Trial Review

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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 information initially 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] 283665 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 290619 0
Insulin resistance 290620 0
Type 2 Diabetes 294399 0
Condition category
Condition code
Metabolic and Endocrine 291010 291010 0 0
Metabolic disorders
Alternative and Complementary Medicine 291011 291011 0 0
Other alternative and complementary medicine
Diet and Nutrition 291120 291120 0 0
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] 288365 0
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] 290995 0
Fasting plasma glucose
Timepoint [1] 290995 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [1] 305763 0
Serum endotoxin quantified by the chromogenic Limulus amebocyte lysate assay
Timepoint [1] 305763 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [2] 305816 0
Faecal microbial profiles (16S rRNA gene sequences)
Timepoint [2] 305816 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [3] 305861 0
Faecal metabolomics profiles (SCFA, bile acids and choline will be assessed by GC-MS.
Timepoint [3] 305861 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [4] 306007 0
Gut permeability (serum zonulin analysed by using the Human Haptoglobin Elisa kit)
Timepoint [4] 306007 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [5] 306008 0
Physical activity measured by the Stanford Leisure-Time Activity Categorical Item (L-cat)
Timepoint [5] 306008 0
Baseline, 6 weeks and 12 weeks after intervention commencement
Secondary outcome [6] 313374 0
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] 313374 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [7] 313377 0
Diet changes will be assessed by a 7-day food diary
Timepoint [7] 313377 0
Baseline, 6 weeks and 12 weeks after intervention commencement
Secondary outcome [8] 313382 0
Gastrointestinal Symptoms Rating Scale
Timepoint [8] 313382 0
Baseline, 6 weeks and 12 weeks after intervention commencement
Secondary outcome [9] 324157 0
HbA1c determined by HPLC
Timepoint [9] 324157 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [10] 324158 0
Insulin resistance using HOMA and the insulin sensitivity index of matsuda
Timepoint [10] 324158 0
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?
No
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
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3536 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 9339 0
2006 - The University Of Sydney

Funding & Sponsors
Funding source category [1] 288365 0
Commercial sector/Industry
Name [1] 288365 0
Medlab Clinical Ltd
Country [1] 288365 0
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] 287085 0
None
Name [1] 287085 0
None
Address [1] 287085 0
None
Country [1] 287085 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292481 0
Sydney Local Health District Human Reserach Committee
Ethics committee address [1] 292481 0
Level 8, Building 14, Royal Prince Alfred Hospital, Camperdown NSW 2015
Ethics committee country [1] 292481 0
Australia
Date submitted for ethics approval [1] 292481 0
19/01/2015
Approval date [1] 292481 0
22/04/2015
Ethics approval number [1] 292481 0
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 44630 0
Prof Ian Caterson
Address 44630 0
Level 2 W80, Charles Perkins Centre D17, The University of Sydney, NSW, 2006
Country 44630 0
Australia
Phone 44630 0
+61 2 8627 1944
Fax 44630 0
Email 44630 0
ian.caterson@sydney.edu.au
Contact person for public queries
Name 44631 0
Mrs Talia Palacios
Address 44631 0
Level 2 W80, Charles Perkins Centre D17, The University of Sydney, NSW, 2006
Country 44631 0
Australia
Phone 44631 0
+61 2 8627 1962
Fax 44631 0
+61 2 8627 0141
Email 44631 0
talia.palacios@sydney.edu.au
Contact person for scientific queries
Name 44632 0
Prof Luis Vitetta
Address 44632 0
66 McCauley St, Alexandria NSW 2015
Country 44632 0
Australia
Phone 44632 0
+61 4 0226 3316
Fax 44632 0
Email 44632 0
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?

TypeCitationLinkEmailOther DetailsAttachment
Study protocolPalacios 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
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes 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
SourceTitleYear of PublicationDOI
EmbaseAltered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?.2018https://dx.doi.org/10.1007/s11892-018-1057-6
EmbaseThe 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.2017https://dx.doi.org/10.1186/s13063-016-1762-x
EmbaseTargeting the intestinal microbiota to prevent type 2 diabetes and enhance the effect of metformin on glycaemia: A randomised controlled pilot study.2020https://dx.doi.org/10.3390/nu12072041
N.B. These documents automatically identified may not have been verified by the study sponsor.