ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12613001378718

Ethics application status

Approved

Date submitted

5/12/2013

Date registered

16/12/2013

Date last updated

10/05/2023

Date data sharing statement initially provided

10/05/2023

Date results provided

10/05/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

The Effect of a Multi-strain Probiotic on Metabolic Biomarkers in Adults with Pre-diabetes and Recently Diagnosed with Type 2 Diabetes

Scientific title

The Effect of a Multi-strain Probiotic on Metabolic Biomarkers in Adults with Pre-diabetes and Recently Diagnosed with Type 2 Diabetes

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Obesity

Insulin resistance

Type 2 Diabetes

Condition category

Condition code

Metabolic and Endocrine

Metabolic disorders

Alternative and Complementary Medicine

Other alternative and complementary medicine

Diet and Nutrition

Obesity

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Participants will be randomised to take either a multi-strain probiotic preparation or a placebo for 12 weeks duration and will be provided with supplementation every 6 weeks.
The product contains 8 probiotic strains (3 Lactobacillus, 3 Bifidobacterium, Streptococcus thermophilus and 1 yeast (500 mg per capsule equating to 50 billion cfu). Two capsules of the probiotic/placebo will be prescribed to be taken twice a day. The probiotic has to be consumed orally with cold non-carbonated water. The product should not be taken with hot and carbonated drinks.
Participants must return the remaining study supplement and a diary provided to record trial supplement intake every 6 weeks.

Intervention code [1]

Treatment: Other

Comparator / control treatment

The control group will take a placebo which contains inactive ingredients that will look, smell and taste like the probiotic but without any medical benefit. Participants randomised to the control group will take 2 capsules of the placebo preparation (200 mg of microcrytalline cellulose and excipients) twice a day for 12 weeks.

Control group

Placebo

Outcomes

Primary outcome [1]

Fasting plasma glucose

Timepoint [1]

Baseline and 12 weeks after intervention commencement

Secondary outcome [1]

Serum endotoxin quantified by the chromogenic Limulus amebocyte lysate assay

Timepoint [1]

Baseline and 12 weeks after intervention commencement

Secondary outcome [2]

Faecal microbial profiles (16S rRNA gene sequences)

Timepoint [2]

Baseline and 12 weeks after intervention commencement

Secondary outcome [3]

Faecal metabolomics profiles (SCFA, bile acids and choline will be assessed by GC-MS.

Timepoint [3]

Baseline and 12 weeks after intervention commencement

Secondary outcome [4]

Gut permeability (serum zonulin analysed by using the Human Haptoglobin Elisa kit)

Timepoint [4]

Baseline and 12 weeks after intervention commencement

Secondary outcome [5]

Physical activity measured by the Stanford Leisure-Time Activity Categorical Item (L-cat)

Timepoint [5]

Baseline, 6 weeks and 12 weeks after intervention commencement

Secondary outcome [6]

Triglycerides, cholesterol, LDL-cholesterol, HDL cholesterol and hs-CRP will be assessed by serum assays. Plasma free fatty acids will be measured using a quatification kit.

Timepoint [6]

Baseline and 12 weeks after intervention commencement

Secondary outcome [7]

Diet changes will be assessed by a 7-day food diary

Timepoint [7]

Baseline, 6 weeks and 12 weeks after intervention commencement

Secondary outcome [8]

Gastrointestinal Symptoms Rating Scale

Timepoint [8]

Baseline, 6 weeks and 12 weeks after intervention commencement

Secondary outcome [9]

HbA1c determined by HPLC

Timepoint [9]

Baseline and 12 weeks after intervention commencement

Secondary outcome [10]

Insulin resistance using HOMA and the insulin sensitivity index of matsuda

Timepoint [10]

Baseline and 12 weeks after intervention commencement

Eligibility

Key inclusion criteria

- Overweight adults (BMI greater than or equal to 25 kg/m2) with pre-diabetes (impaired fasting glucose, IFG and/or impaired glucose tolerance, IGT) or recently diagnosed with T2DM (less than 12 months)

- Treated by diet alone or diet plus metformin

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- Subjects with type 1 diabetes.
- Taking oral blood glucose-lowering medications or anti-obesity drugs (other than metformin)
Pregnant, breast feeding or planning on becoming pregnant
- Concomitant GI disorders.
- Taking antibiotics and dietary supplements including fish oil, probiotics, prebiotics, multivitamins, minerals, herbal preparations etc. 4 weeks before commencing the trial and for the duration of the trial.
- Alcohol abuse and the use of any illicit drug
- Any psychiatric disorders by history or examination that would prevent completion of the study or result in possible adverse events for the participant

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 will be provided by a holder of the allocation schedule who is off site from the study location.

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

Participants will be screened using the Boden Institute's database and by advertisements through the University of Sydney.

Potential participants will be invited to phone or email their interest to the clinical trial co-ordinator who will assess their initial eligibility. If eligible, potential participants will be asked to attend the Charles Perkins Centre at the University of Sydney to have an oral glucose tolerance test (prediabetics) or fasting glucose (T2DM). If the participants have IFG or/and IGT or T2DM for less than 1 year and meets all other eligibility criteria they will be invited to enrol in the study.

Participants and study investigators will be blinded to treatment allocation. The study coordinator will perform randomization though a computer randomization tool. As recruitment progresses, participants will be allocated to a treatment group that will be provided to the study investigator on a per-participant basis.

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

Phase 1

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Sample size:
From a clinical trial assessing the efficacy of a probiotic in adults with pre-diabetes (Heiman et al., unpublished data) we calculated the effect size using the outcome measure of blood glucose levels during a 2-hour OGTT. With a one-sided alpha set at 0.05 and power set at 0.85, the estimated sample size calculated using two-sample means test based upon Satterthwaite’s t-test is approximately 24 participants per group. Assuming a drop-out rate of 25%, the sample size should be inflated to 30 per group for a total sample size of 60.

Data analysis:
All data will be summarized descriptively using n, mean, median, standard deviation and 95% confidence intervals for continuous data, and frequency and percent for categorical data. Comparisons between the proportion of patients with IFG, IGT and T2DM will be made using Chi-square tests. Between group comparisons of glucose levels, triglycerides, free fatty acids, total cholesterol, HDL-c, LDL-c, zonulin, endotoxin, hs-CRP, BP, waist to hip ratio, and BMI will be conducted using ANOVA, with sex and baseline levels as covariates. Changes in gastrointestinal symptoms, quality of life and physical activity will be assessed according to the GSRS, SF-12v2 and IPAQ scoring manuals, respectively.

No adjustment for multiple comparisons will be made. All tests will be conducted two-sided and p values of less than 0.05 will be considered statistically significant.

Data will be analysed on an intent-to-treat basis using STATA MP v13 for Mac.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

23/03/2015

Actual

10/08/2015

Date of last participant enrolment

Anticipated

Actual

15/07/2016

Date of last data collection

Anticipated

Actual

19/10/2016

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]

2006 - The University Of Sydney

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Medlab Clinical Ltd

Address [1]

66 MacCauley Street, Alexandria NSW 2015

Country [1]

Australia

Primary sponsor type

University

Name

The University of Sydney

Address

Building D17, The University of Sydney, Camperdown NSW 2006

Country

Australia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District Human Reserach Committee

Ethics committee address [1]

Level 8, Building 14, Royal Prince Alfred Hospital, Camperdown NSW 2015

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

19/01/2015

Approval date [1]

22/04/2015

Ethics approval number [1]

X14-0369 & HREC/14/RPAH/492

Summary

Brief summary

The aim of this study is to assess the efficacy of a probiotic preparation in improving glucose metabolism and metabolic markers in adults with pre-diabetes and recently diagnosed with T2DM. Moreover, gut permeability, faecal and metabolomic profiles will be measured to evaluate a potential mechanisms of action of the multi-strain probiotic. We hypothesize that the administration of an evidence based probiotic preparation may modulate the GI microbiota from a dysbiotic to a balanced state improving blood glucose levels, decreasing inflammatory markers and endotoxaemia, and improving lipid profiles.

Trial website

Trial related presentations / publications

Palacios T, Coulson S, Butt H, Vitetta L. The effect of microbiota-based interventions and metformin in metabolic and inflammatory biomarkers in adults with type 2 diabetes mellitus. The Science of Nutrition in Medicine, 4rd International Conference. Gold Coast, Australia, 2-4 May, 2014.

Public notes

Contacts

Principal investigator

Name

Prof Ian Caterson

Address

Level 2 W80, Charles Perkins Centre D17, The University of Sydney, NSW, 2006

Country

Australia

Phone

+61 2 8627 1944

Fax

ian.caterson@sydney.edu.au

Contact person for public queries

Name

Talia Palacios

Address

Level 2 W80, Charles Perkins Centre D17, The University of Sydney, NSW, 2006

Country

Australia

Phone

+61 2 8627 1962

Fax

+61 2 8627 0141

talia.palacios@sydney.edu.au

Contact person for scientific queries

Name

Luis Vitetta

Address

66 McCauley St, Alexandria NSW 2015

Country

Australia

Phone

+61 4 0226 3316

Fax

luis.vitetta@sydney.edu.au

Data sharing statement

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

Yes

What data in particular will be shared?

IPD underlying published results only

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

From 1st July 2023 data will be available for an indefinite time

Available to whom?

Researchers from not-for-profit organisations. All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.

Available for what types of analyses?

Any approved protocol/proposal

How or where can data be obtained?

As of 1st July 2023, access can be requested via the Health Data Australia catalogue (https://www.researchdata.edu.au/health). Search for the ACTRN number in the catalogue to find datasets associated with this trial.

What supporting documents are/will be available?

Type	Citation	Link	Email	Other Details	Attachment
Study protocol	Palacios T, Vitetta L, Coulson S, Madigan CD, Denyer GS, Caterson ID. The effect of a novel probiotic on metabolic biomarkers in adults with prediabetes and recently diagnosed type 2 diabetes mellitus: study protocol for a randomized controlled trial. Trials. 2017 Jan 9;18(1):7. doi: 10.1186/s13063-016-1762-x. PMID: 28069054; PMCID: PMC5223589.	https://pubmed.ncbi.nlm.nih.gov/28069054/

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Palacios, T.; Vitetta, L.; Coulson, S.; Madigan, C... [More Details]	365393-(Uploaded-08-05-2023-10-36-19)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The effect of a novel probiotic on metabolic biomarkers in adults with prediabetes and recently diagnosed type 2 diabetes mellitus: Study protocol for a randomized controlled trial.	2017	https://dx.doi.org/10.1186/s13063-016-1762-x
Embase	Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?.	2018	https://dx.doi.org/10.1007/s11892-018-1057-6
Embase	Targeting the intestinal microbiota to prevent type 2 diabetes and enhance the effect of metformin on glycaemia: A randomised controlled pilot study.	2020	https://dx.doi.org/10.3390/nu12072041

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

Trial Review

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Documents added manually

Documents added automatically