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Trial registered on ANZCTR


Registration number
ACTRN12621000714886
Ethics application status
Approved
Date submitted
5/05/2021
Date registered
8/06/2021
Date last updated
17/11/2022
Date data sharing statement initially provided
8/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of 3FDC dietary supplementation on psychological functioning in an adult population
Scientific title
The effects of 3FDC dietary supplementation on psychological functioning in an adult population with elevated depression, anxiety or stress symptoms
Secondary ID [1] 304135 0
Nil known
Universal Trial Number (UTN)
U1111-1268-8682
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psychological Health 321826 0
Depression 321827 0
Anxiety 321828 0
Stress 322232 0
Gut Function 322233 0
Biochemical Health 322234 0
Condition category
Condition code
Mental Health 319558 319558 0 0
Other mental health disorders
Mental Health 319559 319559 0 0
Studies of normal psychology, cognitive function and behaviour
Mental Health 319925 319925 0 0
Anxiety
Mental Health 319926 319926 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active Intervention: Dosed with oral 3FDC mini-tablets, equivalent to 1200 mg sodium butyrate, twice a day for 6 weeks.

Compliance will be monitored throughout the study. Participants will complete a daily record via a mobile app or a paper-based log for the duration of the 6-week intervention period to record study protocol compliance. Any queries from the logs will be followed up via a phone call. Participants who consume less than 80% of the required product in a given fortnight will receive a courtesy call from site study staff to problem solve compliance issues. Subjects will be instructed to bring back any remaining product to site for accountability purposes.
Intervention code [1] 320474 0
Treatment: Drugs
Comparator / control treatment
Placebo Control: Dosed with oral matching placebo twice a day for 6 weeks. The placebo will be comprised of microcrystalline cellulose coated in the same enteric coating as the treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 327421 0
Change in Hospital Anxiety and Depression Scale (HADS) anxiety and depression subscale scores
Timepoint [1] 327421 0
Baseline, 2 weeks, 4 weeks and 6 weeks (primary timepoint) after intervention commencement
Secondary outcome [1] 395070 0
Change in psychological health assessed using the Depression and Anxiety Stress Scale (DASS-21; subscale scores on the depression, anxiety and stress symptom domains)
Timepoint [1] 395070 0
Baseline, 2 weeks, 4 weeks and 6 weeks after intervention commencement
Secondary outcome [2] 395071 0
Change in psychological health assessed using the Perceived Stress Scale (PSS)
Timepoint [2] 395071 0
Baseline, 2 weeks, 4 weeks and 6 weeks after intervention commencement
Secondary outcome [3] 395072 0
Change in psychological health assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)
Timepoint [3] 395072 0
Baseline, 2 weeks, 4 weeks and 6 weeks after intervention commencement
Secondary outcome [4] 395073 0
Change in psychological health assessed using the Penn State Worry Questionnaire (PSWQ)
Timepoint [4] 395073 0
Baseline, 2 weeks, 4 weeks and 6 weeks after intervention commencement
Secondary outcome [5] 395074 0
Gut symptoms and intestinal comfort assessed using the Gastrointestinal Symptom Rating Scale (GSRS)
Timepoint [5] 395074 0
Baseline, 2 weeks, 4 weeks and 6 weeks after intervention commencement
Secondary outcome [6] 395075 0
Changes in vagus nerve activity as indicated by resting heart rate variability using a finger sensor monitor
Timepoint [6] 395075 0
Baseline and 6 weeks after intervention commencement
Secondary outcome [7] 395076 0
Changes in habitual dietary intake (total intake, macro- and micro-nutrient intake) assessed using 24-hour weighed food records
Timepoint [7] 395076 0
Baseline and 6 weeks after intervention commencement
Secondary outcome [8] 395077 0
Vital signs using measures of blood pressure assessed with a clinical grade automated blood pressure machine, heart rate assessed with a finger sensor monitor, body temperature assessed with a digital thermometer, and respiratory rate assessed by counting the number of times the chest rises per minute while at rest,
Timepoint [8] 395077 0
Baseline and 6 weeks after intervention commencement
Secondary outcome [9] 395078 0
Biochemical safety parameters as assessed by a blood sample, including: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), lactate dehyrogenase (LD), creatinine, creatinine kinase, urea nitrogen, sodium, potassium, chloride, bicarbonate, urea, calcium, C-reactive protein (CRP), uric acid, phosphate, albumin, globulins, protein, total bilirubin, glucose
Timepoint [9] 395078 0
Baseline and 6 weeks after intervention commencement
Secondary outcome [10] 395079 0
Haematological safety parameters as assessed by a blood sample, including: haemoglobin, red blood cell count (RBC), red cell distribution (RDW), packed cell volume (PCV), mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), platelets, white cell count (WCC), neutrophils, lymphocytes, monocytes, eosinophils, basophils
Timepoint [10] 395079 0
Baseline and 6 weeks after intervention commencement
Secondary outcome [11] 395086 0
Incidence of participant reported serious adverse events and adverse events assessed in accordance with the International Conference on Harmonisation Good Clinical Practice (ICH-GCP) guidelines.
Timepoint [11] 395086 0
Baseline and 6 weeks after intervention commencement
Secondary outcome [12] 395087 0
Changes in use of concomitant medications assessed by participant self-report.
Timepoint [12] 395087 0
Baseline and 6 weeks after intervention commencement

Eligibility
Key inclusion criteria
1. Willing to provide written Informed Consent
2. Access to a smartphone and willing to download a free application from the app store
3. Able to access own email address
4. Male or female
5. Aged greater than or equal to 18 & <56 years
6. Body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than or equal to 35 kg/m2 confirmed at clinic screening
7. Scores in the mild range on a minimum of two of the DASS-21 subscales (Depression: greater than or equal to 10 & less than or equal to 13, Anxiety: greater than or equal to 8 & less than or equal to 9, Stress: greater than or equal to 15 & less than or equal to 18) or scores in the moderate range on a minimum of one of the subscales (Depression: greater than or equal to 14 & less than or equal to 20, Anxiety: greater than or equal to 10 & less than or equal to 14, Stress: greater than or equal to 19 & less than or equal to 25) and no scores in the severe or extremely severe range on any of the subscales (Depression: greater than or equal to 21, Anxiety: greater than or equal to 15, and Stress: greater than or equal to 26).
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Use of any of the following types of supplements within 28 days of clinic screening and not prepared to abstain from use for the study duration:
• Supplements containing prebiotics or probiotics
• Fibre supplements (e.g., psyllium plant sterols, Metamucil, Benefibre)
2. Use of any of the following types of prescribed medications within 84 days of clinic screening (for a full list see Appendix A):
• Antidepressants
• Anxiolytics
• Narcotics
• Stimulants
• Anti-psychotics
• Antibiotics
• Systemic steroids (e.g., prednisolone)
• Chronic drug therapy that interferes with vitamin D metabolism, such as glucocorticoids (e.g., dexamethasone)
3. Currently participating in psychological therapy with a mental health clinician (including but not limited to psychologist, counsellor, GP)
4. Participation in nightshift work within 28 days of clinic screening
5. Have a significant acute or chronic illness (psychiatric, gastrointestinal, cardiovascular [except uncontrolled hypertension], endocrine or immunological) or any condition that in the opinion of the PI or Designee may affect the applicant’s ability to participate in the study or the study results
6. Have experienced a cardiovascular event such as congestive heart failure, heart attack, stroke or angina (chest pain) in the past 84 days
7. Currently have, or have a history of, inflammatory bowel disease (e.g., ulcerative colitis, Chron’s disease)
8. Have had previous brain surgery, heart surgery (.e.g., coronary artery bypass surgery), gastrointestinal surgery or other surgery that in the opinion of the PI or Designee may affect the participant’s ability to participate in the study or the study results
9. Smoking/vaping (i.e., history of smoking/vaping within the last six months)
10. Women of childbearing potential (WOCBP) who:
a) Are not currently using effective methods of contraception and
b) Have not been using effective methods of contraception for 14 days prior to clinic screening and
c) Are not willing to use effective methods of contraception throughout the study
11. WOCBP who are currently pregnant or lactating
12. Aversion and/or intolerance/allergy to cellulose
13. Currently hospitalised or any planned hospitalisations during the study that may affect the participant’s ability to comply with the study in the opinion of the Principal Investigator
14. Participated in a clinical trial within 28 days prior to clinic screening that in the opinion of the PI or Designee may affect the applicant’s ability to participate in the study or the study results
15. Blood haematology and biochemistry test results outside the normal reference range at screening and considered clinically significant by the PI or Designee

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)
At phone screening, the applicant will be assigned a unique screening number in a sequential manner. This number will be used for the phone and clinic screening visits only.

After the participants’ eligibility has been established at the baseline visit, the Principial Investigator (or designee) will access an independently managed web-based automated randomisation service (IWRS).

If a participant withdraws from the study or is unable to complete the study for any reason after being randomised, their unique participant ID and intervention allocation will not be reissued to a new participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The Principal Investigator (or designee) will provide the participant’s Dass-21 score, sex, age, and BMI enabling the system to randomly assign the participant to an intervention condition whilst balancing groups on these key variables (through a process of minimisation).
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
N/A
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
It was calculated that a sample size of N=100 provides high power (~95%) to detect the minimal clinically important difference corresponding to a change greater than or equal to 1.5 points on the primary outcome, the Hospital Anxiety and Depression Scale (effect size Cohen’s f=.15; a=.05). This estimate allows for attrition of 15% after which, we would still have sufficient power (~90%) to detect an effect of the same magnitude.

There are no planned interim analyses of any study outcomes. Therefore, a full statistical analysis plan will be developed prior to completion of the study. The analysis plan will detail intention for both primary and secondary outcomes. It is envisaged that analysis will focus on generalised linear mixed models. Outcomes will be analysed on an intention to treat (ITT) and per protocol basis for all participants. Outcomes to be compared between the study groups include psychological wellness and mood, gut function, dietary intake, and biochemical outcomes. The primary analyses will involve 2-way comparisons between the active intervention and the placebo control group.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
During a review of all aspects of Anatara Lifesciences' clinical trials, it became apparent that the sample size required to detect a signal in this 3FDC study may be higher than initially proposed.
Date of first participant enrolment
Anticipated
14/03/2022
Actual
6/04/2022
Date of last participant enrolment
Anticipated
3/10/2022
Actual
29/08/2022
Date of last data collection
Anticipated
14/11/2022
Actual
7/10/2022
Sample size
Target
100
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 308513 0
Commercial sector/Industry
Name [1] 308513 0
Anatara Lifesciences
Country [1] 308513 0
Australia
Funding source category [2] 308515 0
Government body
Name [2] 308515 0
The Commonwealth of Australia represented by the Department of Industry, Science, Energy and Resources
Country [2] 308515 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Anatara Lifesciences
Address
Level 3/62 Lygon St., Carlton, Melbourne VIC 3053 Australia
Country
Australia
Secondary sponsor category [1] 309369 0
None
Name [1] 309369 0
Address [1] 309369 0
Country [1] 309369 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308471 0
CSIRO Health and Medical Human Research Ethics Committee
Ethics committee address [1] 308471 0
Ethics committee country [1] 308471 0
Australia
Date submitted for ethics approval [1] 308471 0
09/02/2021
Approval date [1] 308471 0
19/04/2021
Ethics approval number [1] 308471 0
2021_014_HREC

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110806 0
Dr Ian Zajac
Address 110806 0
Research Scientist/Clinical Psychologist
Nutrition and Health Program, Health & Biosecurity, CSIRO
SAHMRI (South Australian Health and Medical Research Institute), North Terrace, Adelaide, South Australia 5000
Country 110806 0
Australia
Phone 110806 0
+61 8 8303 8875
Fax 110806 0
Email 110806 0
[email protected]
Contact person for public queries
Name 110807 0
Ian Zajac
Address 110807 0
Research Scientist/Clinical Psychologist
Nutrition and Health Program, Health & Biosecurity, CSIRO
SAHMRI (South Australian Health and Medical Research Institute), North Terrace, Adelaide, South Australia 5000
Country 110807 0
Australia
Phone 110807 0
+61 8 8303 8875
Fax 110807 0
Email 110807 0
[email protected]
Contact person for scientific queries
Name 110808 0
Ian Zajac
Address 110808 0
Research Scientist/Clinical Psychologist
Nutrition and Health Program, Health & Biosecurity, CSIRO
SAHMRI (South Australian Health and Medical Research Institute), North Terrace, Adelaide, South Australia 5000
Country 110808 0
Australia
Phone 110808 0
+61 8 8303 8875
Fax 110808 0
Email 110808 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
No IPD sharing has been approved under the ethics approval for this study


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.