Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000970741
Ethics application status
Approved
Date submitted
28/08/2013
Date registered
30/08/2013
Date last updated
12/02/2021
Date data sharing statement initially provided
12/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Melatonin and Cognitive-Behaviour Therapy for the treatment of insomnia in individuals with schizophrenia
Scientific title
For individuals with schizophrenia and insomnia, can melatonin and CBT improve sleep, symptoms, functioning and cognitive functions
Secondary ID [1] 282542 0
Nil
Universal Trial Number (UTN)
U1111-1143-2948
Trial acronym
SIPS (Sleep Intervention Program for Schizophrenia)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia
 289211 0
Insomnia 289962 0
Condition category
Condition code
Mental Health 289542 289542 0 0
Schizophrenia
Public Health 289543 289543 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This clinical trial will be conducted to assess the relative or combined efficacy of Melatonin (Circadin), and Cognitive Behavioural Therapy for Insomnia in Schizophrenia: CBT-I(S).

There will be four experimental treatment conditions:
Arm 1: CBT-I(s) and placebo
Arm 2: melatonin
Arm 3: CBT-I(S) and melatonin
Arm 4: placebo

Intervention details:

Arm 1: CBT-I(S) and Placebo: 4 weekly sessions of CBT-I(S), and placebo capsules (corn starch) – daily use for 4 weeks. All CBT-I(S) sessions will be administered to small groups of participants (4-5) by a psychologist. CBT-I(S) merges cognitive and behavioural therapies that address elements specifically found to maintain insomnia, such as poor sleep hygiene, dysfunctional beliefs and attitudes about sleep, rumination, and anxiety. Mainly education and discussion format. Total 4 sessions over 4 weeks (1 session a week for approx 2 hours).

Arm 2: melatonin: Exogenous slow-release melatonin (‘Circadin’) - total 4 mg of melatonin (in capsule) per person daily for 4 weeks

Arm 3: CBT-I(S) and melatonin: 4 weekly sessions of CBT-I(S), and daily use of exogenous melatonin capsules (Circadin) 4mg for 4 weeks. CBT-I(S) session as described in Arm 1.

Arm 4: placebo: Placebo capsules (corn starch) – daily use for 4 weeks

Treatment instructions for both melatonin and placebo conditions will remain identical. Participants will be told to ingest a daily dose of melatonin, or placebo, after a light meal two hours prior to bedtime for 4 weeks.

At Week 3, a face-to-face check-up visit will be required for all participants to conduct a pill count and check treatment adherence. At the end of the trial, any unused medication (melatonin or placebo) will be returned to Graylands Hospital Pharmacy, alongside an accountability form, and disposed of in accordance with policies at Graylands Hospital Pharmacy for clinical trials.
Intervention code [1] 287211 0
Treatment: Drugs
Intervention code [2] 287212 0
Behaviour
Comparator / control treatment
Placebo: corn starch capsule, made to look/weigh the same as the melatonin capsule to ensure double-blind. To match melatonin condition, participants will be asked to take the capsule daily for 4 weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 289636 0
Reduction in insomnia symptoms, based on Insomnia Severity Index
Timepoint [1] 289636 0
After each weekly session, and at the end of the trial (comparison of pre-treatment baseline data, with post-treatment data collected at week 5)
Primary outcome [2] 289637 0
Improvements in sleep - as measured with actigraphy and sleep diaries
Timepoint [2] 289637 0
At the end of the trial (comparison of pre-treatment baseline data, with post-treatment data collected at week 5)
Secondary outcome [1] 302920 0
Improvements in clinical symptoms, assessed with Brief Psychiatric Rating Scale (BPRS)
Timepoint [1] 302920 0
At the end of the trial (comparison of pre-treatment baseline data, with post-treatment data collected at week 5)
Secondary outcome [2] 302921 0
Improvements in cognitive performance on measures of attention (CPT-IP, Letter Cancellation task), learning and memory (Rey Auditory Verbal Learning Task), processing speed (Symbol Digit Modality Test, Token Motor Task, Letter Cancellation task), motor performance (Finger Tapping task), and executive functions (Verbal Fluency, Number Generation Task; Trails Making Test)
Timepoint [2] 302921 0
At the end of the trial (comparison of pre-treatment baseline data, with post-treatment data collected at week 5)
Secondary outcome [3] 302922 0
Improvements in functional health measured with the SF-36 Health Survey
Timepoint [3] 302922 0
At the end of the trial (comparison of pre-treatment baseline data, with post-treatment data collected at week 5)
Secondary outcome [4] 304350 0
Improvements in sleep hygiene practices and positive thinking, assessed with the Sleep Hygiene Index and Perseverative Thinking Questionnaire
Timepoint [4] 304350 0
At the end of the trial (comparison of pre-treatment baseline data, with post-treatment data collected at week 5)

Eligibility
Key inclusion criteria
1. Aged 25 to 50 years.
2. A diagnosis of schizophrenia or schizoaffective disorder
3. Length of illness 10-15 years
4. Currently in a clinically stable condition
5. Current insomnia symptoms, characterised by Sleep Onset Latency (SOL) more than 30 minutes, or waking up 3 or more times per night, with an ongoing duration of the sleep problem for at least one month.
6. Stable medication schedule and dosage for the past month
7. English as a first language
8. Using contraceptives (applicable to females only)
9. Confirmation of diagnosis and suitability for the study by the potential participant’s treating psychiatrist
10. Able to provide informed consent
Minimum age
25 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diagnosis or high indication of sleep-related breathing disorder (e.g. obstructive sleep apnoea), narcolepsy, nightmare disorder, periodic limb movement syndrome, or restless legs syndrome.
2. Suicidality.
3. Allergy to melatonin, corn starch, gelatine
4. BMI >35 (clinical obesity).
5. Co-morbid significant medical conditions (e.g. seizure disorder, traumatic brain injury, dementia, autoimmune disease, liver failure, or kidney failure).
6. Known hereditary problem of galactose intolerance, the LAPP lactase deficiency, or glucose-galactose malabsorption.
7. Pervasive developmental disorder or mental retardation, as defined by DSM-IV or DSM-V criteria.
8. Pregnant or breastfeeding (applicable to females only).

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 allocate participants to one of the four treatment conditions, there will be two levels of randomisation.

Allocation is not concealed for the first level of randomisation. At the first level of randomisation, each participant will be assigned an ID code by the principal investigator, and a randomised number system using a statistical randomiser will be used to determine whether participants receive CBT-I(S) or no CBT-I(S) treatment.
Because the CBT-I condition cannot be blinded, this randomisation will be conducted by the principal investigator. The ID codes will be used on all study materials to maintain anonymity.

Allocation is concealed for the second level of randomisation. Treatment condition will remain undisclosed to both the researchers and participants until cessation of the trial. To achieve double-blinding of melatonin/placebo, the trials pharmacist at Graylands Hospital (who has no knowledge of or contact with participants) will generate trial randomisation codes for the allocation of participants to treatment with melatonin or placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation method will be with statistical randomiser in computer software (like SPSS).
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
Factorial
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Participants will include 64 clinically stable individuals with chronic schizophrenia or schizo-affective disorder (aged 25 to 50) (recruitment target will be 80 participants anticipating 25% attrition rate)
Sample size was determined on the ability to detect a large effect between groups from baseline to post-treatment. Calculations were conducted using the G-Power program for repeated-measures ANOVA apriori sample size analysis, at an alpha error probability of 0.05. A sample size of 16 participants in each group (total number of 64) provided 90% power to detect an effect size of 0.50 amongst four groups. While Cortesi and colleagues (2012; the same design in autistic children) reported a very strong effect size between their combination and placebo group (effect size of 0.67), based on actigraphically recorded TST from baseline to 12 week assessment, we chose a more conservative effect size in light of Shamir et al.’s (2000) more modestly reported differences in actigraphically recorded TST between placebo and melatonin conditions in schizophrenia. Assuming a 25% dropout rate, our recruitment target will be 80 participants (20 participants per condition).

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
15/01/2014
Actual
4/03/2014
Date of last participant enrolment
Anticipated
15/01/2016
Actual
25/08/2015
Date of last data collection
Anticipated
Actual
7/10/2015
Sample size
Target
64
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 1460 0
Graylands Selby-Lemnos & Special Care Hospital - Mount Claremont
Recruitment postcode(s) [1] 7293 0
6010 - Mount Claremont

Funding & Sponsors
Funding source category [1] 287329 0
University
Name [1] 287329 0
University of Western Australia, Personal Research Funds (Flavie Waters, Vivian Chiu)
Country [1] 287329 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
Stirling Highway Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 286076 0
Hospital
Name [1] 286076 0
North Metro Mental Health
Address [1] 286076 0
Mailing address: Private Mail Bag 1, Claremont 6010, WA
Country [1] 286076 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289304 0
North Metropolitan Area Mental Health Services Human Research Ethics Committee (EC00273)
Ethics committee address [1] 289304 0
Ethics committee country [1] 289304 0
Australia
Date submitted for ethics approval [1] 289304 0
02/09/2013
Approval date [1] 289304 0
08/11/2013
Ethics approval number [1] 289304 0
Project (11_2013)

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

Contacts
Principal investigator
Name 40238 0
A/Prof Flavie Waters
Address 40238 0
The University of Western Australia, via Clinical Research Centre, Graylands Hospital, John XXIII Avenue, Shenton Park 6010, WA

Mailing addressing: Clinical Research Centre, Private Mail Bag 1, Claremont 6010, WA
Country 40238 0
Australia
Phone 40238 0
+61893476650
Fax 40238 0
Email 40238 0
[email protected]
Contact person for public queries
Name 40239 0
Flavie Waters
Address 40239 0
The University of Western Australia, via Clinical Research Centre, Graylands Hospital, John XXIII Avenue, Shenton Park, 6010, WA

Mailing addressing: Clinical Research Centre, Private Mail Bag 1, Claremont 6010, WA
Country 40239 0
Australia
Phone 40239 0
+61893476650
Fax 40239 0
Email 40239 0
[email protected]
Contact person for scientific queries
Name 40240 0
Flavie Waters
Address 40240 0
The University of Western Australia, via Clinical Research Centre, Graylands Hospital, John XXIII Avenue, Shenton Park, 6010, WA

Mailing addressing: Clinical Research Centre, Private Mail Bag 1, Claremont 6010, WA
Country 40240 0
Australia
Phone 40240 0
+61893476650
Fax 40240 0
Email 40240 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
Ethics approval had not been sought for individual participant data to be shared, as our application specified that data would be analysed as a group, and data sharing outside of WA Health would require extra ethics amendments.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10645Study protocol  [email protected]
10646Informed consent form  [email protected]
10647Ethical approval  [email protected]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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