Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000773831
Ethics application status
Approved
Date submitted
12/05/2021
Date registered
21/06/2021
Date last updated
13/01/2023
Date data sharing statement initially provided
21/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Light Therapy for Fatigue and Daytime Sleepiness in Multiple Sclerosis
Scientific title
The Feasibility and Preliminary Effects of Novel Light Therapy in Individuals with Neurological Disorders- Multiple Sclerosis
Secondary ID [1] 304012 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ENLighTIND-MS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 321631 0
Fatigue 321633 0
Daytime sleepiness 321634 0
Condition category
Condition code
Neurological 319372 319372 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will assess the effects of green-blue light therapy, delivered using Re-Timer light therapy glasses, on fatigue and daytime sleepiness in individuals living with multiple sclerosis. Participants will be asked to wear the Re-Timer glasses for 30 minutes each morning upon awakening for the duration of a four-week intervention. Re-Timer glasses deliver light at a maximum wavelength of 500nm (230 µW/cm2, 506 lux). Participants will be provided with a booklet which will contain simplified instructions on how to use the Re-Timer glasses. The instruction booklet will be developed by the study team based on manufacturer instructions and recommendations (presented in the Re-Timer user manual). Participants will be asked questions at the end of each week for the duration of the intervention period via text message or email to determine adherence to the intervention.

Following the four-week intervention period and follow-up testing, a washout period will be observed to monitor the duration of any potential effects.
Intervention code [1] 320322 0
Treatment: Devices
Comparator / control treatment
Comparative treatment: Sleep hygiene guidance

The control/comparator group will be an active control group. Sleep hygiene guidance will be disseminated to all participants in the study (i.e. both the green-blue light therapy group and the comparator group). Sleep hygiene guidelines will be provided in a booklet format and will contain advice on sleep and wake timing, daytime and night time habits and routines that can help to promote good sleep and aspects of the sleep environment that can be adapted for better sleep health, such as lighting, temperature and bedding. These guidelines will be collated into a study-specific booklet by the research team from various sources, including the National Sleep Foundation and the Australasian Sleep Association. All study participants will receive a phone call lasting up to 30 minutes (depending on participant questions) at the beginning of the intervention period to explain the sleep hygiene guidelines and provide advice on how they may best be able to implement the guidelines into their daily/nightly schedule. This phone call will be conducted by a researcher specialising in sleep. Participants will be asked questions at the end of each week for the duration of the intervention period via text message or email to determine adherence to the intervention.
Control group
Active

Outcomes
Primary outcome [1] 327230 0
Feasibility- participant recruitment rates as assessed by an audit of study records.
Timepoint [1] 327230 0
Recruitment rates will be assessed at the conclusion of the study.
Primary outcome [2] 327815 0
Feasibility- participant completion rates as assessed by an audit of study records.
Timepoint [2] 327815 0
Participant completion rates will be assessed at the conclusion of the study.
Primary outcome [3] 327816 0
Feasibility - program tolerance as assessed by a composite of the Brief Emotional Experience Scale, Brief Emotional Experience Scale-Physical and Depression Anxiety Stress Scale.
Timepoint [3] 327816 0
Program tolerance will be measured at the conclusion of the study.
Secondary outcome [1] 394308 0
Fatigue as measured using the Fatigue Severity Scale.
Timepoint [1] 394308 0
Fatigue will be measured at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [2] 395212 0
Sleep quality as measured using the Pittsburgh Sleep Quality Index.
Timepoint [2] 395212 0
Sleep quality will be measured at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [3] 395263 0
Daytime sleepiness as measured using the Epworth Sleepiness Scale.
Timepoint [3] 395263 0
Daytime sleepiness will be measured at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [4] 395266 0
Sleep environment as measured using the Sleep Environment Questionnaire.
Timepoint [4] 395266 0
Sleep environment will be measured at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [5] 395268 0
Sleep quality as measured using wrist-worn actigraphy.
Timepoint [5] 395268 0
Sleep quality will be measured each day for one week at baseline, following the four-week intervention and following the four-week washout period
Secondary outcome [6] 395269 0
A composite of daily sleep routines as measured using the Consensus Sleep Diary.
Timepoint [6] 395269 0
Daily sleep routines will be measured for one week each at baseline, following the four-week intervention and following the four-week washout period
Secondary outcome [7] 395272 0
Night time temperature exposure in the bedroom as measured using a HOBO pendant light and temperature sensor.
Timepoint [7] 395272 0
Night time temperature exposure will be measured at baseline, following the four-week intervention and following the four-week washout period
Secondary outcome [8] 395274 0
Work productivity as measured using the Work Productivity and Activity Impairment Specific Health Problem Questionnaire.
Timepoint [8] 395274 0
Work productivity will be measured at baseline, following the four-week intervention and following the four-week washout period
Secondary outcome [9] 395278 0
Emotional state as measured using the Depression, Anxiety, Stress Scale (DASS-21).
Timepoint [9] 395278 0
Emotional state will be measured at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [10] 395279 0
Emotional well-being as measured using the Brief Emotional Experiences Survey.
Timepoint [10] 395279 0
Emotional well-being will be measured at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [11] 395280 0
Physical well-being as measured using the Brief Emotional Experiences Survey-Physical.
Timepoint [11] 395280 0
Physical well-being will be measured at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [12] 395283 0
Exploration of genetic markers using saliva sampling techniques.
Timepoint [12] 395283 0
Saliva samples will be collected at baseline, following the four-week intervention and following the four-week washout period.
Secondary outcome [13] 395430 0
Temporal changes in fatigue as measured using the Fatigue Visual Analogue Scale.
Timepoint [13] 395430 0
Temporal changes in fatigue will be measured using the Fatigue Visual Analogue Scale.

Participants will be asked to complete the fatigue visual analogue scale at the end of each week throughout the intervention.
Secondary outcome [14] 395431 0
Temporal changes in emotional will be measured with the Brief Emotional Experiences Survey at the end of each week throughout the intervention.
Timepoint [14] 395431 0
Temporal changes in physical well-being will be measured with the Brief Emotional Experiences Survey-Physical at the end of each week throughout the intervention.
Secondary outcome [15] 396694 0
Primary outcome: Feasibility- adherence to the program as assessed by an audit of the study records.
Timepoint [15] 396694 0
Program adherence will be measured at the conclusion of the study.
Secondary outcome [16] 396695 0
Primary outcome: Feasibility- compliance with the prescribed program as assessed by an audit of the study records.
Timepoint [16] 396695 0
Compliance with the prescribed program will be measured at the conclusion of the study.
Secondary outcome [17] 396696 0
Sleep timing as measured using wrist-worn actigraphy.
Timepoint [17] 396696 0
Sleep timing will be measured each day for one week at baseline, following the four-week intervention and four-week washout period.
Secondary outcome [18] 396697 0
Night time light exposure in the bedroom as measured using a HOBO pendant light and temperature sensor.
Timepoint [18] 396697 0
Night time light exposure exposure will be measured each night for one week at baseline, following the four-week intervention and four-week washout period.
Secondary outcome [19] 406198 0
Patient-determined Disease Steps (PDDS)
Timepoint [19] 406198 0
The PDDS will be performed at baseline, following the four-week intervention and following the four-week washout period.

Eligibility
Key inclusion criteria
1) confirmed clinical diagnosis of multiple sclerosis using the revised McDonald criteria, and in the case of relapsing-remitting MS, clinically verified stable disease in the four weeks leading up to the study.
2) a score of equal to or greater than 4 on the Fatigue Severity Scale and/or a score of equal to or greater than 5 on the Pittsburgh Sleep Quality Index (indicative of self-perceived poor sleep quality) and/or a score of equal to or greater than 10 on the Epworth Sleepiness Scale (indicative of daytime somnolence),
3) between the ages of 18 and 65,
4) the capacity to speak reasonable English, understand verbal and written instructions and be able to complete tests and questionnaires without significant assistance,
5) be able to give informed consent to participate in the study in accordance with the ICH GCP guidelines before initiating any study related procedures.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) untreated hallucinations or psychosis,
2) current use of hypnosedative or illicit stimulant drugs,
3) use of antidepressants, unless the participant has been receiving a stable dose for at least four weeks,
4) visual abnormalities that may interfere with light therapy, including cataracts, narrow-angle glaucoma or blindness,
5) transmeridian travel or night shift work in the six weeks leading up to the study (or the intention to travel or undertake night shift during the study),
6) symptomatology of severe untreated depression (defined by a score of equal to or greater than 11 on the depression component of the DASS-21), and
7) pre-existing chronic fatigue syndrome, narcolepsy or sleep apnoea

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)
Participant allocation will be conducted via central randomisation by computer by the investigators delivering the intervention and will be concealed from investigators enrolling and administering testing procedures and performing data analyses.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be conducted using adaptive randomisation methods (minimisation) based on disease stage and severity of fatigue.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size estimates (n = 29 per group) were obtained based on a power calculation (a=.05 and power (1-ß)=90%) for the primary outcome (fatigue, using a previously published study [Sinclair et al, 2014]) and factoring in a drop-out rate of 25%.

Normality assumptions will be assessed using Shapiro-Wilk tests. Mixed model analysis of variance (ANOVA) will be used to determine between- and within-group changes for each outcome. Associations between outcomes will be determined using Pearson (for parametric data) and Spearman (for non-parametric data) correlations. Mediation/moderation analyses will be conducted to determine the factors influencing whether an individual is a responder or non-responder to the intervention. Minimal detectable changes will be determined throughout the trial to evaluate the clinical utility of the experimental treatments.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/02/2022
Actual
19/01/2022
Date of last participant enrolment
Anticipated
31/08/2023
Actual
Date of last data collection
Anticipated
29/12/2023
Actual
Sample size
Target
58
Accrual to date
28
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment postcode(s) [1] 33977 0
6027 - Joondalup

Funding & Sponsors
Funding source category [1] 308392 0
Charities/Societies/Foundations
Name [1] 308392 0
MSWA
Country [1] 308392 0
Australia
Primary sponsor type
University
Name
Edith Cowan University
Address
270 Joondalup Drive
Joondalup WA
6027
Country
Australia
Secondary sponsor category [1] 309222 0
None
Name [1] 309222 0
Address [1] 309222 0
Country [1] 309222 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308356 0
Edith Cowan University Human Research Ethics Committee
Ethics committee address [1] 308356 0
270 Joondalup Drive
Joondalup WA
6027
Ethics committee country [1] 308356 0
Australia
Date submitted for ethics approval [1] 308356 0
Approval date [1] 308356 0
27/03/2020
Ethics approval number [1] 308356 0
2020-01134

Summary
Brief summary
Fatigue and excessive daytime sleepiness are common complaints in individuals living with multiple sclerosis (MS). Fatigue and excessive daytime sleepiness are associated with the emergence and exacerbation of cognitive, motor and mood disturbances and over time lead to impaired rehabilitation outcomes, a decline in the capacity to perform daily activities and reduced quality of life. Treatment of fatigue and daytime somnolence in individuals with MS is therefore essential.

Over the last three decades a large body of evidence has accumulated noting the positive effects of non-pharmaceutical strategies for treating sleep and circadian rhythm disturbances in individuals with sleep disorders. Among these, sleep hygiene and light therapy have been shown to be efficacious for sleep and circadian rhythm disruption. Despite this large body of evidence, a relatively small number of studies have evaluated the therapeutic utility of sleep hygiene and light therapy for the treatment of fatigue and daytime sleepiness in individuals with MS. Preliminary evidence suggests that these strategies are feasible and effective in treating fatigue and daytime sleepiness in individuals with traumatic brain injury and Parkinson’s disease. However, there is a fundamental need to replicate these findings in individuals with other neurological conditions, including MS, using larger randomised controlled trials. Furthermore, there is a need to evaluate the synergistic effects of both therapeutic approaches for these populations.

The purpose of this study is to evaluate the feasibility and therapeutic effects of light therapy in combination with sleep hygiene, compared to sleep hygiene alone, in individuals with MS. It is hypothesised that both therapies will have positive effects on fatigue and daytime sleepiness, however, light therapy plus sleep hygiene will be more beneficial in reducing symptoms of fatigue and daytime sleepiness in individuals with MS than sleep hygiene alone.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110430 0
Dr Travis Cruickshank
Address 110430 0
School of Medical and Health Sciences
Edith Cowan University
270 Joondalup Drive
Joondalup WA 6027
Country 110430 0
Australia
Phone 110430 0
+61 08 6304 3416
Fax 110430 0
Email 110430 0
[email protected]
Contact person for public queries
Name 110431 0
Dr Travis Cruickshank
Address 110431 0
School of Medical and Health Sciences
Edith Cowan University
270 Joondalup Drive
Joondalup WA 6027
Country 110431 0
Australia
Phone 110431 0
+61 08 6304 3416
Fax 110431 0
Email 110431 0
[email protected]
Contact person for scientific queries
Name 110432 0
Dr Travis Cruickshank
Address 110432 0
School of Medical and Health Sciences
Edith Cowan University
270 Joondalup Drive
Joondalup WA 6027
Country 110432 0
Australia
Phone 110432 0
+61 08 6304 3416
Fax 110432 0
Email 110432 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified participant data may be shared upon reasonable request following completion of the study.
When will data be available (start and end dates)?
Data may be available beginning three months and ending five years following the main results publication.
Available to whom?
Researchers will need to submit an expression of interest to study investigators to access the data. If the proposal is deemed methodologically sound, access to the data will be granted.
Available for what types of analyses?
Data will be made available for the type of analysis outlined in the expression of interest/proposal document that is submitted to study investigators.
How or where can data be obtained?
Access to data will be subject to approval by the research team. Once approved, data will be shared via email correspondence with a member of the research team (please contact the Chief Investigator, Dr Travis Cruickshank, for further information at [email protected]).


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.