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Trial registered on ANZCTR


Registration number
ACTRN12622001078741
Ethics application status
Approved
Date submitted
2/08/2022
Date registered
4/08/2022
Date last updated
19/01/2024
Date data sharing statement initially provided
4/08/2022
Date results information initially provided
14/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of two probiotic formulations on mental health and mood biomarkers in adults with depressive symptoms
Scientific title
Effect of two probiotic formulations on mental health and mood biomarkers in adults with depressive symptoms: A pilot randomized placebo-controlled trial.
Secondary ID [1] 307684 0
None
Universal Trial Number (UTN)
U1111-1281-0892
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 327225 0
Anxiety 327226 0
Insomnia 327227 0
Condition category
Condition code
Mental Health 324361 324361 0 0
Depression
Mental Health 324362 324362 0 0
Anxiety
Alternative and Complementary Medicine 324363 324363 0 0
Other alternative and complementary medicine
Inflammatory and Immune System 324364 324364 0 0
Other inflammatory or immune system disorders
Neurological 324399 324399 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Probiotic capsules containing Bifidobacterium adolescentis (1 capsule taken orally, once daily in the morning, delivering 5 billion colony-forming units a day for 12 weeks) or Probiotic capsules containing Lacticaseibacillus rhamnosus LGG and Bifidobacterium BB-12 (1 capsule taken orally, once daily in the morning, delivering 1 billion colony-forming units a day for 12 weeks). Adherence to capsule intake will be measured by capsule return at weeks 6 and 12.
Intervention code [1] 324160 0
Treatment: Other
Comparator / control treatment
Placebo (containing maltodextrin and microcrystalline cellulose) is matched to the probiotic capsules in terms of taste and appearance but does not contain any of the active ingredients.
Control group
Placebo

Outcomes
Primary outcome [1] 332161 0
Change in Beck Depression Inventory-II score
Timepoint [1] 332161 0
Day 0, week 6, and 12 (primary endpoint) post-intervention commencement
Secondary outcome [1] 412425 0
Change in Beck Anxiety Inventory score
Timepoint [1] 412425 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [2] 412426 0
Change in Depression, Anxiety, and Stress Scale - 21 score
Timepoint [2] 412426 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [3] 412427 0
Change in PROMIS Sleep Disturbance and Sleep-Related Impairment Scale score
Timepoint [3] 412427 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [4] 412428 0
Change in Brain-derived neurotrophic factor blood concentration
Timepoint [4] 412428 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [5] 412429 0
Change in tumor necrosis factor-alpha blood concentration
Timepoint [5] 412429 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [6] 412430 0
Change in interleukin-6 blood concentration
Timepoint [6] 412430 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [7] 412431 0
Change in interleukin-1beta blood concentration
Timepoint [7] 412431 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [8] 412432 0
Change in high sensitivity C-reactive protein blood concentration
Timepoint [8] 412432 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [9] 412433 0
Change in interferon-gamma blood concentration
Timepoint [9] 412433 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [10] 412434 0
Change in lipopolysaccharide-binding protein blood concentration
Timepoint [10] 412434 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [11] 412435 0
Change in intestinal fatty acid-binding protein blood concentration
Timepoint [11] 412435 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [12] 412436 0
Change in blood cortisol concentration
Timepoint [12] 412436 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [13] 412437 0
Change in hair cortisol concentration
Timepoint [13] 412437 0
Day 0 and week 12 post-intervention commencement
Secondary outcome [14] 412438 0
Change in heart rate variability as measured by electrocardiogram (ECG) measurements using a heart rate monitor strap
Timepoint [14] 412438 0
Day 0, week 6, and 12 post-intervention commencement
Secondary outcome [15] 412439 0
Change in microbial stool profile as measured by a stool sample collection using shotgun metagenomic sequencing
Timepoint [15] 412439 0
Day 0 and week 12 post-intervention commencement

Eligibility
Key inclusion criteria
1. Generally healthy adults (male and female) 18 to 65 years
2. Currently experience mild to moderate depressive symptoms as indicated by a score of between 20 and 40 on the BDI-II at both the screening and baseline visit
3. Body mass index (BMI) between 18.5 and 30.0 kg/m2
4. Non-smoker
5. No plan to change dietary or exercise habits during the study period
6. No recent history (within 3 months) or plan to commence new treatments over the study period
7. Willing and able to take probiotic/placebo regimen for 12 weeks
8. Understand, willing and able to comply with all study procedures
9. Willing to provide a personally signed and dated informed consent form detailing all pertinent aspects of the trial.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Suffering from recently diagnosed or unmanaged medical conditions including but not limited to: diabetes, hyper/hypotension, cardiovascular disease, a gastrointestinal disease requiring regular use of medications, gallbladder disease, autoimmune disease, endocrine disease, acute or chronic pain condition, or cancer/malignancy
2. Diagnosis of psychiatric or neurological conditions including but not limited to: psychiatric disorders other than mild-to-moderate depression and/or anxiety disorder, or neurological disease (e.g., Parkinson’s, Alzheimer’s disease, intracranial hemorrhage, head or brain injury)
3. Regular medication intake, including but not limited to anticholinergics, anti-epileptics, acetylcholinesterase inhibitors, benzodiazepines, antipsychotics, opioids, or corticosteroids.
4. Within 2 months before screening, the use of pharmaceutical medications, including but not limited to immunosuppressant drugs, antibiotics, and steroids
5. Change in medication (dose or type) in the last 3 months or an expectation to change during the study duration. Permitted medications include, but are not limited to, pharmaceutical antidepressants such as selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs), cholesterol-lowering medications, antihypertensives, proton pump inhibitors, and thyroid medications,
6. Use of probiotics or mood support supplement up to 4 weeks before study commencement
7. Current or 12-month history of illicit drug abuse
8. Alcohol intake greater than 14 standard drinks per week
9. Any significant surgeries over the last year
10. Women who are pregnant, breastfeeding or intend to fall pregnant

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 is concealed through the use of numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation using a randomisation table created by computer software
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 this pilot study, a convenience sample size of 60 adults is planned for recruitment. No sample size calculation has been completed.

Primary end point will be change in BDI-II score from weeks 0 to 12 and analysed using Generalized Linear Mixed Models (GLMM) with treatment (active combined vs placebo) as factor and adjusted for baseline value of BDI-II.

The parametric statistical analysis model is check using QQ residual plots together with Kolmogorov-Smirnov test for normality.

If test for normality for residuals is not passed, values will be log transferred.

If test for normality is not passed when log-transformation is performed, non-parametric statistical analysis will be used (Mann-Whitney test). The non-parametric analysis will be unadjusted.

Comparison between the three individually treatments groups will be performed as exploratory analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/10/2022
Actual
12/10/2022
Date of last participant enrolment
Anticipated
23/01/2023
Actual
23/12/2022
Date of last data collection
Anticipated
3/04/2023
Actual
20/03/2023
Sample size
Target
60
Accrual to date
Final
62
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 311955 0
Commercial sector/Industry
Name [1] 311955 0
Chr. Hansen
Country [1] 311955 0
Denmark
Primary sponsor type
Commercial sector/Industry
Name
Clinical Research Australia
Address
38 Arnisdale Rd Duncraig WA 6023
Country
Australia
Secondary sponsor category [1] 313440 0
None
Name [1] 313440 0
Address [1] 313440 0
Country [1] 313440 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311386 0
National Institute of Integrative Medicine (NIIM) Human Research Ethics Committee
Ethics committee address [1] 311386 0
11-23 Burwood Rd Hawthorn VIC 3122
Ethics committee country [1] 311386 0
Australia
Date submitted for ethics approval [1] 311386 0
12/07/2022
Approval date [1] 311386 0
06/09/2022
Ethics approval number [1] 311386 0
0107E_2022

Summary
Brief summary
In this randomised, double-blind, placebo-controlled study, 60 adults presenting with depressive symptoms will be randomly assigned to receive probiotic capsules containing (1) Bifidobacterium adolescentis (5 billion colony-forming units a day), or (2) Lacticaseibacillus rhamnosus LGG and Bifidobacterium BB-12 (1 billion colony-forming units a day), or (3) a placebo for 12 weeks. We will assess changes in mood and sleep using self-report questionnaires. Changes in blood markers associated with inflammation (tumour necrosis factor-alpha, interleukin -1beta, interleukin-6, interferon-gamma, and high-sensitivity C-reactive protein), intestinal barrier integrity (lipopolysaccharide-binding protein and intestinal fatty acid-binding protein), and brain-derived neurotrophic factor (important for the survival of brain cells) will be assessed over time. We will also assess changes in cortisol (blood and hair), heart rate variability, and the gut microbiome over time.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120910 0
Dr Adrian Lopresti
Address 120910 0
Clinical Research Australia, 38 Arnisdale Road Duncraig WA 6023
Country 120910 0
Australia
Phone 120910 0
+61 08 94487376
Fax 120910 0
Email 120910 0
adrian@clinicalresearch.com.au
Contact person for public queries
Name 120911 0
Dr Adrian Lopresti
Address 120911 0
Clinical Research Australia, 38 Arnisdale Road Duncraig WA 6023
Country 120911 0
Australia
Phone 120911 0
+61 08 94487376
Fax 120911 0
Email 120911 0
adrian@clinicalresearch.com.au
Contact person for scientific queries
Name 120912 0
Dr Adrian Lopresti
Address 120912 0
Clinical Research Australia, 38 Arnisdale Road Duncraig WA 6023
Country 120912 0
Australia
Phone 120912 0
+61 08 94487376
Fax 120912 0
Email 120912 0
adrian@clinicalresearch.com.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?
Individual participant data underlying published results
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
for IPD meta-analyses
How or where can data be obtained?
Access subject to approvals by Principal Investigator (adrian@clinicalresearch.com.au)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.