Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000734965
Ethics application status
Approved
Date submitted
13/07/2011
Date registered
13/07/2011
Date last updated
20/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Melatonin for Sleep Disturbance Following Acquired Brain Injury
Scientific title
Efficacy of Melatonin for Sleep Disturbance Following Acquired Brain Injury
Secondary ID [1] 262424 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The primary health condition to be investigated is sleep disturbance in individuals who have sustained an acquired brain injury. 268115 0
A secondary health condition is to investigate depression and anxiety. 268116 0
Condition category
Condition code
Neurological 268258 268258 0 0
Other neurological disorders
Mental Health 268259 268259 0 0
Depression
Mental Health 268260 268260 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Circadin melatonin 2mg prolonged release tablet is be taken orally after food and 1-2 hours prior to going to bed. Participants will be required to consume each of the respective treatments for a total of 8 weeks. Treatment intervention will commence at week 3 after the baseline run in period. As this a crossover study, the active melatonin treatment may be administered at either the first or second treatment intervention with each intervention 4 weeks in duration. The frist treatment intervention will commence at week 3 and end at week 6, with the second treatment intervention commencing at week 7 and finishing at week 10.
Intervention code [1] 266797 0
Treatment: Drugs
Comparator / control treatment
The control formulation matched active treatment for appearance and size consisting of Mannitol (106mg), Acacia (11mg) and Pure icing sugar (106mg). Both treatments were encapsulated in identical two-piece gelatin capsules and dispensed in identical containers, containing 30 capsules.
Both the active and placebo treatment was taken orally and 1-2 hours prior to habitual bedtime. Participants were directed to consume treatment for a total of eight weeks. Treatment intervention will commence at week 3 after the baseline run-in period. As this a crossover study, the placebo treatment may be administered at either the first or second treatment intervention with each intervention period four weeks in duration. The first treatment intervention will commence at week 3 and will end at week 6, with the second treatment intervention commencing at week 7 and finishing at week 10.
Control group
Placebo

Outcomes
Primary outcome [1] 268985 0
Sleep onset latency
Timepoint [1] 268985 0
Mean sleep onset latency (minutes) will be measured continuously throughout the trial and over the 10 week period via Actigraphy. Sleep onset latency will be averaged over the baseline period and after each intervention period, respectively.
Primary outcome [2] 297319 0
Sleep quality: Sleep quality will be determined by global scores from the Pittsburgh sleep quality index (PSQI) questionnaire. The PSQI requires participants to subjectively rate their sleep quality in the previous month and will be used to determine treatment efficacy.
Timepoint [2] 297319 0
Sleep quality will be assessed pre and post baseline, and at the end of each treatment period. Consistent with other measures, sleep quality will be first assessed at baseline (week 0). The second takes place at the end of the baseline run-in period (week 2). The third at the end of treatment one (Week 6). The fourth at the end of treatment two (week 10).
Secondary outcome [1] 276753 0
Depression and Anxiety will be assessed with the use of paper and pen Hospital Anxiety and Depression Scale (HADS).
Timepoint [1] 276753 0
Depression and Anxiety will be assessed at four time points. The first takes place on their baseline assessment (week 0). The second takes place at the end of the baseline run-in period (week 2). The third at the end of treatment one (Week 6). The fourth at the end of treatment two (week 10).
Secondary outcome [2] 276754 0
General health and well being will be assessed with the use of a papper and pen questionnaire namely the SF-36 Health Related Quality of Life Questionnaire (SF-36).
Timepoint [2] 276754 0
General health and Well being will be assessed at four time points. The first takes place on their baseline assessment (week 0). The second takes place at the end of the baseline run-in period (week 2). The third at the end of treatment one (Week 6). The fourth at the end of treatment two (week 10).
Secondary outcome [3] 320715 0
Mean sleep efficiency (%) determined by actigraphy.
Timepoint [3] 320715 0
Mean sleep efficiency (%): Sleep efficiency will be collected during baseline and throughout each treatment period. Sleep efficiency will be averaged over the baseline period and after each intervention period, respectively.
Secondary outcome [4] 320716 0
Daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS)
Timepoint [4] 320716 0
ESS scores will be collected pre and post baseline and at the end of each treatment intervention, respectively. Consistent with other measures, ESS scores will be first assessed at baseline (week 0). The second takes place at the end of the baseline run-in period (week 2). The third at the end of treatment one (Week 6). The fourth at the end of treatment two (week 10).

Eligibility
Key inclusion criteria
-Individuals with acquired brain injury (ABI), such as a traumatic brain injury (TBI) or stroke will be eligible to participate in the study;
-Outpatients not currently hospitalized;
-Able to understand and converse in English;
-Adequate cognitive and physical ability to complete questionnaires;
-Adequate visual acuity determined by the participants ability to read the questionnaires;
-TBI Patients with mild to severe TBI who have sustained blunt head trauma with loss of consciousness, as determined by an initial Glasgow Coma Scale of 3-15 OR a period of post-traumatic amnesia;
-Stroke patients with either Hemorrhagic or Ischemic infarctions.
-ABI patients with reported sleep difficulties as determined by a Pittsburgh sleep quality index greater or equal to a score of 8.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Pittsburgh sleep quality index less than 8;
-History of other neurological problems prior to ABI;
-Have traveled across more than 1 time zone in the preceding 3 months;
-Have worked night shift in the preceding 3 months;
-History of sleep disturbance prior to head trauma which required treatment;
-History of Chronic fatigue requiring treatment prior to head trauma;
-BMI greater than 30;
-Requiring surgery during participation in the trial;
-Current or previous history of illicit drug usage
-Women who are breast feeding
-Women currently pregnant or trying to conceive;
-Currently taking psychotropic medication which includes benzodiazepines or hypnotics;
-Currently taking Psycho stimulants;
-Currently consuming complimentary medicines to treat sleep disturbance.

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)
Rehabilitation physicians and allied health staff will be responsible for approaching and informing ABI participants with sleep disturbance of the study. All participants will need to seek approval from their treating rehabilitation physician in order to participate in the study. Suitable candidates will be referred to a research assistance to determine study eligibility. Individuals meeting preliminary eligibility will be referred for a sleep physician consultation to further determine eligibility. Individuals meeting eligibility criteria will be encouraged to discuss participation with family, friends and other doctors not involved in the study before consenting.
The rehabilitation physician will be responsible for writing the treatment scripts (i.e., melatonin and placebo), but is blinded to treatment. Treatment randomization will be computer generated and recorded by the pharmacist not involved or associated with the study, with randomization sealed in opaque envelopes. Each envelope will indicate the order of treatment and the pharmacist not associated with the study will allocate treatment accordingly.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization was conducted by a researcher independent of the study, not involved with recruitment, testing or analysis. Block randomization was used (block size of 4) and six possible balanced permutations for assignment to the two conditions were each assigned an integer from one to six. Treatment conditions were assigned and sealed in an envelope ("M" for Melatonin first and "P" Placebo first). Participant codes were sequentially allocated as participants enrolled and treatments were dispensed by a pharmacist not affiliated with the study. Participants were randomized to receive melatonin or placebo treatment first at the end of the baseline period.
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 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2011
Actual
9/03/2012
Date of last participant enrolment
Anticipated
Actual
5/08/2016
Date of last data collection
Anticipated
Actual
16/11/2016
Sample size
Target
80
Accrual to date
Final
41
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 2665 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 7533 0
Epworth Richmond - Richmond
Recruitment postcode(s) [1] 15358 0
3121 - Richmond East

Funding & Sponsors
Funding source category [1] 267267 0
Government body
Name [1] 267267 0
NHMRC
Country [1] 267267 0
Australia
Primary sponsor type
University
Name
Monash University
Address
School of Psychological Sciences,
Monash University
18 Innovation Walk
Clayton Campus, Clayton VIC 3800
Australia
Country
Australia
Secondary sponsor category [1] 266327 0
Hospital
Name [1] 266327 0
Epworth HealthCare
Address [1] 266327 0
Epworth Corporate,
89 Bridge Road,
Richmond, Victoria,
Australia, 3121.
Country [1] 266327 0
Australia
Secondary sponsor category [2] 266492 0
None
Name [2] 266492 0
Address [2] 266492 0
Country [2] 266492 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269286 0
Epworth Healthcare Human Research Ethics Committee
Ethics committee address [1] 269286 0
Pelaco Building One
Ground Floor
21-31 Goodwood Street,
Richmond,
VIC 3121
Ethics committee country [1] 269286 0
Australia
Date submitted for ethics approval [1] 269286 0
01/06/2011
Approval date [1] 269286 0
25/06/2011
Ethics approval number [1] 269286 0
52111
Ethics committee name [2] 269412 0
Monash University Human Research Ethics Committee
Ethics committee address [2] 269412 0
Monash Research Office
First Floor,
Building 3e,
Clayton Campus,
Monash University,
VIC 3800
Ethics committee country [2] 269412 0
Australia
Date submitted for ethics approval [2] 269412 0
22/06/2011
Approval date [2] 269412 0
Ethics approval number [2] 269412 0
2011001061
Ethics committee name [3] 291233 0
Austin Health Human Research Ethics Commitee
Ethics committee address [3] 291233 0
Austin Health Human Research Ethics Commitee
145 Studley Road
PO Box 5555 Heidelberg
Victoria, Australia, 3084
Ethics committee country [3] 291233 0
Australia
Date submitted for ethics approval [3] 291233 0
31/01/2013
Approval date [3] 291233 0
21/10/2013
Ethics approval number [3] 291233 0
HREC/13/Austin/7

Summary
Brief summary
Sleep disturbance occurs in a significant proportion of the Acquired Brain Injury (ABI) population. Traumatic Brain Injury, a type of ABI, has been associated with reduced sleep quality, more night-time awakenings and longer sleep onset latency's. Recent research has shown that TBI patients have significantly lower endogenous concentrations of melatonin in the evening as compared to healthy controls. Melatonin is a naturally occurring hormone in the body which is intricately involved in the regulation of sleep and more importantly with the timing of sleep. Specifically, recent work has shown that this reduced concentration of melatonin was related to reduced rapid eye movement sleep and that these patients had more arousals during the evening. In light of recent work which provides evidence that a prolonged release melatonin formula is efficacious in treating age-related insomnia in individuals who also have decreased bodily concentrations of melatonin, it is hypothesized that melatonin will reduce the time taken to sleep and will improve sleep quality in ABI patients. The current study will implement a randomized, placebo-controlled crossover study with the aim of recruiting 80 participants. ABI patients who report sleep disturbance post injury will be eligible to participate. As this is a crossover design every participant will receive both the placebo and active melatonin treatments. If melatonin therapy is successful in reducing latency to sleep and improved sleep quality this could substantially improve the quality of life of individuals with ABI. As melatonin is a naturally occurring hormone relatively devoid of side-effects, its use to treat sleep disturbance could be implemented into clinical practice.
Trial website
nil
Trial related presentations / publications
nil
Public notes

Contacts
Principal investigator
Name 32761 0
Prof Jennie Ponsford
Address 32761 0
School of Psychological Sciences,
18 Innovation Walk,
Monash University,
Clayton, Vic., 3800
Country 32761 0
Australia
Phone 32761 0
+61 3 9905 3058
Fax 32761 0
Email 32761 0
[email protected]
Contact person for public queries
Name 16008 0
Dr Miss Natalie Ann Grima
Address 16008 0
Cognitive Neurology Unit,
Beth Israel Deaconess Medical Center (BIDMC)
300 Brookline Avenue, Boston 02215, United States of America.
Country 16008 0
United States of America
Phone 16008 0
+1 617 543 4899
Fax 16008 0
Email 16008 0
[email protected]
Contact person for scientific queries
Name 6936 0
Prof Jennie Ponsford
Address 6936 0
School of Psychological Sciences,
18 Innovation Walk,
Monash University,
Clayton, Vic., 3800
Country 6936 0
Australia
Phone 6936 0
+61 3 9905 3058
Fax 6936 0
+61 3 9905 3948
Email 6936 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbasePoorer sleep quality predicts melatonin response in patients with traumatic brain injury: Findings from a randomized controlled trial.2021https://dx.doi.org/10.5664/jcsm.9234
EmbaseCircadian Melatonin Rhythm Following Traumatic Brain Injury.2016https://dx.doi.org/10.1177/1545968316650279
N.B. These documents automatically identified may not have been verified by the study sponsor.