Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000932864
Ethics application status
Approved
Date submitted
15/04/2021
Date registered
16/07/2021
Date last updated
22/11/2022
Date data sharing statement initially provided
16/07/2021
Date results information initially provided
22/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Human Microbiota Transfer Therapy for Depression (The "Moving Moods Pilot Study")
Scientific title
Human Microbiota Transfer Therapy as an adjunctive treatment for Major Depressive Disorder in adults: a pilot randomised controlled trial
Secondary ID [1] 303927 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 321518 0
Condition category
Condition code
Mental Health 319270 319270 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Faecal Microbiota Transplantation via enema, referred to in this study as Human Microbiota Transfer Therapy (HMTT)
Participants will recieve four doses of HMTT via enema over four consecutive days.
Each dose will consist of a 50mL volume of faecal suspension, combined with 10% glycerol delivered into the rectum via a syringe. Participants will be required to retain the enema for thirty minutes. The HMTT will be delivered by a study nurse in a hospital environment. Delivery and direct obsersvation by study nurse will ensure adherence to the intervention.
Intervention code [1] 320239 0
Treatment: Other
Comparator / control treatment
identical placebo product comprised of normal saline solution, 10% glycerol and brown dye
Control group
Placebo

Outcomes
Primary outcome [1] 327150 0
Feasibility of HMTT as an adjunctive treatment for MDD in adults is considered a composite outcome which will be measured by: • the ability to meet recruitment targets (measured by recruitment logs, comparing actual recruitment against projected targets) • participant retention and completion rates (measured by recruitment logs, attrition rates and completeness of data) • adherence to intended protocol (measured by completion of intervention as planned, missed appointments, technical difficulties arising, and completeness of study data) • participant acceptability (measured using the TransCelerate Study Participant Feedback Questionnaire, plus the addition of questions designed specifically for this study) • robustness of study methodology, including effectiveness of blinding and placebo (measured qualitatively based on feedback from researchers throughout and at the conclusion of the study, and a participant and researcher survey to assess blinding)
Timepoint [1] 327150 0
8 weeks
Primary outcome [2] 327598 0
Safety of HMTT as an adjunctive treatment for MDD in adults will be measured by assessment of adverse events/reactions which will be collected through direct observations by the study nurse during administration of the intervention, and by participant report during the intervention and each visit thereafter
Timepoint [2] 327598 0
adverse events/reactions will be measured at weeks 0, 2, 4, 6, 8 and 26
Secondary outcome [1] 393962 0
The degree of microbial ‘engraftment’ by observing differences between gut microbiota composition and compared with donor samples, using whole-genome shot-gun metagenomic sequencing (measured at weeks 0, 2 and 8)
Timepoint [1] 393962 0
Data will be collected at weeks 0, 2 and 8
Secondary outcome [2] 395853 0
Changes in mental health symptomatology measured by the Montgemery-Asberg Depression Rating Scale (MADRS) and the Depression-Anxiety Stress Scale (DASS) (measured at baseline, and weeks 2, 4, 6 and 8)
Timepoint [2] 395853 0
measured at screening, and weeks 2, 4, 6 and 8
Secondary outcome [3] 395854 0
Quality of life will be measured with the Assessment of Quality of Life-8 Dimension (AQoL-8D); this scale also allows the calculation of preference-based outcomes also known as utilities. Utility values will be used to calculate quality adjusted life years (QALYs) a common metric used in economic evaluations (measured at baseline, and weeks 2, 4, 6 and 8)
Timepoint [3] 395854 0
measured at baseline, and weeks 2, 4, 6 and 8
Secondary outcome [4] 395855 0
Level of function will be measured using the Sheehan Disability Scale
Timepoint [4] 395855 0
measured at baseline, and weeks 2, 4, 6 and 8
Secondary outcome [5] 395856 0
Changes in gut symptomology will be measured using the Gastrointestinal Symptom Rating Scale (GSRS) (measured at baseline, and weeks 2, 4, 6 and 8
Timepoint [5] 395856 0
measured at baseline, and weeks 2, 4, 6 and 8
Secondary outcome [6] 395857 0
Changes in blood biomarkers of neurogenesis (e.g. brain-derived neurotrophic factor)
Timepoint [6] 395857 0
measured at weeks 0, 2 and 8
Secondary outcome [7] 395858 0
Changes in cardiometabolic blood parameters, including random lipid profile, random blood sugar levels and HbA1c
Timepoint [7] 395858 0
measured at weeks 0, 2 and 8
Secondary outcome [8] 395859 0
Changes in metabolic and cardiovascular risk factors assessed via physical exam, including heart rate, blood pressure, weigh circumference, height and weight (measured at week 0, 2 and 8)
Timepoint [8] 395859 0
measured at week 0, 2 and 8
Secondary outcome [9] 395860 0
Cost effectiveness will be assessed from both health sector and societal perspectives. The cost of FMT via enema will be estimated and added to the cost of lost productivity and health care resources utilised by participants over the course of the trial using the Resource Utilization Questionnaire (measured at baseline and week 8)
Timepoint [9] 395860 0
measured at baseline and week 8
Secondary outcome [10] 396488 0
The functional potential between baseline and follow-up, and compared with donor samples, using whole-genome shot-gun metagenomic sequencing (measured at weeks 0, 2 and 8)
Timepoint [10] 396488 0
Measured at weeks 0, 2 and 8
Secondary outcome [11] 396489 0
Changes in sleep quality will be measured using the Pittsburgh Sleep Quality Index
Timepoint [11] 396489 0
measured at baseline, and weeks 2, 4, 6 and 8
Secondary outcome [12] 396490 0
overall improvement will be assessed using the Patient Global Impression of Change
Timepoint [12] 396490 0
measured at baseline, and weeks 2, 4, 6 and 8
Secondary outcome [13] 396491 0
Changes in inflammation (e.g., macrophage inhibitory factor, interleukins 1b, 1ra, 6 and 10, soluble CD14, and high sensitivity C-reactive protein) will be measured in plasma using immunoassays (e.g. solid phase sandwich ELISA assay).
Timepoint [13] 396491 0
measured at weeks 0, 2 and 8
Secondary outcome [14] 396492 0
Changes in gut permeability (e.g., lipopolysaccharide binding protein and zonulin) will be measured in plasma using immunoassays (e.g. solid phase sandwich ELISA assay).
Timepoint [14] 396492 0
measured at weeks 0, 2 and 8

Eligibility
Key inclusion criteria
• Adults (age 18-65)
• MDD according to Structured Clinical Interview for DSM-5 (SCID-5) MDD module
• Moderate-to-severe score on MADRS (i.e. score of greater than or equal to 20)
• Have been on stable pharmaceutical treatment for MDD for one month prior to commencing trial
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Active suicidality (a MADRS suicide item score of 5 or 6)
• Use of probiotics, antibiotics or any experimental drug in the one month prior to study entry
• Serious gastrointestinal conditions (including inflammatory bowel disease, bowel cancer, diverticular disease, or a history of major bowel surgery, but not including irritable bowel syndrome, chronic diarrhoea or constipation)
• Pregnancy or breastfeeding (pregnancy will be determined in females using a urine pregnancy test at baseline)
• Comorbid psychiatric disturbances including bipolar disorder, a primary psychotic illness, obsessive-compulsive disorder, anorexia nervosa or bulimia nervosa
• Active substance-use disorder, defined as a score of 6 or greater on the brief Drug Abuse Screening Test (DAST-10), and/or a score of 16 or greater in the Alcohol Use Disorders Identification Test (AUDIT)
• Inability to read and understand the participant information and informed consent form
• Patients with a history of severe anaphylactic or anaphylactoid food allergy
• A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study

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)
To maintain the allocation concealment, after eligibility is confirmed, the independent unblinded researcher will be contacted to obtain the next allocation. Trial clinicians will allocate packs sequentially, and packaging will be identical so as to conceal treatment allocation and blinding. To facilitate the double-blinding process, the trial products will be prepared by an independent pharmacist. The trial biostatistician and clinicians, as well as participants, will be blinded to group allocations.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation to treatment arms will be randomly assigned in a 2:1 ratio using permutated block randomisation. An independent unblinded researcher utilising a block randomisation with variable block sizes, will develop the computer-generated randomisation sequence and assign participants to study arms.
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 analyses will be conducted in accordance with the International Conference on Harmonization (ICH) E9 statistical principles and include randomised participants with at least one post-baseline observation (intention to treat population). Reporting of findings will be in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines. The study biostatistician responsible for the analysis of outcome data, as well as participants and patient assessors, will be blind to group allocation. The primary efficacy analysis will assess average between-group treatment group differences for the primary outcome measure MADRS total score over the entire study period and will use a likelihood based mixed-effects model, repeated measures approach (MMRM).
The economic evaluation will calculate incremental cost effectiveness ratios (ICERs) from both health sector and societal perspectives. An ICER is calculated by dividing the mean difference in total costs of FMT compared to the placebo group by the mean difference in QALYs between FMT and placebo groups. The technique of ‘bootstrapping’ will be used to obtain confidence intervals for cost effectiveness ratios.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/01/2022
Actual
22/03/2022
Date of last participant enrolment
Anticipated
Actual
23/05/2022
Date of last data collection
Anticipated
Actual
20/11/2022
Sample size
Target
15
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 308312 0
Charities/Societies/Foundations
Name [1] 308312 0
Wilson Foundation
Country [1] 308312 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
75 Pigdon Rd, Waurn Ponds, Geelong, Victoria 3216
Country
Australia
Secondary sponsor category [1] 309153 0
None
Name [1] 309153 0
Address [1] 309153 0
Country [1] 309153 0
Other collaborator category [1] 281734 0
University
Name [1] 281734 0
Food and Mood Centre, IMPACT SRC, Deakin University
Address [1] 281734 0
HERB Building, 299 Ryrie St, Geelong, Victoria 3220
Country [1] 281734 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308287 0
Barwon Health Research, Ethics, Governance and Integrity
Ethics committee address [1] 308287 0
PO Box 281, Geelong, Victoria 3220
Ethics committee country [1] 308287 0
Australia
Date submitted for ethics approval [1] 308287 0
30/03/2021
Approval date [1] 308287 0
05/07/2021
Ethics approval number [1] 308287 0

Summary
Brief summary
This study will evaluate the feasibility of Human Microbiota Transfer Therapy (HMTT) for depression in adults. We will aim to recruit 15 participants to recieve a HMTT enema (n=10) or placebo enema (n=5). We will follow up participants for 8 weeks for primary outcome, measures including recruitment, retention, acceptibility, tolerability, and 6 months for safety data. We hypothesise that HMTT will be a safe and feasible treatment for depression in adults. This pilot data will inform a larger randomised controlled trial evaluating efficacy of HMTT for depression, scheduled to commence in 2022.
Trial website
https://foodandmoodcentre.com.au/projects/moving-moods-can-human-microbiome-transfer-therapy-be-used-as-an-effective-treatment-for-depression-in-adults/
Trial related presentations / publications
Public notes
The protocol allows for the storage of bloods for future analyses of inflammation and/or gut permeability yet to be determined and dependant on funding and available evidence at the time of analysis.

Contacts
Principal investigator
Name 110190 0
Prof Felice Jacka
Address 110190 0
Food and Mood Centre, HERB Building, 299 Ryrie St, Geelong VIC 3220
Country 110190 0
Australia
Phone 110190 0
+61 3 4215 3302
Fax 110190 0
Email 110190 0
[email protected]
Contact person for public queries
Name 110191 0
Dr Jessica Green
Address 110191 0
Food and Mood Centre, HERB Building, 299 Ryrie St, Geelong VIC 3220
Country 110191 0
Australia
Phone 110191 0
+61 3 4215 3302
Fax 110191 0
Email 110191 0
[email protected]
Contact person for scientific queries
Name 110192 0
Dr Jessica Green
Address 110192 0
Food and Mood Centre, HERB Building, 299 Ryrie St, Geelong VIC 3220
Country 110192 0
Australia
Phone 110192 0
+61 3 42153302
Fax 110192 0
Email 110192 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
for privacy and intellectual property reasons


What supporting documents are/will be available?

Current supporting documents:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11373Study protocol    to be published
11374Statistical analysis plan    to be published


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11373Study protocolStudy protocol: https://doi.org/10.1186/s40814-023-01235-z    to be published
11374Statistical analysis planStudy protocol: https://doi.org/10.1186/s40814-023-01235-z   to be published
23753Data dictionary    TBC

Results publications and other study-related documents

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

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4809Study results articleYes Green JE, Berk M, Mohebbi M, et al. Feasibility, A... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFeasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.2023https://dx.doi.org/10.1177/07067437221150508
EmbaseSafety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial.2023https://dx.doi.org/10.1186/s40814-023-01235-z
N.B. These documents automatically identified may not have been verified by the study sponsor.