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Trial registered on ANZCTR


Registration number
ACTRN12618001589279p
Ethics application status
Submitted, not yet approved
Date submitted
17/09/2018
Date registered
25/09/2018
Date last updated
25/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial assessing the efficacy and safety of Ziziphus spinosa seeds compared to placebo for people with insomnia
Scientific title
A clinical trial assessing the efficacy and safety of Ziziphus spinosa seeds compared to placebo for people with insomnia
Secondary ID [1] 296107 0
Nil known
Universal Trial Number (UTN)
U1111-1220-5521
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Insomnia 309682 0
Condition category
Condition code
Alternative and Complementary Medicine 308488 308488 0 0
Herbal remedies
Mental Health 308489 308489 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou (Common names: Spine Date Seed or Jujube Seeds; Rhamnaceae family). Dose: 2g once daily; Duration of administration: 4 weeks; Mode of administration: oral tablet.

To monitor adherence to the intervention, participants will return the unused medication and packaging to the researchers for checking and documentation. The participants will return the unused medication and packaging after the two treatment periods.

This is a cross-over study and there will be a 4-week wash out period between treatments.
Intervention code [1] 312440 0
Treatment: Drugs
Comparator / control treatment
Placebo (corn-starch)
Control group
Placebo

Outcomes
Primary outcome [1] 307467 0
Insomnia severity index
Timepoint [1] 307467 0
End of the 4 week treatment period
Secondary outcome [1] 351976 0
Sleep-onset latency (SOL) (measured with sleep diary and verified by actigraphy wristwatch).
Timepoint [1] 351976 0
End of the 4 week treatment period
Secondary outcome [2] 351977 0
Pittsburgh Sleep Quality Index
Timepoint [2] 351977 0
End of the 4 week treatment period
Secondary outcome [3] 351978 0
Depression Anxiety Stress Scales
Timepoint [3] 351978 0
End of the 4 week treatment period
Secondary outcome [4] 351979 0
WHO Quality of Life Instrument (WHOQOL-BREF)
Timepoint [4] 351979 0
End of the 4 week treatment period
Secondary outcome [5] 351980 0
Functional Outcomes of Sleep Questionnaire
Timepoint [5] 351980 0
End of the 4 week treatment period
Secondary outcome [6] 352169 0
Wake time after sleep onset (WASO) (measured with sleep diary and verified by actigraphy wristwatch).
Timepoint [6] 352169 0
End of the 4 week treatment period
Secondary outcome [7] 352170 0
Number of awakenings during the night (measured with sleep diary and verified by actigraphy wristwatch).
Timepoint [7] 352170 0
End of the 4 week treatment period
Secondary outcome [8] 352171 0
Sleep efficiency (SE) (measured with sleep diary and verified by actigraphy wristwatch).
Timepoint [8] 352171 0
End of the 4 week treatment period
Secondary outcome [9] 352172 0
Total sleep time (TST) (measured with sleep diary and verified by actigraphy wristwatch).
Timepoint [9] 352172 0
End of the 4 week treatment period
Secondary outcome [10] 352173 0
Adverse events (number and type). The study medication does not have any known adverse reactions; however, if events occur they will be recorded in the research documentation as a secondary outcome. If adverse events occur they will be assessed by the research investigators. If the participants need follow up or treatment for their adverse events they will be referred back to their usual treating doctor.
Timepoint [10] 352173 0
End of the 4 week treatment periods and during the wash-out period. Details about adverse events will be primarily collected during the visits to the research site at the end of the two treatment periods and the end of the wash out period. In addition, the participants can call the research team at any time to report an adverse event.
Secondary outcome [11] 352174 0
Leeds Sleep Evaluation Questionnaire (safety outcome)
Timepoint [11] 352174 0
End of the 4 week treatment period

Eligibility
Key inclusion criteria
1. Give their written informed consent to participate.
2. At least 18 years of age and no older than 70 years (at Visit 1).
3. Minimum cut-off of at least 10 on the ISI to define insomnia severity.
4. Meet the Chinese medicine criteria for Heart Deficiency (determined by a Chinese medicine practitioner).
5. Meet Diagnostic and Statistical Manual of Mental Disorders (DSM-V) definition of insomnia
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants diagnosed with another sleep disorder (including Obstructive Sleep Apnoea [determined by the Berlin Questionnaire], restless legs syndrome, or narcolepsy).
2. Participants who are using sedatives or hypnotics and are unwilling or unable to discontinue use during the study.
3. Participants using anti-depressants for less than 3 months (or have been using anti-depressants for more than 3 months but have experienced an episode of depression in the previous 3 months).
4. Participants with major depression or other psychopathology (such as bipolar disorder).
5. Participants who are participating in cognitive behavioural therapy for insomnia (CBT-I) within 4 weeks of Visit 1 or who will enter CBT-I during the study period.
6. Participants with serious illness that make them unsuitable for the study (severe heart, liver or kidney disease).
7. Participants who have cancer and have not been in remission for at least 5 years.
8. Participants with abnormal liver function tests (at Visit 1).
9. Pregnancy, breast-feeding or women intending to become pregnant during the course of the study.
10. Participants using Ziziphus spinosa or other herbal medicine with 4 weeks of Visit 1.

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)
Sealed opaque envelopes and numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
There are no previous randomised controlled trials of Ziziphus spinosa seeds alone for insomnia. Therefore a total of 12 people will be recruited based on convenience sampling. THis si a cross-over study and comparisons will be assessed from participants that have data from the end of the first treatment period and the end of the second treatment period using paired analysis. Change from baseline will also be assessed within groups. Chi-squared tests will be used to associations between categorical variables (age, gender, insomnia severity, insomnia type etc). Analysis of covariance (ANOVA) will be used for repeated measures using the General Liner Model. An intention-to-treat analysis will be applied.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 24077 0
3083 - Bundoora

Funding & Sponsors
Funding source category [1] 300693 0
University
Name [1] 300693 0
RMIT University SHBS Athena Swan Career Break Award
Address [1] 300693 0
RMIT University
PO BOX 71
Bundoora
VIC 3083
Country [1] 300693 0
Australia
Primary sponsor type
University
Name
RMIT University
Address
RMIT University
PO BOX 71
Bundoora
VIC 3083
Country
Australia
Secondary sponsor category [1] 300223 0
None
Name [1] 300223 0
Address [1] 300223 0
Country [1] 300223 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 301475 0
Royal Melbourne Institute of Technology Human Research Ethics Committee
Ethics committee address [1] 301475 0
RMIT University
PO BOX 71
Bundoora
VIC 3083
Ethics committee country [1] 301475 0
Australia
Date submitted for ethics approval [1] 301475 0
06/09/2018
Approval date [1] 301475 0
Ethics approval number [1] 301475 0

Summary
Brief summary
This is a randomised, placebo controlled cross-over study to assess the efficacy and safety of Ziziphus spinosa seeds in people with insomnia compared to placebo. This study aims to determine if Ziziphus spinosa seeds can improve sleep in people with insomnia, in terms of sleep quality, quantity, and associated daytime symptoms; and to determine its safety profile for insomnia. It is expected that Ziziphus spinosa seeds will alleviate some significant symptoms of insomnia and improve sleep quality, quantity, and associated daytime symptoms.The study integrates rigorous clinical trial design and research methodology and will guide the appropriate use of Chinese herbal medicine in clinical practice.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87142 0
Dr Johannah Shergis
Address 87142 0
RMIT University
PO BOX 71
Bundoora
VIC 3083
Country 87142 0
Australia
Phone 87142 0
+61 3 9925 6527
Fax 87142 0
Email 87142 0
johannah.shergis@rmit.edu.au
Contact person for public queries
Name 87143 0
Dr Johannah Shergis
Address 87143 0
RMIT University
PO BOX 71
Bundoora
VIC 3083
Country 87143 0
Australia
Phone 87143 0
+61 3 9925 6527
Fax 87143 0
Email 87143 0
johannah.shergis@rmit.edu.au
Contact person for scientific queries
Name 87144 0
Dr Johannah Shergis
Address 87144 0
RMIT University
PO BOX 71
Bundoora
VIC 3083
Country 87144 0
Australia
Phone 87144 0
+61 3 9925 6527
Fax 87144 0
Email 87144 0
johannah.shergis@rmit.edu.au

No data has been provided for results reporting
Summary results
Not applicable