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Trial registered on ANZCTR


Registration number
ACTRN12617000419369
Ethics application status
Approved
Date submitted
20/03/2017
Date registered
23/03/2017
Date last updated
2/11/2018
Date data sharing statement initially provided
31/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Probiotic and Magnesium orotate combination for the treatment of depression.
Scientific title
A randomised placebo controlled clinical trial investigating the role of a combination of probiotics and magnesium orotate for the management of depression
Secondary ID [1] 291475 0
Nil known
Universal Trial Number (UTN)
U1111-1194-4073
Trial acronym
Linked study record
ACTRN12614000544673

Health condition
Health condition(s) or problem(s) studied:
Depression 302532 0
Condition category
Condition code
Mental Health 302078 302078 0 0
Depression
Alternative and Complementary Medicine 302102 302102 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised two group placebo controlled treatment trial of a probiotic - mg orotate formula designed as a treatment for depression. Active condition participants will be administered four capsules daily of a probiotic formula for the entire study duration which are a combination of (20 bill CFU / day for 8 weeks duration along with magnesium orotate (1600 mg / day) or placebo taken as divided into both morning and evening doses. Participants can decide weather they take them with or without a meal. The probiotic strains to be tested are Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophiles. Each capsule contains 5 billion CFU of probiotic bacteria as well as 25.5mg magnesium salts attached to 400mg of orotate. Adherence to the dosage schedule will be monitored by participant completed dosage logs and research assistant follow up to monitor conformity to the protocol. The product to be tested has the commercial name NRGBiotic and is developed and supplied by Medlab Australia.
Intervention code [1] 297538 0
Treatment: Other
Comparator / control treatment
The control group will take a placebo capsule designed to replicate the look and size of the active formula. Participants will not know if they are allocated to active or placebo conditions. Control participants will be subject to the same measures and intervals of assessment and follow up as the active condition.
Control group
Placebo

Outcomes
Primary outcome [1] 301508 0
Proportion of participants with Beck Depression inventory >10 indicating symptom remission
Timepoint [1] 301508 0
Intake (initial assessment before starting), 2 months to treatment endpoint (completion of the 8 week intervention period) and again at 2 month follow up.
Primary outcome [2] 301510 0
Incidence of dysbiosis assessed by fecal analysis,
Timepoint [2] 301510 0
Fecal tests at intake (initial assessment before starting), and at 2 months treatment endpoint which is the completion of the 8 week intervention period.
Secondary outcome [1] 332883 0
Proportion of participants with a reduction in the inflammatory marker LPS from baseline, assessed using blood samples and analysis.
Timepoint [1] 332883 0
Blood tests at intake (initial assessment before starting), and at 2 months treatment endpoint which is the completion of the 8 week intervention period.
Secondary outcome [2] 332884 0
Proportion of increased participant Quality of Life Quality of Life Scale (QOLS) from baseline.
Timepoint [2] 332884 0
Intake (initial assessment before starting), 2 months to treatment endpoint (completion of the 8 week intervention period) and again at 2 month follow up.
Secondary outcome [3] 332987 0
Proportion of participants on the Outcome Questionnaire(OQ 45) > 63 which indicates non clinical levels of symptom, interpersonal and social function distress.
Timepoint [3] 332987 0
Intake (initial assessment before starting), weekly to treatment endpoint (completion of the 8 week intervention period) and again at 2 month follow up.

Eligibility
Key inclusion criteria
Participants meeting all of the following inclusion criteria will be included in the study: Given that there is personality and mood factors that are involved with the assessment and treatment of depression, comprehensive assessment and management criteria has been developed to ensure a representative sample and participant safety.
Inclusion criteria:
• Participants are diagnosed with depression by a health practitioner.
• Participants have not changed the standard care that they are receiving without consulting a primary care physician regardless of clinical improvement during the study.
• Participants that present with a high degree of comorbidity on Axis I, II, III (ICD-DSM criterion) will be accepted into the study, given that complex mood, personality and health problems are common in patients diagnosed with depression.
• Eligible participants will be 18 years of age with no upper age limit.
• Participants will be asked not to be currently administering any nutritional supplements or any herbal medicines that have been shown to have antidepressant effects (a list will be provided to participants).
• Participants will be advised not to “self-medicate” with probiotic supplements or any prebiotic supplements for the duration of the trial.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Participants will not have been diagnosed with major depression as the primary condition.
• Participants diagnosed with co-morbid schizophrenia, depression as part of bipolar, or current substance misuse will not be eligible.
• Participants with current high suicide risk will not be eligible.
• Participants prescribed any form of antibiotics, currently or during previous 4 weeks may be considered for inclusion (if last 4 weeks, wait for entry).
• Patients currently administering Warfarin will not be eligible.
• Participants who are pregnant or planning pregnancy over 16 weeks will not be eligible.
• Serious physical illness (e.g., serious life threatening illness or palliative care)
• Participants administering medications other than SSRIs/SNRIs, or, SSRIs/SNRIs in conjunction with other antidepressants will not be eligible.
• Participants already taking probiotics under advisement of a health professional will not be eligible.
• Participants with an established or suspected obstructive/central sleep apnoea.

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)
Participants will not be aware of allocated conditions, and randomisation and allocation will be conducted by a statistician who is not part of the the CI team.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The statistician will provide blinded block randomisation for the allocation of participants equally to the control and experimental groups.
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
Repeated measures for changes in psychiatric and biological outcome markers
Regression analysis for relationships between biological data and psychiatric outcomes

Recruitment
Recruitment status
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 in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 22241 0
4000 - Brisbane

Funding & Sponsors
Funding source category [1] 295945 0
Commercial sector/Industry
Name [1] 295945 0
Medlab Clinical LTD
Address [1] 295945 0
Medlab Clinical LTD
66 McCauley
Alexandria, NSW
Australia 2015
Country [1] 295945 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Medlab Clinical LTD
Address
66 McCauley Street
Alexandria NSW 2015
Country
Australia
Secondary sponsor category [1] 294837 0
University
Name [1] 294837 0
Queensland University of Technology
Address [1] 294837 0
2 George Street
Brisbane City
QLD 4000
Country [1] 294837 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297222 0
QUT Office of Research Ethics and Integrity
Ethics committee address [1] 297222 0
GPO Box 2434. Brisbane Qld 4000.
Ethics committee country [1] 297222 0
Australia
Date submitted for ethics approval [1] 297222 0
03/04/2018
Approval date [1] 297222 0
30/04/2018
Ethics approval number [1] 297222 0
Ethics committee name [2] 301823 0
The University Of Queensland Institutional Human Research Ethics Committee A
Ethics committee address [2] 301823 0
Level 3, Brian Wilson Chancellery
The University of Queensland
St Lucia QLD 4072
Ethics committee country [2] 301823 0
Australia
Date submitted for ethics approval [2] 301823 0
13/02/2017
Approval date [2] 301823 0
22/03/2017
Ethics approval number [2] 301823 0
2017000186

Summary
Brief summary
The primary purpose is to develop our published pilot work. This study will evaluate the efficacy of a combined supplement combining orotate and probiotics using a placebo controlled randomsied treatment trial for the treatment of depression.
The study hypotheses relate to:
1. participants taking the active supplement will have significantly reduced symptom scores compared with the placebo group. (psychiatric assessments).
2. participants taking the active supplement will have reduced dysbiosis and blood inflammatory markers compared with the placebo group.
Changes in dysbiosis will be assessed by fecal testing and changes in systemic inflammatory markers will be assessed by by blood tests.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73378 0
Dr Esben Strodl
Address 73378 0
Office B634, Level 6 O Block, Kelvin Grove Campus
Queensland University of Technology
2 George Street
Brisbane City
QLD 4000
Country 73378 0
Australia
Phone 73378 0
+61 07 3138 8416
Fax 73378 0
Email 73378 0
e.strodl@qut.edu.au
Contact person for public queries
Name 73379 0
Dr Matthew Bambling
Address 73379 0
University of Queensland Faculty of Medicine
Kfloor Mental Health Center
Royal Brisbane and Women's Hospital
Herston and Bowen Bridge Road
Herston Queensland, 4006
Country 73379 0
Australia
Phone 73379 0
+61 466532314
Fax 73379 0
Email 73379 0
m.bambling@uq.edu.au
Contact person for scientific queries
Name 73380 0
Dr Matthew Bambling
Address 73380 0
University of Queensland Faculty of Medicine
Kfloor Mental Health Center
Royal Brisbane and Women's Hospital
Herston and Bowen Bridge Road
Herston Queensland, 4006.
Country 73380 0
Australia
Phone 73380 0
+61 466532314
Fax 73380 0
Email 73380 0
m.bambling@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Not applicable