ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618001391268

Ethics application status

Approved

Date submitted

14/08/2018

Date registered

20/08/2018

Date last updated

23/04/2020

Date data sharing statement initially provided

23/04/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

Specialised Fibre Supplement in Type 1 Diabetes

Scientific title

The safety, feasability and tolerability of a high amylose maize starch modified by acetylation and butyrylation in adults with type 1 diabetes.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type 1 diabetes

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This trial is a single arm, safety, tolerability and feasibility trial of a fibre supplement in adults with type 1 diabetes. The supplement is a high-amylose maize starch modified by acetylation and butyrylation. The supplement will be administered to adult participants at a dose of 40g/day for 6 weeks. The dose will be divided in two daily 20g doses, taken at a similar time each day, and combined with warmed or cold food of their choice (e.g. sauces, soups, yoghurt).
To improve tolerability, participants will start at 25% of the total dose (i.e. 10g/day) and increase the dose in 10g increments every 2 days. If the increased dose is not tolerated, the participant will remain on the previous dose for an additional 2 days before attempting the increased dose again. If that dose is not tolerated after the third attempt, they will remain on the previous dose for the remainder of the intervention. Adherence to the intervention will be assessed through the supplement dose logbook and supplements returned in the following visit.

Intervention code [1]

Treatment: Other

Comparator / control treatment

No control

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Feasibility of the study design. Feasibility will be assessed through recruitment and retention, compliance, withdrawal rate and data completion and accuracy. Recruitment and retention measures involve assessing the recruitment levels against target, withdrawal rates, timing and reasons as well as identifying barriers and opportunities in recruitment and retention. Compliance will be assessed through assessing unused supplement returned, proportion of doses recorded as consumed in the dose logbook and faecal short chain fatty acid measurements.

Timepoint [1]

Recorded 3, 6, and 12 weeks after supplement administration

Primary outcome [2]

Safety of the fibre supplement in the study population. Safety will be assessed through measuring toxicity, glycaemic control and incidence of adverse events. This will be measured through pathology of blood and urine, glycaemic control through the use of continuous glucose monitoring and side effects monitored through a validated 18 item, 5-point likert scale questionnaire to report any symptoms experienced since the previous visit with an additional 10 items included to capture diabetes-specific side effects. They will also be contacted by phone where notes and questionnaire responses will be recorded after 1 week of supplement administration.
For any serious adverse event or adverse reaction reported or detected will be reported immediately to the sponsor and the HREC which will be followed by a detailed written report and the participants may withdraw from the project at any time without affecting their relationship or usual clinical care.

Timepoint [2]

Recorded at baseline before supplement administration and 1, 3 and 6 weeks after supplement administration.

Primary outcome [3]

Tolerability of the supplement in the study population. This will be monitored through dose tolerability checked through gastrointestinal symptoms experienced (validated 18-item, 5-point likert scale questionnaire) and participant feedback (5-point likert scale questionnaire to record the acceptability and palatability of the supplement).

Timepoint [3]

At baseline before supplement consumption and 3 and 6 weeks after supplement consumption commencement.

Secondary outcome [1]

The effect of the specialised fibre supplement on plasma C-peptide, as an indicator of beta-cell function. It will be measured through a Mixed Meal Tolerance Test (MMTT). Plasma C-Peptide 2 hour area under the curve will be determined.

Timepoint [1]

C-Peptide will be measured at baseline before supplement consumption and at 6 and 12 weeks post supplement consumption commencement.

Secondary outcome [2]

The effect of the specialised fibre supplement on gut microbiome. Gut microbiome and proteome will be measured through stool samples which will be collected and analysed through DNA extraction for microbiome sequencing and faecal meta-proteomics, meta-genomic profiling to identify and quantify gut bacteria present and any shift in the community composition over time.

Timepoint [2]

At baseline before supplement consumption and 6 and 12 weeks after supplement consumption commencement.

Secondary outcome [3]

The effect of the specialised fibre supplement on changes in immune cell function. Immune cell phenotype will be measured through blood collection where mass flow cytometry analysis of immune cell phenotype will be performed to observe changes in ratio of regulatory to effector cell populations, antigen presenting cells etc.

Timepoint [3]

At baseline before supplement consumption and 6 and 12 weeks after supplement consumption commencement.

Secondary outcome [4]

The effect of the specialised fibre supplement on exogenous insulin requirements. Insulin will also be measured as the average total daily insulin dose with participant's usual record method (e.g. insulin pump downloads, smart blood glucose metres, smartphone application or paper-based logbooks).

Timepoint [4]

Insulin records will be collected at baseline before supplement consumption and 3, 6 and 12 weeks post supplement consumption commencement.

Eligibility

Key inclusion criteria

• 18 to 45 years, males and females
• Clinical diagnosis of T1D for at least 6 months
• HbA1c less than or equal to 8.5%
• Willing and able to follow study protocol
• stable disease management

Minimum age

18 Years

Maximum age

45 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Current or planned pregnancy or lactation during the study
• Use of diabetes medications other than insulin that affect glucose homeostasis
• Hypoglycaemia unawareness
• Concomitant disease or treatment that may, in the judgment of the investigators, impact on glycaemic control, insulin requirements or other outcome measures
• History or symptoms of gastrointestinal disease or malabsorption, including coeliac disease
• Any known condition that could be associated with poor compliance (e.g. drug/alcohol abuse)
• Weight below 50kg and above 120kg (to ensure full dose between 0.33- 0.80g/kg/day)
• Known liver or renal disease
• Use of senor-augmented insulin therapy (i.e. Medtronic 640G pump with low glucose suspend)
• Unwillingness to maintain their normal stable diet during the study and/or following a restrictive diet that would impact their ability to take the supplement (e.g. intermittent fasting).
• Recent antibiotic usage (previous 6 weeks) or anticipated antibiotic usage during the study.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety

Statistical methods / analysis

This trial is a pilot study and therefore not designed to be sufficiently powered to assess changes in exploratory outcome measures.
We will use a Proof-of-Concept dual-criteria approach for assessing endpoints of feasibility and safety.
When reporting data, comparison will be made on an intention to treat (ITT) basis. Discrete variables will be summarized by frequencies and percentages. Continuous variables will be summarized by use of standard measures of central tendency and dispersion (mean and standard deviation and/or quantile points). Outcome variables will be summarized over time. Binary outcomes will be summarized by n and percentages with chisq tests performed if appropriate. Where necessary outcome variables with a skewed distribution will be log-transformed to achieve normality and relative change (%) used to express change from baseline. A 5% significance level will be used (unadjusted for multiple comparisons). All comparisons will be two sided.
For multi-omic datasets, univariate and supervised and unsupervised multivariate analyses will be performed to identify proteins, genes and taxa with the most predictive power to discriminate any effects of the supplement. Data visualization, cross-validation, permutation tests, and correlation analysis will be performed to further assess the significance and relationship between the proteins, genes and taxa identified. Pathway and network analyses will seek to identify metabolic pathways that may be altered in the dataset using gene enrichment analysis, KEGG orthologues, and assigning bacterial modules and hierarchies using the bioinformatics tools GOmixer and MetaCyc. Using integrative multivariate approaches, we will identify combinations of biological features which are associated with phenotype using the statistical mixOmics package in ‘R’. Potential confounders including BMI, age and sex will also be examined.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

4/09/2018

Actual

25/09/2018

Date of last participant enrolment

Anticipated

1/02/2019

Actual

21/02/2019

Date of last data collection

Anticipated

29/04/2019

Actual

31/05/2019

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment postcode(s) [1]

2050 - Camperdown

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Juvenile Diabetes Research Foundation (JDRF) Australia

Address [1]

4/80-84 Chandos St
St Leonards NSW 2065

Country [1]

Australia

Primary sponsor type

University

Name

Monash University

Address

Scenic Blvd & Wellington Road
Clayton VIC 3800

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District Ethics Review Committee (RPAH Zone) [EC00113]

Ethics committee address [1]

Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

11/06/2018

Approval date [1]

02/07/2018

Ethics approval number [1]

Protocol No. X18-0166

Summary

Brief summary

Previous studies have shown specialized dietary fibre supplements can prevent type 1 diabetes in mice by altering the gut bacteria, reducing inflammation around the body and preventing the autoimmune destruction of the insulin-producing cells in the pancreas. While this fibre supplement has been used to treat other health conditions in humans, it has yet to be determined whether humans with type 1 diabetes will experience the same protection as mice. This pilot research trial therefore aims to determine whether a large clinical trial of this fibre supplement that releases high concentrations of the natural products, acetate and butyrate, is a) feasible, b) safe and c) well-tolerated in adults with established type 1 diabetes, and to (d) determine whether this supplement affects any markers of diabetes, such as changes in the gut microbiota and inflammatory markers, which would indicate the supplement would have a similar effect on type 1 diabetes protection in humans as in mice.
To achieve these aims, we will conduct a pilot study in 25 adults with pre-existing type 1 diabetes consuming the dietary fibre supplement twice daily for 6 weeks, with a follow-up at 12 weeks.  The supplement is an ordourless, tasteless powder that dissolves easily in cold or hot foods.  Eligible participants will attend the study centre on 4 separate occasions (baseline, 3, 6 and 12 weeks) and will receive dietary counselling and an individualised plan for the times of day they take the supplement and the specific foods in their usual diet they incorporate it into.  Participants will be monitored closely for changes in their blood, urine and stool pathology, their blood glucose control, insulin requirements, and any side effects or feedback on the supplement. Blood and stool samples will also be taken to at each visit to assess the preliminary efficacy of the dietary supplement and ensure the laboratory experiments are feasible for a future large clinical trial.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Eliana Marino Moreno

Address

Monash University
15 Innovation Walk, 75
Melbourne VIC, 3168

Country

Australia

Phone

+61 3 9902 4946

Fax

Eliana.Marino@monash.edu

Contact person for public queries

Name

Kirstine Bell

Address

Charles Perkins Centre (D17)
John Hopkins Dr
University of Sydney NSW 2006

Country

Australia

Phone

+61 2 8627 4250

Fax

Kirstine.Bell@sydney.edu.au

Contact person for scientific queries

Name

Eliana Marino Moreno

Address

Monash University
15 Innovation Walk, 75
Melbourne VIC, 3168

Country

Australia

Phone

+61 3 9902 4946

Fax

Eliana.Marino@monash.edu

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Deidentified participant data underlying published results

When will data be available (start and end dates)?

Following peer-reviewed publication (Start date to be determined). No end date determined.

Available to whom?

Case-by-case basis at the discretion of the Chief Investigators

Available for what types of analyses?

Analyses decided on a case-by-case basis at the discretion of the Chief Investigators

How or where can data be obtained?

Access subject to approvals by Chief Investigators (Contact Person: Kirstine.Bell@sydney.edu.au)

What supporting documents are/will be available?

Doc. No.	Type	Email
7742	Study protocol	Kirstine.bell@sydney.edu.au
7743	Informed consent form	Kirstine.bell@sydney.edu.au
7744	Ethical approval	Kirstine.bell@sydney.edu.au

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Novel Strategies to Protect and Visualize Pancreatic ß Cells in Diabetes	2020	https://doi.org/10.1016/j.tem.2020.10.002
Embase	Dietary SCFAs Immunotherapy: Reshaping the Gut Microbiota in Diabetes.	2021	https://dx.doi.org/10.1007/5584_2020_515
Embase	SCFAs in T1D: A microbiota-targeted approach for immune tolerance.	2022	https://dx.doi.org/10.1016/j.coemr.2022.100355

N.B. These documents automatically identified may not have been verified by the study sponsor.

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