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Trial registered on ANZCTR


Registration number
ACTRN12623000287639
Ethics application status
Approved
Date submitted
9/03/2023
Date registered
17/03/2023
Date last updated
16/06/2024
Date data sharing statement initially provided
17/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effectiveness of herbal formulations for stress
Scientific title
A randomised placebo-controlled trial investigating effectiveness of two herbal combinations for short-term stress management in healthy adults

Secondary ID [1] 309160 0
None
Universal Trial Number (UTN)
U1111-1289-5575
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stress 329283 0
Condition category
Condition code
Alternative and Complementary Medicine 326235 326235 0 0
Herbal remedies
Mental Health 326236 326236 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment Arm 1 - Herbal tablet containing: Ziziphus jujuba var. spinosa (Ziziphus), Passiflora incarnata (Passionflower), Melissa officinalis (Lemon balm) and Matricaria chamomilla (Chamomile). Three tablets daily, orally, in divided doses, for 21 days.

Treatment Arm 2 - Herbal tablet containing: Withania somnifera (root) and Crocus sativus (stigma). Two tablets daily, orally, in divided doses, for 21 days.

Participants in Treatment Arm #1 will be directed to take , one in the morning, one in middle of day, and one in the evening. Participants in Treatment Arm #2 will be directed to take two tablets, orally, daily, one in the morning, and one in the evening. Compliance will be assessed through returned tablet count on completion of study.

Intervention code [1] 325609 0
Treatment: Drugs
Comparator / control treatment
Placebo tablets containing microcrystaline cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 334107 0
Change in stress, depression and anxiety indices assessed using the Depression, anxiety, stress scale (DASS-21). Analysed as a composite outcome (change in overall DASS-21 score)
Timepoint [1] 334107 0
Baseline and day 21 after treatment randomisation
Secondary outcome [1] 419381 0
Change in stress levels assessed using the Perceived Stress Scale (PSS)
Timepoint [1] 419381 0
Baseline and day 21 after treatment randomisation
Secondary outcome [2] 419382 0
Change in sleep assessed using PROMIS Sleep Scale - adult short-form (PROMIS)
Timepoint [2] 419382 0
Baseline and day 21 after treatment randomisation
Secondary outcome [3] 419383 0
Change in anxiety assessed using Zung Self-Rating Anxiety Scale (Zung) (assessed in Treatment Arm #1 only)
Timepoint [3] 419383 0
Baseline and day 21 after treatment randomisation
Secondary outcome [4] 419384 0
Patient Global Impression of Change
Timepoint [4] 419384 0
Baseline and day 21 after treatment randomisation

Eligibility
Key inclusion criteria
- - Healthy adults (18-75 years)
- - Any allowable prescription medication use by participants must be stable for four weeks or more prior to trial entry
- - Score of 13 or more on the Perceived Stress Scale (PSS-10)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- - Diagnosed depression or anxiety for which person is taking medication or has ceased taking medication within the last four weeks
- - Diagnosed with any of the following medical conditions: cancer (if active within last 5 years and excepting skin cancer), liver or kidney disease, neurological disease
- - Currently unwell with acute infection or fever
- - Having contracted confirmed Covid-19 in the four weeks prior to enrolment
- - In poor general health
- - Taking any of the following medications: anti-depressants; any type of neuro-active medications, i.e. mood stabilisers, stimulants, anti-psychotics; warfarin or anti-coagulant medications, cyclosporin
- - Current use of any herbal medicine or nutrients targeted for mood, stress or mental health (eligibility of participants taking any supplements will be at discretion of enrolling practitioner)
- - Pregnant or breastfeeding or planning pregnancy
- - Allergy/sensitivity to study drugs or their formulations

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)
Before randomisation, participants will be assessed by naturopathic clinicians and allocated to one of two treatment arms based on their initial presentation. Persons presenting with a mild to moderate level of anxiety will be allocated into Treatment Arm #1 and randomised to receive Active or Placebo study medication in a 2:1 ratio. Persons presenting without any significant anxiety symptoms will be allocated into Treatment Arm #2 and randomised to receive Active or Placebo study medication in a 2:1 ratio. Clinicians will be blinded to treatment allocation through the use of pre-randomised numbered study medication bottles.

The prescribing naturopath will be aware of the group allocation, i.e. to Treatment Arm #1 or Treatment Arm #2, but will be unaware of whether the participant has been allocated to Active or Placebo tablets (double-blind).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
An a priori power analysis was undertaken to estimate the required sample size. We predicted a 20% between group difference in DASS-21 mean scores between active and placebo groups with a 2:1 treatment ratio. Assuming a power of 80%, a type 1 error rate (alpha) of 5%, and a 10% drop-out rate, the total number of participants to find an effect was estimated as 50 for each Treatment Arm (35 Active and 15 Placebo for each treatment arm). Therefore, a total of 100 participants will be enrolled.
Analysis of data will be conducted on final locked dataset, with blinding to group allocations. Data analysis will be conducted by an independent statistician.

Treatment Arm #1 and #2 will be analysed separately for changes and scores also analysed as a complete group for all questionnaires except Zung SAS (which will be administered to Treatment Arm #1 only). Changes for the primary outcome will be calculated from baseline to week 3 and compared to placebo using T-tests and general linear regression (GLM) models. The secondary outcomes of PSS, PROMIS Sleep scale and Zung SAS will be calculated from baseline to week 3 and compared to placebo using T-tests and general linear regression (GLM) models. Adverse events will be assessed qualitatively and compared to placebo. All tests of treatment effects will be conducted using a two-sided alpha level of 0.05 and 95% confidence intervals.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
17/04/2023
Actual
17/04/2023
Date of last participant enrolment
Anticipated
Actual
27/09/2023
Date of last data collection
Anticipated
Actual
11/10/2023
Sample size
Target
100
Accrual to date
Final
94
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 313360 0
Commercial sector/Industry
Name [1] 313360 0
Integria Healthcare (Australia) Pty Ltd.
Country [1] 313360 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Integria Healthcare (Australia) Pty Ltd.
Address
Building 5, Freeway Office Park, 2728 Logan Rd, Eight Mile Plains, Qld 4113
Country
Australia
Secondary sponsor category [1] 315123 0
None
Name [1] 315123 0
Address [1] 315123 0
Country [1] 315123 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312581 0
National Institute of Integrative Medicine
Ethics committee address [1] 312581 0
11 Burwood Rd, Hawthorn VIC 3122
Ethics committee country [1] 312581 0
Australia
Date submitted for ethics approval [1] 312581 0
17/01/2023
Approval date [1] 312581 0
20/03/2023
Ethics approval number [1] 312581 0

Summary
Brief summary
This will be a blinded, placebo-controlled clinical trial conducted within natural medicine clinics. Initial screening and consenting of participants will be conducted by the Co-Investigator and participants allocated to individual naturopathic clinicians for assessment interviews. The study includes two active treatment options and a placebo control. Participants will be allocated into Treatment Arm #1 or Treatment Arm #2 based on their initial clinical presentation, categorised into either an ‘anxiety-driven’ stress type (Treatment Arm #1) or a ‘non-anxiety driven’ stress type (Treatment Arm #2).

Participants will be tested for stress, depression and anxiety indices at baseline and at day 21 for changes in these areas.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125170 0
Dr Elizabeth Steels
Address 125170 0
Registered business address: 188 James Street, New Farm, Qld, 4005
Country 125170 0
Australia
Phone 125170 0
+61 428983280
Fax 125170 0
Email 125170 0
[email protected]
Contact person for public queries
Name 125171 0
Elizabeth Steels
Address 125171 0
Registered business address: 188 James Street, New Farm, Qld, 4005
Country 125171 0
Australia
Phone 125171 0
+61 428983280
Fax 125171 0
Email 125171 0
[email protected]
Contact person for scientific queries
Name 125172 0
Elizabeth Steels
Address 125172 0
Registered business address: 188 James Street, New Farm, Qld, 4005
Country 125172 0
Australia
Phone 125172 0
+61 428983280
Fax 125172 0
Email 125172 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
Data is commercial-in-confidence.


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.