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Trial registered on ANZCTR


Registration number
ACTRN12615001135505
Ethics application status
Approved
Date submitted
3/09/2015
Date registered
27/10/2015
Date last updated
21/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of probiotics on glycaemic control in Type 2 diabetes mellitus patients
Scientific title
Gut Hormone and Anti-Inflammatory Pathways Underlying Probiotic-Effects on Glycaemic Control, Gut Microbiota and Quality of Life among Type 2 Diabetes Mellitus Patients: A Study Protocol
Secondary ID [1] 287280 0
NIL
Universal Trial Number (UTN)
U1111-1173-2147
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 295918 0
Condition category
Condition code
Metabolic and Endocrine 296170 296170 0 0
Diabetes
Alternative and Complementary Medicine 296813 296813 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be assigned randomly to receive a capsule of 10 billion CFU probiotic mixture twice daily (Probio-Tec Registered Trademark, Chr Hansen Holding A/S, Denmark) or placebo, for a duration of 24 weeks.

a) Composition of probiotic mixture: Bifidobacterium BB-12 Registered Trademark and
Lactobacillus rhamnosus LGG Registered Trademark (LGG Registered Trademark is a registered trademark of Valio Ltd.) (50%:50%)
b) dose of each microorganism: 1 billion CFU for each strain per capsule
c) mode of administration: oral capsule

Adherence assessment: Pill(capsule) counting, clinic appointment, phone interview and self-reported assessment
Intervention code [1] 292590 0
Treatment: Other
Comparator / control treatment
Patients in the placebo group will receive 2 capsules of placebo product, that is similar in appearance and composition but without any probiotics.

Composition of placebo: Maltodextrin, microcrystalline cellulose, magnesium stearate and silicon dioxide.
Control group
Placebo

Outcomes
Primary outcome [1] 295842 0
glycosylated hemoglobin (HbA1c)

Assess by: ELISA kit
Timepoint [1] 295842 0
At baseline, Week 12 and Week 24 follow up
Secondary outcome [1] 316710 0
Glycaemic parameters [fasting blood glucose (FBG), insulin)] Assess by: ELISA kits/ serum assay
Timepoint [1] 316710 0
At baseline, Week 12 and Week 24 follow up
Secondary outcome [2] 318365 0
Lipid profile (total cholesterol, HDL, LDL, TG)

Assess by: Serum assay (Will be done by hospital laboratory)
Timepoint [2] 318365 0
At baseline, week12, and week 24 follow up
Secondary outcome [3] 318366 0
Inflammatory markers [C-reactive protein, TNF-a, IL-6, IL-10]

Assess by: ELISA kit/serum assay
Timepoint [3] 318366 0
At baseline, week12, and week 24 follow up
Secondary outcome [4] 318367 0
Stress oxidative parameters [blood superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, catalase (CAT) activity, gluthathione (GSH), gluthatione reductase (GR), malondialdehyde (MDA)] Assess by: ELISA kits/serum assay
Timepoint [4] 318367 0
At baseline, week 12 and week 24 follow up
Secondary outcome [5] 318368 0
Anthropometric measurements (weight, height, BMI, waist circumference, hip circumference)

Assess by: Standard method of measuring (measurement tape and etc.)
Timepoint [5] 318368 0
At baseline, week 12 and week 24 follow up
Secondary outcome [6] 318370 0
Diabetes quality of life score Assess by: Validated Malaysian version of Diabetes Quality of Life-Brief Clinical Inventory (DQoL-BCI)
Timepoint [6] 318370 0
At baseline, week 12 and week 24 follow up
Secondary outcome [7] 338987 0
Gut Microbiota Profiling (Metagenomic Sequencing) Assess by: QIAamp DNA Stool Mini Kit and Genomic Sequencing
Timepoint [7] 338987 0
At baseline, Week 12 and Week 24 follow up
Secondary outcome [8] 338988 0
Gut hormone: glucagon-like peptide 1 (GLP-1). Assess by: ELISA kits/serum assay
Timepoint [8] 338988 0
At baseline, Week 12 and Week 24 follow up

Eligibility
Key inclusion criteria
1) T2DM patients, with glycosylated hemoglobin (HbA1c) of 7% to 10%
2) No change in oral hypoglycaemic agents during the last 3 months
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Already on insulin or insulin analogs or maximum dose of oral hypoglycaemic agents
2.Regular intake of probiotics (including fermented dairy products), antacids, H2-receptor blockers, proton pump inhibitors, loperamide, corticosteroids or sex steroids
3.Systemic antibiotics within 1 month before inclusion
4.Active smokers (still smoking at least 1 cigarette for the past 6 months)
5.Daily alcohol consumption >30 g
6.Significant immunodeficiency
7.Liver, thyroid, kidney or cardiac valvular disorder
8.Chronic gastrointestinal disease
9.Neurological disorders (e.g. Alzheimer's disease, stroke, Parkinson disease)
10.Breast-feeding, pregnancy or plan to become pregnant in the next 6-12 months
11.Participation in another clinical trial within the last 6 months
12.Enduring mental health problems (e.g. schizophrenia, bipolar disorder)
13.Incapacity to give consent

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)
All medical staff, nursing staff, dietician, researchers and patients will be blinded to the randomised allocation unless the sealed envelope identifying the intervention in the Study Pack

The randomisation process for the patients enrolled in the study will be conducted by an independent researcher, who is not involved in this study. Randomisation will be conducted using a computer program and the codes will remain in the Faculty of Pharmacy, UiTM until study completion.
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
All collected data will be analysed using statistical software IBM SPSS version 20. The data will be analysed using intention-to-treat principle. A subsequent analysis excluding antibiotic users and non-compliance will be conducted. Categorical variables will be presented using descriptive statistics (frequency, percentage, mean and median) whereas continuous data will be presented as mean +/- standard deviation. Repeated measures analysis of covariance will be used to compare the 2 groups. For continuous data, an independent t-test will
be performed (Mann–Whitney if non-parametric) will be employed for comparisons of the 2 groups. On the other hand, chi-square test and Fisher’s exact test will be used for comparisons of categorical data. A priori level of significance of 0.05 is set for the study.

The number of participants is calculated using the Power and Sample Size Calculations Software version 3.1.2 (Vanderbilt, USA), based on the 1% reduction of HbA1c as outlined by UKPDS Group, 1998. The sample size had been calculated with the consideration of test power 80%, two tailed 95% confidence level and 20% attrition rate, which generate about 100 patients(50 patients per arm) that needed for this study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2015
Actual
1/12/2015
Date of last participant enrolment
Anticipated
31/12/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
70
Final
Recruitment outside Australia
Country [1] 7092 0
Malaysia
State/province [1] 7092 0
Selangor

Funding & Sponsors
Funding source category [1] 291840 0
Government body
Name [1] 291840 0
Ministry of Education
Country [1] 291840 0
Malaysia
Primary sponsor type
Individual
Name
Dr. Neoh Chin Fen
Address
Level 7, FF3,Faculty of Pharmacy, University of Technology Mara Puncak Alam, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia
Country
Malaysia
Secondary sponsor category [1] 290508 0
None
Name [1] 290508 0
Address [1] 290508 0
Country [1] 290508 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293357 0
Universiti Teknologi MARA Research Ethics Committee
Ethics committee address [1] 293357 0
Universiti Teknologi MARA
40450 Shah Alam Selangor
Ethics committee country [1] 293357 0
Malaysia
Date submitted for ethics approval [1] 293357 0
18/11/2014
Approval date [1] 293357 0
01/09/2015
Ethics approval number [1] 293357 0
600-RMI (5/1/6)

Summary
Brief summary
Diabetes mellitus is a looming epidemic worldwide, posing substantial burden on global health and economy. The prevalence of type 2 diabetes mellitus (T2DM) continues to increase and is expected to reach 592 million by 2035. Low grade chronic inflammation has been associated with the onset of T2DM. Probiotics, which are health promoting live microorganisms, may influence the levels of endotoxin and gut hormones thus, improving the glycaemic control in T2DM patients. Therefore, the aim of this study is to investigate the effects of probiotics on glycaemic control in T2DM patients. A total of 100 consenting adult T2DM patients will be enrolled in this study and to receive daily probiotics or placebo for 24 weeks. It is anticipated that probiotics will induce beneficial changes in gut microbiota, reduce systemic inflammatory state and increase secretion of gut hormones, leading to improved glycaemic control and quality of life in T2DM patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59546 0
Dr Neoh Chin Fen
Address 59546 0
Collaborative Drug Discovery Research group, Faculty of Pharmacy, Puncak Alam Campus, Universiti Teknologi MARA (UiTM), 42300 Puncak Alam Selangor
Country 59546 0
Malaysia
Phone 59546 0
+60332584708
Fax 59546 0
Email 59546 0
[email protected]
Contact person for public queries
Name 59547 0
Neoh Chin Fen
Address 59547 0
Collaborative Drug Discovery Research group, Faculty of Pharmacy, Puncak Alam Campus, Universiti Teknologi MARA (UiTM), 42300 Puncak Alam Selangor
Country 59547 0
Malaysia
Phone 59547 0
+60332584708
Fax 59547 0
Email 59547 0
[email protected]
Contact person for scientific queries
Name 59548 0
Neoh Chin Fen
Address 59548 0
Collaborative Drug Discovery Research group, Faculty of Pharmacy, Puncak Alam Campus, Universiti Teknologi MARA (UiTM), 42300 Puncak Alam Selangor
Country 59548 0
Malaysia
Phone 59548 0
+60332584708
Fax 59548 0
Email 59548 0
[email protected]

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