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Trial registered on ANZCTR


Registration number
ACTRN12619000140156
Ethics application status
Approved
Date submitted
16/01/2019
Date registered
30/01/2019
Date last updated
11/02/2020
Date data sharing statement initially provided
30/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigation of the efficacy and safety of Zao Ren An Shen (ZRAS) capsule for chronic insomnia
Scientific title
Impact of Zao Ren An Shen (ZRAS) capsule on chronic insomnia patients' insomnia severity: A randomized-controlled trial
Secondary ID [1] 297077 0
Nil known
Universal Trial Number (UTN)
U1111-1226-7866
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic insomnia 311083 0
Condition category
Condition code
Mental Health 309717 309717 0 0
Other mental health disorders
Alternative and Complementary Medicine 309718 309718 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational product is Zao Ren An Shen (ZRAS) capsule, a Chinese herbal medicine manufactured product. This product is listed in the ARTG under "Zaoren Anshen" with the approval number 301484.
In this trial, ZRAS capsule will be provided by a PhD student trained in Chinese medicine to the participant individually in a face-to-face fashion at the trial site. The participant will be asked to take orally 3 capsules (2.28g) of ZRAS capsule once daily one hour before bedtime, for 4 weeks.
At the end of the intervention, the participants will be asked to return the drug bottles in order to assess adherence to treatment.
Intervention code [1] 313352 0
Treatment: Other
Comparator / control treatment
A placebo that matches the active in terms of appearance and taste will be used as a comparator.
The participant will be asked to take orally 3 capsules once a day one hour before bedtime.
The composition of the placebo is as following:
• Microcrystalline cellulose 200mg
• Calcium hydrogen phosphate dehydrate 300mg
• Carob pod powder 200mg
• Silicon dioxide 10mg
• Magnesium stearate 10mg
• Hypromellose (capsule shell) 118mg
Control group
Placebo

Outcomes
Primary outcome [1] 318683 0
Insomnia severity assessed with the Insomina Severity Scale
Timepoint [1] 318683 0
Post-treatment (week 4)
Secondary outcome [1] 365681 0
Insomnia severity assessed with the Insomnia Severity Scale
Timepoint [1] 365681 0
mid-treatment (week 2) and follow-up (week 8)
Secondary outcome [2] 365682 0
Total sleep time measured with the sleep diary
Timepoint [2] 365682 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [3] 365683 0
Sleep onset latency measured with the sleep diary
Timepoint [3] 365683 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [4] 365684 0
Wake after sleep onset measured with the sleep diary
Timepoint [4] 365684 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [5] 365685 0
Number of awakenings measured with the sleep diary
Timepoint [5] 365685 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [6] 365686 0
Sleep efficency measured with the sleep diary
Timepoint [6] 365686 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [7] 365688 0
Total sleep time measured with actigraphy
Timepoint [7] 365688 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [8] 365689 0
Sleep onset latency measured with actigraphy
Timepoint [8] 365689 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [9] 365690 0
Wake after sleep onset measured with actigraphy
Timepoint [9] 365690 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [10] 365691 0
Number of awakenings measured with actigraphy
Timepoint [10] 365691 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [11] 365692 0
Sleep efficiency measured with actigraphy
Timepoint [11] 365692 0
mid-treatment (week 1, week 2, week 3), post-treatment (week 4) and follow-up (week 7)
Secondary outcome [12] 365693 0
Depression, anxiety and stress levels measured with the Depression, Anxiety and Stress Scale (DASS)
Timepoint [12] 365693 0
mid-treatment (week 2), post-treatment (week 4) and follow-up (week 8)
Secondary outcome [13] 365694 0
Quality of life measured with the Assessment of Quality of Life (AQoL)
Timepoint [13] 365694 0
mid-treatment (week 2), post-treatment (week 4) and follow-up (week 8)
Secondary outcome [14] 365695 0
fatigue severity measured with the Fatigue Severity Scale (FSS)
Timepoint [14] 365695 0
mid-treatment (week 2), post-treatment (week 4) and follow-up (week 8)
Secondary outcome [15] 365696 0
adverse events will be assessed with interviews and recorded in an Adverse Event Forms designed for this study.
Adverse events recorded during previous clinical trials are fatigue, stomach discomfort, diarrhoea, acid reflux, and lips numbness.
Timepoint [15] 365696 0
mid-treatment (week 2), post-treatment (week 4) and follow-up (week 8)

Eligibility
Key inclusion criteria
1. 18 years old or older.
2. Complaint of difficulty initiating or maintaining sleep occurring at least three times per week for at least three months despite adequate opportunity to sleep, and resulting in distress or impaired daytime functioning.
3. ISI score greater than or equal to 10.
4. Willing to abstain from any other treatment for insomnia, including pharmaceutical treatment, CAM, and psychotherapy, during the baseline and intervention periods.
5. Willing to use birth control methods and to not donate sperm during the baseline and intervention periods, or sterile.
6. Ability to understand and speak English.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Imminent need of psychiatric (e.g., suicide risk) or medical care (e.g., stroke).
2. Abnormal blood tests, including Full Blood Count (FBC), Liver Function Test (LFT), and Electrolytes-Urea-Creatinine (EUC), within the last six months, if not approved by a general practitioner.
3. No evidence that substance use (e.g., caffeine or a medication), coexisting medical conditions or mental disorders, including sleep-wake disorder, do not adequately explain the predominant complaint of insomnia.
4. Use of any treatment for insomnia less than 14 days prior to randomization.
5. Any psychotic disorder or bipolar disorder if not appropriately treated or stable for less than two years.
6. Alcohol or drug addiction.
7. Other mental disorders such as major depressive disorder or generalized anxiety disorder, if the disorder is untreated or treated for less than one month.
8. Cognitive impairment preventing the participant to understand the trial instructions, complete questionnaires or provide informed consent.
9. Allergy history to any of the ingredient of the ZRAS capsule or the placebo.
10. Taking a Warfarin-type anticoagulant, quetiapine, clozapine, or olanzapine .
11. Women being pregnant or breast-feeding.
12. Considered not suitable for the trial by the investigator.

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)
The randomisation scheme will be generated by a NICM Heath Research institute (NICM) researcher not directly affiliated with this study to ensure blinding. It will be kept by this researcher during the time of the trial and be revealed only after the end of the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation scheme will be generated by a NICM Heath Research institute (NICM) researcher not directly affiliated with this study to ensure blinding. The methods used is simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation). The sequence generated will be used to identify the investigational product. Both the investigator and the participants will be blinded.
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
There is a one-week placebo run-in before randomization
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size

The standard deviation of the ISI total score in an insomnia population is 4.1. A difference of 7 points between baseline and post-treatment is considered as clinically significant. As placebo would give a decrease of approximately 4 points, the difference between the two groups at post-treatment has to be of 0.73 standard deviations. Using a 0.05 significance level, 90% power and allowing for 10% dropout rate, a sample size of 90 participants, 45 in each group, will be required.

Statistical analysis

The overall baseline instrument scores and demographic information will be analysed to compare with population norms. The baseline characteristics of treatment and control groups will also be compared to confirm randomisation has achieved balanced treatment groups. Where imbalance is detected in the randomised groups due to chance, this will be considered and adjusted for where possible in the statistical analysis. The data will also be checked for normal distribution to confirm the appropriateness of the proposed statistical tests.
Continuous data will be analysed with Linear Mixed effects Model (LMM); mean, standard deviation, effect size, 95% CI and p-value will be reported. Dichotomous data will be analysed with Chi-square and counts, percentages, and p-value will be reported. A significance level of 0.05 will be used. Both an intention-to-treat analysis and a per-protocol analysis will be conducted, the intention-to-treat analysis being of primary interest as it reflects better the effectiveness of the investigational product.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/02/2019
Actual
4/04/2019
Date of last participant enrolment
Anticipated
12/10/2020
Actual
Date of last data collection
Anticipated
13/12/2020
Actual
Sample size
Target
90
Accrual to date
38
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 301644 0
University
Name [1] 301644 0
Western Sydney University
Country [1] 301644 0
Australia
Primary sponsor type
University
Name
Western Sydney University, NICM Health Research Institute
Address
Building J, 158-160 Hawkesbury Rd, Westmead, NSW 2145
Country
Australia
Secondary sponsor category [1] 301353 0
None
Name [1] 301353 0
Address [1] 301353 0
Country [1] 301353 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302366 0
Western Sydney University Human Research Ethics Committee
Ethics committee address [1] 302366 0
Human Ethics Officer
Research Engagement, Development and Innovation (REDI)
Western Sydney University
Locked Bag 1797
Penrith NSW 2751
Ethics committee country [1] 302366 0
Australia
Date submitted for ethics approval [1] 302366 0
Approval date [1] 302366 0
17/12/2018
Ethics approval number [1] 302366 0
H12990

Summary
Brief summary
This study is a randomized-controlled-trial that aims to assess the efficacy and safety of Zao Ren An Shen (ZRAS) capsule, a Chinese herbal medicine product, for chronic insomnia. After a 1-week placebo run-in, the participants will be randomized to either the experimental group or the placebo group and asked to take three capsule of either ZRAS or placebo every day before bedtime for four weeks. The outcomes will be assessed continuously with a sleep diary and actigraphy, and at baseline, mid-treatement (week 2), post-treatment and follow-up (week 8) with questionnnaires about insomnia severity, fatigue severity, psychological status, and quality of life. The hypothesis is that ZRAS is efficient and safe for chronic insomnia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89978 0
Mr Yoann Birling
Address 89978 0
Western Sydney University, NICM Health Research Institute
Building J, 158-160 Hawkesbury Rd, Westmead, NSW 2145
Country 89978 0
Australia
Phone 89978 0
+61 450079285
Fax 89978 0
Email 89978 0
[email protected]
Contact person for public queries
Name 89979 0
Mr Yoann Birling
Address 89979 0
Western Sydney University, NICM Health Research Institute
Building J, 158-160 Hawkesbury Rd, Westmead, NSW 2145
Country 89979 0
Australia
Phone 89979 0
+61 450079285
Fax 89979 0
Email 89979 0
[email protected]
Contact person for scientific queries
Name 89980 0
Mr Yoann Birling
Address 89980 0
Western Sydney University, NICM Health Research Institute
Building J, 158-160 Hawkesbury Rd, Westmead, NSW 2145
Country 89980 0
Australia
Phone 89980 0
+61 450079285
Fax 89980 0
Email 89980 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
In order to protect participant's privacy, the individual participant data will not be shared


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1076Study protocol    not published yet



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseZao Ren An Shen capsule for insomnia: A double-blind, randomized, placebo-controlled trial.2022https://dx.doi.org/10.1093/sleep/zsab266
N.B. These documents automatically identified may not have been verified by the study sponsor.