 442317 0
A change in colonic microbial diversity between 0 and 24 weeks
Timepoint [14] 442317 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [15] 442318 0
A change in colonic microbial functional potential between 0 and 24 weeks
Timepoint [15] 442318 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [16] 442319 0
A change in the proteome of biological samples between 0 and 24 weeks as a composite outcome
Timepoint [16] 442319 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [17] 442320 0
A mean/median change in weight between 0 and 24 weeks
Timepoint [17] 442320 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [18] 442321 0
A mean/median change in waist circumference between 0 and 24 weeks
Timepoint [18] 442321 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [19] 442322 0
A mean/median change in waist to hip ratio between 0 and 24 weeks.
Timepoint [19] 442322 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [20] 442323 0
Proportion change in hand grip strength between 0 and 24 weeks.
Timepoint [20] 442323 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [21] 442324 0
Proportion change in bilateral anterior thigh thickness between 0 and 24 weeks.
Timepoint [21] 442324 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24
Secondary outcome [22] 442325 0
Change in the proportion of fat mass and fat free mass between 0 and 24 weeks.
Timepoint [22] 442325 0
Baseline and end of the following weeks post commencement of supplementation: end of week 12, end of week 24 (optional for participants to participate in this)
Secondary outcome [23] 442326 0
Adherence to supplementation sachets between 0 and 24 weeks.
Timepoint [23] 442326 0
End of the following weeks post commencement of supplementation: end of week 2, end of week 4, end of week 6, end of week 8, end of week 10, end of week 12, end of week 14, end of week 16, end of week 18, end of week 20, end of week 22, end of week 24
Secondary outcome [24] 442327 0
Maintenance of habitual diet between 0 and 24 weeks
Timepoint [24] 442327 0
baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24
Secondary outcome [25] 442328 0
Tolerability/acceptability of supplement sachets between 0 and 24 weeks.
Timepoint [25] 442328 0
end of the following weeks post commencement of supplementation: end of week 4, end of week 8, end of week 12, end of week 16, end of week 20, end of week 24
Secondary outcome [26] 442860 0
Incidence and severity of rectal bleeding between 0 and 24 weeks measured as a composite measure
Timepoint [26] 442860 0
Baseline and post commencement of supplementation at the end of the following weeks: end of week 4, end of week 8, end of week 12, end of week 16, end of week 20k end of week 24
Secondary outcome [27] 442861 0
An absolute change in biomarker of inflammation (c-reactive protein) between 0 and 24 weeks.
Timepoint [27] 442861 0
baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24
Secondary outcome [28] 442862 0
An absolute change in biochemistry (liver function) between 0 and 24 weeks.
Timepoint [28] 442862 0
baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24
Secondary outcome [29] 442891 0
Nutritional adequacy of habitual diet between 0 and 24 weeks
Timepoint [29] 442891 0
baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24
Secondary outcome [30] 442892 0
Diet quality between 0 and 24 weeks
Timepoint [30] 442892 0
baseline and end of the following weeks post commencement of supplementation: end of week 4, end of week 12, end of week 24

Eligibility
Key inclusion criteria
- Adults aged 18 years or older
- Formal diagnosis of UC
- Stable on therapy for defined periods:
---> 4 weeks if no therapies
---> 4 weeks for oral and/or topical Aminosalicylates (5-ASA’s)
---> 8 weeks for immunomodulatory therapy
---> greater than or equal to 8 weeks anti-TNF (tumour necrosing factor)/ Ustekinumab/small molecule therapy
---> greater than or equal to 12 weeks vedolizumab
---> greater than or equal to 4 weeks after cessation of corticosteroids (prednisalone or budesonide)
---> greater than or equal to 4 weeks of stable dosing of prednisalone (less than or equal to 20mg) if steroid refractory
- Clinical disease activity score: Patient reported outcome (PRO2) score of less than or equal to 1 (where sub-score for rectal bleeding is equal to 0 and sub-score for stool frequency is equal to 1)
- A faecal calprotectin level of less than or equal to 250µg/g.
- Able to provide informed consent
- Willing to consume animal protein-based supplement sachets
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Aged < 18 years old
- Pregnant or breastfeeding
- Formal diagnosis of Crohn’s disease or Inflammatory Bowel Disease-Undetermined
- Chronic liver or kidney disease
- Enrolled in another clinical trial
- Unable to provide informed consent
- Cow’s milk protein allergy, soy allergy or lactose intolerance
- Vegan or ovo-vegetarian (does not consume animal by-products)
- Reliant on enteral and/or parenteral nutrition for provision of nutrition
- Prior colonic surgery
- Washout periods required for:
---> no protein supplementation in the past 2 weeks before trial commencement.
---> no antibiotic or corticosteroid use for any infection of other medical reason (except inclusion criteria above for corticosteroids) within the past 4 weeks prior to trial commencement
---> Diagnosis of COVID-19 infection within the past 4 weeks prior to trial commencement
---> No medications that alter bowel habit within the past 3 weeks of trial commencement (laxatives, opioids, anti-emetics, probiotics, anti-diarrhoeal)

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)
Allocation concealment - eligibility for the trial is determined at a seperate timepoint to allocation. Once a participant is enrolled and baseline assessments complete, the lead researcher will use REDCap computer software to randomly generate which colour opaque sachet the participant will receive in this trial. The lead researcher will not know which colour opaque sachet is allocated to the placebo and intervention throughout the entirety of the study.
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
Safety/efficacy
Statistical methods / analysis
A previous supplementation study investigating maintenance of remission was used to inform this power calculation. A two-sample t-test was used to calculate the sample size required to detect a difference between the intervention and placebo group. There is 80% power using alpha= 0.05 and standard deviation in SCCAI of 1.46 to detect a difference of 3-points between groups with n= 20 participants. To allow for 10% drop out, a sample of n=24 (n=12 in each group) is required.
Statistical analysis will follow an intention-to-treat analysis where last recorded values will be carried forward where a protocol breach/withdrawal may occur. Appropriate statistical tests will be used to compare endpoints between intervention and placebo groups including independent samples t-test or Mann Whitney-U test for continuous variables. Comparison of end points within groups (week 0 and week 24) will be performed using paired samples t-test or Kruskal Wallis test for continuous variables and chi-square tests or ANOVA for categorical variables. An interim analysis will occur after completion of 12 participants.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2025
Actual
Date of last participant enrolment
Anticipated
1/05/2026
Actual
Date of last data collection
Anticipated
2/11/2026
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 317915 0
Hospital
Name [1] 317915 0
The Queen Elizabeth Hospital
Country [1] 317915 0
Australia
Funding source category [2] 317916 0
Charities/Societies/Foundations
Name [2] 317916 0
European Crohn's Colitis Organisation Grant
Country [2] 317916 0
Austria
Primary sponsor type
Hospital
Name
The Queen Elizabeth Hospital, Central Adelaide Local health Network
Address
Country
Australia
Secondary sponsor category [1] 320261 0
None
Name [1] 320261 0
Address [1] 320261 0
Country [1] 320261 0
Other collaborator category [1] 283305 0
University
Name [1] 283305 0
The University of Adelaide
Address [1] 283305 0
Country [1] 283305 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316601 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 316601 0
Ethics committee country [1] 316601 0
Australia
Date submitted for ethics approval [1] 316601 0
22/11/2024
Approval date [1] 316601 0
Ethics approval number [1] 316601 0

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

Contacts
Principal investigator
Name 138378 0
Dr Alice Day
Address 138378 0
The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South SA 5011
Country 138378 0
Australia
Phone 138378 0
+61 478267780
Fax 138378 0
Email 138378 0
[email protected]
Contact person for public queries
Name 138379 0
Ms Rachel Davis
Address 138379 0
The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South SA 5011
Country 138379 0
Australia
Phone 138379 0
+61 432941868
Fax 138379 0
Email 138379 0
[email protected]
Contact person for scientific queries
Name 138380 0
Ms Rachel Davis
Address 138380 0
The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South SA 5011
Country 138380 0
Australia
Phone 138380 0
+61 478267780
Fax 138380 0
Email 138380 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.