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Trial registered on ANZCTR


Registration number
ACTRN12620000294954p
Ethics application status
Submitted, not yet approved
Date submitted
17/02/2020
Date registered
4/03/2020
Date last updated
27/05/2020
Date data sharing statement initially provided
4/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Probiotics and wellbeing in adults with type 1 diabetes
Scientific title
Probiotics and mental health: a randomized controlled trial of probiotics in adults with type 1 diabetes
Secondary ID [1] 300526 0
None
Universal Trial Number (UTN)
U1111-1243-7435
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 316230 0
depression 316231 0
stress 316232 0
anxiety 316233 0
Condition category
Condition code
Mental Health 314518 314518 0 0
Depression
Mental Health 314519 314519 0 0
Anxiety
Metabolic and Endocrine 314520 314520 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a randomised, double-blind, placebo-controlled trial investigating the effects of probiotic versus placebo capsules on depression, anxiety, stress, health-related quality of life, illness beliefs and glycaemic control (HbA1c) among adults with T1D in the Auckland region over the course of 12 weeks. Beliefs around probiotic supplementation will also be examined.
Eighty participants will be recruited from Auckland, Counties Manakau and/or Waitemata District Health Board diabetes outpatient clinics. Participants will also be recruited from online T1D communities (E.g. Facebook support groups).

The probiotic capsules are size 3, opaque, hard hypromellose capsules, each containing 180 mg of a standardized white to light beige fine powder consisting of freeze-dried cultures. The freeze dried culture used in this study is Bifidobacterium (BB-12®) and Lactobacillus rhamnosus (LGG®) (50 % : 50 %). This product has a minimum potency of 6.5 billion (6.5E+9) CFU (Colony Forming Units) per capsule at time of release.

After providing written informed consent, participants will complete baseline questionnaires in clinic. Participants’ HbA1c levels will be accessed through their medical records. Participants will then be randomised to receive probiotic or placebo capsules for 12 weeks and will be given a bottle of capsules and be asked to take one capsule each day. Participants will be sent a text message every two weeks reminding them to take their capsules. Outcome measures will be assessed at baseline (in clinic) and at the 12 weeks follow-up using online questionnaires.

After the 12-week follow-up, 6-10 participants will be invited to attend a focus group and/or interviews to discuss their views on taking probiotics and possible barriers (e.g. cost). This qualitative component will also allow us to explore more in-depth views from Maori participants, who are unlikely to be equally represented in the quantitative data due to T1D being more prevalent in European New Zealanders. With a sample size of 80, we hope to recruit approximately eight Maori participants, out of which we estimate 4-6 will be able to attend the focus group and/or interviews.
Intervention code [1] 316829 0
Treatment: Other
Comparator / control treatment
A randomised, double-blind placebo-controlled design will be used. One half of the participants will receive the probiotic and the other half of the participants will receive a placebo.
The placebo capsules are size 3, opaque, hard hypromellose capsules, each containing 180 mg of a standardized white to light beige fine powder. This powder consists of Maltodextrin, microcrystalline cellulose, magnesium stearate and silicon dioxide. The capsule itself is made up of Hypromellose and titanium dioxide.
Control group
Placebo

Outcomes
Primary outcome [1] 322836 0
Depression scores are assessed by the brief Depression, Anxiety, and Stress Scale (DASS; Lovibond & Lovibond, 1995).
Timepoint [1] 322836 0
Baseline and post-intervention (12 weeks after baseline)
Primary outcome [2] 323081 0
Anxiety scores are assessed by the brief Depression, Anxiety, and Stress Scale (DASS; Lovibond & Lovibond, 1995).
Timepoint [2] 323081 0
Baseline and post-intervention (12 weeks after baseline)
Primary outcome [3] 323082 0
Stress scores are assessed by the brief Depression, Anxiety, and Stress Scale (DASS; Lovibond & Lovibond, 1995).
Timepoint [3] 323082 0
Baseline and post-intervention (12 weeks after baseline)
Secondary outcome [1] 379967 0
Illness perceptions measured by the Brief Illness Perception Questionnaire (Brief-IPQ; Broadbent, Petrie, Main, & Weinman, 2006).
Timepoint [1] 379967 0
Baseline and post-intervention (12 weeks after baseline).
Secondary outcome [2] 379969 0
Health-related quality of life measured by the 15-item Diabetes Quality of Life scale (DQOL-15 item; Burroughs, Desikan, Waterman, Gilin, & McGill, 2004).
Timepoint [2] 379969 0
Baseline and post-intervention (12 weeks after baseline).
Secondary outcome [3] 379970 0
Adherence measured by placing extra placebo capsules and extra probiotic capsules in the bottles and including a question at follow-up asking “Did you have any leftover capsules? If yes, how many?”. The number left over in the bottle will be converted to a percentage for adherence rate. An adherence rate of over 80% is deemed acceptable adherence (Haynes et al., 1980).
Timepoint [3] 379970 0
Post-intervention (12 weeks after baseline).
Secondary outcome [4] 379971 0
Diet measured using the four items assessing diet from the Summary of Diabetes Self-Care Activities scale (Toobert, Hampson, & Glasgow, 2000).
Timepoint [4] 379971 0
Baseline and post-intervention (12 weeks after baseline).
Secondary outcome [5] 379972 0
Glycemic control (HbA1c) levels will be collected from participants medical records as they are routinely recorded as part of standard care (via blood test every 3-4 months).
Timepoint [5] 379972 0
The most recent HbA1c collected prior to intervention and subsequent HbA1c post-intervention (12 weeks after baseline).
Secondary outcome [6] 380724 0
Probiotic knowledge and beliefs will be measured using a qualitative questionnaire on patient experience and use of probiotics (Chin-Lee, Curry, Fetterman, Graybill, & Karpa, 2014).
Timepoint [6] 380724 0
Baseline and post-intervention (12 weeks after baseline)
Secondary outcome [7] 380725 0
Views on taking probiotics and possible barriers (assessed via focus groups/interviews)
Timepoint [7] 380725 0
Post-intervention only (12 weeks after baseline)

Eligibility
Key inclusion criteria
1. Must have had a diagnosis of type 1 diabetes for at least a year
2. Participants must be at least 18 years of age
3. Currently living in Auckland
4. Ability to provide informed consent
5. Ability to understand, read, and write English
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Antibiotic or probiotic treatment within 3 months before enrolment
2. Surgery in the previous 3 months
3. Gastrointestinal infection within 1 month before enrolment
4. Immunodeficiency or immunosuppressed
5. Diagnosed with type 1 diabetes with pancreatitis
6. Pregnancy or breastfeeding

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-based random number generator
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)
Efficacy
Statistical methods / analysis
For our sample size calculation we used the effect size from a study conducted by Akkasheh and colleagues (Akkasheh et al., 2016), who examined the effects of probiotics on depression in patients with major depressive disorder. Using GPower (Faul, Erdfelder, Lang, & Buchner, 2007), it was calculated that a sample of 72 participants would be required to detect a large effect (Cohen’s d=0.7) in depression, using an independent samples t-test with 90% power and an alpha of 0.05. This was increased to 80 (40 in each treatment arm) to allow for attrition.

Independent samples t-tests and linear mixed models will be used to assess differences across the two treatment arms (probiotic versus placebo) over time (baseline and 12-week follow-up). We will also conduct sub-group analyses, where we will examine between-group differences of participants allocated to the probiotic treatment who had the highest depressive symptoms at baseline compared to the control group at 12 weeks.

Pearson’s correlations will be used to explore the relationship between the demographic characteristics, psychosocial factors, glycaemic control, and depression and anxiety. Multiple linear regression will be used to examine which measures are associated with depression or anxiety, as well as to examine possible moderators and mediators.

The qualitative data from the focus groups/interviews will be examined using Thematic Analysis, which is a systematic method of organising qualitative data and finding patterns in the data (Braun & Clarke, 2006). This method of analysis is frequently used to examine information obtained from focus groups, to investigate a priori research questions.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22348 0
New Zealand
State/province [1] 22348 0
Auckland

Funding & Sponsors
Funding source category [1] 304936 0
University
Name [1] 304936 0
The University of Auckland
Address [1] 304936 0
Department of Psychological Medicine
University of Auckland
Private Bag 92019, Victoria Street West
Auckland 1142

Country [1] 304936 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Department of Psychological Medicine
University of Auckland
Private Bag 92019, Victoria Street West
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 305290 0
None
Name [1] 305290 0
Address [1] 305290 0
Country [1] 305290 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305345 0
Health and Disability Ethics Committees
Ethics committee address [1] 305345 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 305345 0
New Zealand
Date submitted for ethics approval [1] 305345 0
05/02/2020
Approval date [1] 305345 0
Ethics approval number [1] 305345 0

Summary
Brief summary
Adults with type 1 diabetes (T1D) are at an increased risk for a range of mental health disorders, in particular depression. Using a randomised, double-blind, placebo-controlled trial, this study will investigate the effects of probiotic versus placebo capsules on depression, anxiety, stress, health related quality of life, illness beliefs and glycaemic control(HbA1c) among adults with T1D in the Auckland region over the course of 12 weeks.
We will also examine beliefs around probiotic supplementation.

Eighty participants will be recruited from Auckland, Counties Manakau and/or Waitemata District Health Board diabetes outpatient clinics. Participants will also be recruited from online T1D communities (E.g. Facebook support groups). Once participants have consented to participate they will complete the baseline questionnaire and be randomised into the placebo or the probiotic group and be given a bottle of capsules and be asked to take one capsule each day. Participants will be asked to complete follow-up questionnaires 12 weeks later. We will also collect their baseline glycaemic control (HbA1c) and their most recent HbA1c measure after the study ends from their medical records.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100074 0
Dr Anna Serlachius
Address 100074 0
Department of Psychological Medicine
University of Auckland
Private Bag 92019, Victoria Street West
Auckland 1142
Country 100074 0
New Zealand
Phone 100074 0
+64 09 923 3073
Fax 100074 0
Email 100074 0
a.serlachius@auckland.ac.nz
Contact person for public queries
Name 100075 0
Dr Anna Serlachius
Address 100075 0
Department of Psychological Medicine
University of Auckland
Private Bag 92019, Victoria Street West
Auckland 1142
Country 100075 0
New Zealand
Phone 100075 0
+64 09 923 3073
Fax 100075 0
Email 100075 0
a.serlachius@auckland.ac.nz
Contact person for scientific queries
Name 100076 0
Dr Anna Serlachius
Address 100076 0
Department of Psychological Medicine
University of Auckland
Private Bag 92019, Victoria Street West
Auckland 1142
Country 100076 0
New Zealand
Phone 100076 0
+64 09 923 3073
Fax 100076 0
Email 100076 0
a.serlachius@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We do not have the participants' consent to share individual participant data from the trial.
What supporting documents are/will be available?
No other documents available
Summary results
No Results