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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 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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Major Depressive Disorder

Condition category

Condition code

Mental Health

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]

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]

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]

8 weeks

Primary outcome [2]

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]

adverse events/reactions will be measured at weeks 0, 2, 4, 6, 8 and 26

Secondary outcome [1]

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]

Data will be collected at weeks 0, 2 and 8

Secondary outcome [2]

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]

measured at screening, and weeks 2, 4, 6 and 8

Secondary outcome [3]

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]

measured at baseline, and weeks 2, 4, 6 and 8

Secondary outcome [4]

Level of function will be measured using the Sheehan Disability Scale

Timepoint [4]

measured at baseline, and weeks 2, 4, 6 and 8

Secondary outcome [5]

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]

measured at baseline, and weeks 2, 4, 6 and 8

Secondary outcome [6]

Changes in blood biomarkers of neurogenesis (e.g. brain-derived neurotrophic factor)

Timepoint [6]

measured at weeks 0, 2 and 8

Secondary outcome [7]

Changes in cardiometabolic blood parameters, including random lipid profile, random blood sugar levels and HbA1c

Timepoint [7]

measured at weeks 0, 2 and 8

Secondary outcome [8]

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]

measured at week 0, 2 and 8

Secondary outcome [9]

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]

measured at baseline and week 8

Secondary outcome [10]

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]

Measured at weeks 0, 2 and 8

Secondary outcome [11]

Changes in sleep quality will be measured using the Pittsburgh Sleep Quality Index

Timepoint [11]

measured at baseline, and weeks 2, 4, 6 and 8

Secondary outcome [12]

overall improvement will be assessed using the Patient Global Impression of Change

Timepoint [12]

measured at baseline, and weeks 2, 4, 6 and 8

Secondary outcome [13]

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]

measured at weeks 0, 2 and 8

Secondary outcome [14]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Wilson Foundation

Address [1]

Wilson Foundation, PO Box 4658, Sydney, NSW, 2001

Country [1]

Australia

Primary sponsor type

University

Name

Deakin University

Address

75 Pigdon Rd, Waurn Ponds, Geelong, Victoria 3216

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

University

Name [1]

Food and Mood Centre, IMPACT SRC, Deakin University

Address [1]

HERB Building, 299 Ryrie St, Geelong, Victoria 3220

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Barwon Health Research, Ethics, Governance and Integrity

Ethics committee address [1]

PO Box 281, Geelong, Victoria 3220

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

30/03/2021

Approval date [1]

05/07/2021

Ethics approval number [1]

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

Prof Felice Jacka

Address

Food and Mood Centre, HERB Building, 299 Ryrie St, Geelong VIC 3220

Country

Australia

Phone

+61 3 4215 3302

Fax

[email protected]

Contact person for public queries

Name

Jessica Green

Address

Food and Mood Centre, HERB Building, 299 Ryrie St, Geelong VIC 3220

Country

Australia

Phone

+61 3 4215 3302

Fax

[email protected]

Contact person for scientific queries

Name

Jessica Green

Address

Food and Mood Centre, HERB Building, 299 Ryrie St, Geelong VIC 3220

Country

Australia

Phone

+61 3 42153302

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

for privacy and intellectual property reasons

What supporting documents are/will be available?

Current supporting documents:

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
11373	Study protocol				to be published
11374	Statistical analysis plan				to be published

Updated to:

Doc. No.	Type	Citation	Other Details
11373	Study protocol	Study protocol: https://doi.org/10.1186/s40814-023-01235-z	to be published
11374	Statistical analysis plan	Study protocol: https://doi.org/10.1186/s40814-023-01235-z	to be published
23753	Data dictionary		TBC

Results publications and other study-related documents

Documents added manually

Current Study Results

Documents were uploaded by study researchers but have since been removed.

Update to Study Results

Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
4809	Study results article	Yes		Green JE, Berk M, Mohebbi M, et al. Feasibility, A... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.	2023	https://dx.doi.org/10.1177/07067437221150508
Embase	Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial.	2023	https://dx.doi.org/10.1186/s40814-023-01235-z

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically