Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000866303
Ethics application status
Approved
Date submitted
6/06/2017
Date registered
13/06/2017
Date last updated
15/09/2020
Date data sharing statement initially provided
5/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
In-home light therapy for fatigue following traumatic brain injury: A pilot randomized controlled trial
Scientific title
In-home light therapy for fatigue following traumatic brain injury: A pilot randomized controlled trial
Secondary ID [1] 292016 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic brain injury 303403 0
Condition category
Condition code
Injuries and Accidents 302816 302816 0 0
Other injuries and accidents
Neurological 303027 303027 0 0
Other neurological disorders
Stroke 311614 311614 0 0
Haemorrhagic
Stroke 311615 311615 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This project aims to develop, implement and evaluate the efficacy of an in-home light therapy treatment for individuals experiencing post-traumatic brain injury (PTBIF) and post-stroke fatigue. The study will be a pilot randomized controlled trial evaluating the impact of in-home lighting on subjective fatigue, as well as daytime sleepiness, sleep quality, psychomotor vigilance, mood, activity levels and quality of life. The study will employ a crossover design and thus all participants will be exposed to both lighting conditions (the active light condition, consisting of bright predominantly short wavelength light) and a second lighting condition that constitutes a placebo condition. Each will be 8 weeks in duration. Primary and secondary outcome variables will be measured at four weekly intervals: baseline, midway and end of each intervention and one month follow up, resulting in a protocol of 5.5 months, with six assessment points. Multiple measures will be taken at each of the assessment points. There will be no wash-out period between conditions as the carrover effects of the light are considered to be negligible. The main mechanism through which the light therapy is proposed to work is through the direct alerting or claiming effect of light. These patients do not have substantial circadian misalignment and therefore the light is not intended to correct and maintain a circadian phase problem, which would then make a ‘carry-over’ effect relevant over several subsequent days. The direct effects of light on alertness are immediate. When the light is changed to be less alerting, or switch off, there is a ‘half-life’ of about ~2 hours during which the alerting effects are maintained (for a wake example, see Rahman et al., Sleep 2014; for a sleep example, see Chellappa et al., J Sleep Res 2013). This duration of response (several hours) is not sufficient to require a wash-out between conditions that last for weeks, or to prompt concerns about any carry-over effects, as any influence will be gone by wake time.

The longitudinal nature of the study does not allow for formal tracking of patient compliance but we will be able to detect light exposure patterns through the wrist-borne activity monitor, including changes in light spectrum. Regarding dose, we will measure the light levels emitted by the lights in situ for both lighting conditions using a standard measurement approach in terms of distance and direction from the light sources. It is unrealistic and not standard practice to purport to measure actual ‘dose’ received (and even then, corneal exposure does not match retinal exposure): One can only describe the light environment in detail, which we will do, and therefore quantify the minimum and maximum corneal exposure in a space.

Device Description:
The HealthE Genesis lamp is a tunable and programmable LED lamp developed by the Lighting Science Group Corporation (LSGC). The primary function of the lamp is to deliver a biologically-optimised spectrum of light for every time of the day. It aims to promote alertness, energy and focus during the day and healthy and restful sleep in the evening. It does this by giving off a high concentration of blue-enriched light during waking hours and warmer temperature light during the evening. The HealthE Genesis Lamp has an accompanying iOS application from which you can regulate the spectrum setting of the light. The lamps also have onboard sensors to monitor local air quality.

Method of use:
The lamps can be powered by standard power source and configured using the Genesis App on iOS.

Mode of action and application:
These lamps will be used as a bedside lamp for participants in the research study, as well as being placed in rooms that do not have sufficient ceiling lighting. The lamps in the experimental condition of this study will be programmed so that they produce blue-enriched high-intensity white light with a high correlated colour temperature (CCT) of approximately 5000-6500K in the morning or ideally all day if they do not have access to daylight. In the evening, for as long as possible before bed, gradual dimming and blue-depletion of the light will occur. Thus, low CCT light will be used (less than 2700K).
Lamps will also be utilised in the placebo condition, however these will be programmed to reflect normal lighting conditions, and will not change in colour temperature across the course of the day/evening.

Device Description:
Standard commercially available light bulbs will be used in this study. The lighting will involve blue-enriched high-intensity white light with a high correlated colour temperature (CCT) of approximately 5000- 6500K during the day. In the evening, gradual dimming and blue- depletion of the light will occur (less than 2700K). Light bulbs of this colour temperature have been chosen due to the positive effects found following blue light treatment in a traumatic brain injury population, which include reducing fatigue and daytime sleepiness (Sinclair, Ponsford, Taffe, Lockley, & Rajaratnam, 2014).

Mode of action and application:
Possible lighting options in each participant’s house will be assessed prior to the commencement of the study to enable researchers to install light bulbs and lamps in appropriate places. Light bulbs will also be chosen based on the type of roof fixtures an individual has in their home (eg. some may have screw in light bulbs or bayonet fittings). These may vary between participants so the exact light bulb and its specifications will vary across participants, as not all fixtures will allow the same light bulbs. However an endeavour will be made by researchers to ensure that between participants, the spectrum and intensity of lighting is as similar as possible, within the specifications detailed above. The light bulbs for the roof lighting will be sourced from a local hardware store, such as Bunnings, following an assessment of the lighting set up and fixtures within participants homes. An electrician will be responsible for fitting lighting in participants’ houses due to OHS considerations. However it should be noted that the intended lighting is standard commercially available light bulbs for the residential home. The tailored lighting will remain installed for the duration of the active light condition of the study. Participants' normal house lighting will be re-installed for the placebo condition of the study. Researchers will work with participants to establish the appropriate timing of these applications during the active light condition.

Device Description:
Philips Respironics has a range of commercially available Actiwatches. Several different actiwatch models may be used with participants in this study including the Actiwatch 2 Activity monitor, Actiwatch Spectrum PLUS and the Actiwatch Spectrum PRO. They will all produce identical activity data. The use of different models is largely due to the availability of different watches in our research lab. The Phillips Actiwatch is a small, wrist-worn actigraph that measures motion. It looks and feels like a wristwatch.

Mode of action and application:
Participants will be required to wear the Actiwatch on their non-dominant wrist for the
duration of the study (day and night), including the 2-4 week baseline period. Internal memory and programming allows Actiwatch to keep data for long periods of time. The watches can also record periods of light. The Actiwatch will measure participants' sleep-wake schedule, activity levels and light exposure to determine any impact of the two light conditions. This device is only being used as a monitoring device and is not an investigational product in regard to this project.
Intervention code [1] 298149 0
Treatment: Devices
Comparator / control treatment
The placebo condition will constitute a sham condition, where "normal" lighting for participant is installed. "Normal" lighting will constitute a participant's original house lighting. All participants will be blinded to the treatment conditions. There may be some minimal differences in the illuminance of the lighting (the active light condition may look somewhat brighter), however no information will be provided to participants about the lighting conditions and the expected effect of the lighting. The placebo condition duration will be 8 weeks.
Control group
Active

Outcomes
Primary outcome [1] 302200 0
The primary outcome measure of fatigue will be measured using the Fatigue Severity Scale (FSS). Individuals will be considered responders if they demonstrate clinically significant changes in the primary outcome measure of fatigue.
Timepoint [1] 302200 0
Fatigue will be measured using the FSS at the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [1] 335567 0
Daytime sleepiness, as measured by the Epworth Sleepiness Scale (ESS).
Timepoint [1] 335567 0
At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [2] 335568 0
Sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI).
Timepoint [2] 335568 0
At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [3] 335569 0
Psychomotor vigilance, as measured by the Psychomotor Vigilance Task (PVT), a short computer task used to measure sustained attention and reaction time
Timepoint [3] 335569 0
At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [4] 335570 0
Mood, including the presence of states of anxiety and depression, as measured by the Hospital Anxiety and Depression Scale (HADS).
Timepoint [4] 335570 0
At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [5] 335571 0
Activity levels. Participants will wear actigraphy watches in order to monitor their activity during the study. Participants will wear Phillips Actiwatches (Phillips Respironics, Oregon, United States of America).

Activity levels will also be measured using a self-made activity questionnaire, which will be used to calculate the number of minutes spent on activity, rest and sleep in time blocks across the course of the day. Activity encompasses physical and mental activity (eg. doing chores, working on the computer), rest encompasses when the individual is giving their body a break (eg. lying down, taking a bath, listening to music) and sleep includes any periods of napping throughout the day.
Timepoint [5] 335571 0
The actigraphy watches and activity questionnaire will be used everyday by participants, however these will be assessed as an aggregate across the 6 time points: at the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study.
Secondary outcome [6] 335572 0
Quality of life, as measured by the Participation Objective Participation Subjective (POPS), a 26-item measure of participation in the home and community, and the impact different activities have on the user’s satisfaction with life (Brown et al., 2004).
Timepoint [6] 335572 0
At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [7] 335573 0
The cost of the intervention will also be assessed. A health economics questionnaire will be devised or sourced in collaboration with a health economist. This will include information about frequency of visits to health services such as GP, rehabilitation physician, disability services, sleep physician or psychologist, mental health service and so forth. This will be disseminated to participants to keep for the duration of the study, and for them to fill out when they attend a health service. They should log the date of visit, out-of-pocket cost, reason for attending, service type, and whether the reason for the appointment was accident-related.

The cost across the two study conditions (placebo and active condition) will be compared.
Timepoint [7] 335573 0
The participants will use the health economics questionnaire when needed throughout the course of the study. However aggregate data across the two study conditions will be assessed, resulting in two assessment points.
Secondary outcome [8] 335574 0
State levels of fatigue, as measured by the Brief Fatigue Inventory (BFI). The BFI is being used as an additional measure of fatigue as it captures fatigue in the last 24 hours and represents more of a “state-like” fatigue.
Timepoint [8] 335574 0
At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [9] 335575 0
Insomnia, as measured by the Insomnia Severity Index (ISI).
Timepoint [9] 335575 0
At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [10] 335576 0
A sleep diary will be used to track participants’ sleep habits, including sleep time, estimated time to fall asleep, awakenings, wake after sleep onset (WASO), wake time, estimated sleep duration, naps taken during the day, and rating of sleep quality. Sleep quality is rated on a 10 point likert scale, where 1 represents worst quality and 10 represents best quality sleep. This is to track whether there are any changes in participants’ sleep characteristics across the course of the intervention. A sleep diary will be assessed in combination with actigraphy data. The sleep diary has been sourced from the self-made resources at the Be Active Sleep Eat Facility (BASE) which forms part of Monash University.
Timepoint [10] 335576 0
The sleep diary will be completed daily throughout the study period by all participants. At the end of the 2-4 week baseline, at mid (4 weeks) and end of each treatment period (8 weeks), and at one month follow up, following the completion of the study. This results in 6 assessment points.
Secondary outcome [11] 335577 0
Illness severity will be measured by the Clinical Global Impression Scale (CGIS), a 3-item clinician-rated measure of illness severity (CGIS), global improvement or change (CGIC) and therapeutic response (Guy, 2000). This will be rated by the study physician.
Timepoint [11] 335577 0
This will be administered by an independent physician at two time points in the study in order to make a clinical evaluation of ‘change’, at the end of the two study lighting conditions. This will be compared to a baseline assessment of the patient’s condition undertaken by the physician.

Eligibility
Key inclusion criteria
Inclusion criteria for the study includes presence of mild, moderate or severe TBI, as ascertained by scores on the Glasgow Coma Scale (GCS) and duration of post-traumatic amnesia (PTA), and self-reported significant fatigue (Fatigue Severity Scale greater than or equal to 4). Participants injury should have occurred at least three months prior, and they must have been discharged from the hospital.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include any comorbid psychiatric disorders requiring hospitalization. Depressive symptoms are a secondary outcome, which will be assessed in both conditions of the light intervention. The use of antidepressants will be permitted provided a stable dosage is maintained across the course of the study. Additional exclusion criteria include the presence of another medical illness accounting for fatigue, including other neurological disorders, pre-injury sleep disorders or chronic fatigue syndrome, transmeridian travel within the preceding six weeks, current use of prescribed and over the counter sleep medications and inability to give informed consent as assessed by the participant’s treating neuropsychologist.

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)
Randomisation schedules will be generated by a research fellow, independent of both the study and data analysis, who will notify the therapist of the participant’s treatment condition.

Allocation will involve contacting the holder of the allocation schedule who will be at the central administration site: The Monash-Epworth Rehabilitation Research Centre (MERRC).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The study will employ a 2x2 cross-over design and thus all participants will be exposed to both lighting conditions (the active light condition, consisting of bright predominantly short wavelength light) and a second lighting condition that constitutes a placebo condition.

The 34 participants will be randomly assigned to either the AB or the BA sequence. All participants will be exposed to both conditions. After baseline, assessment randomisation will occur. A stratified randomisation will be adopted using a random permuted blocks within strata algorithm, stratified according to baseline fatigue to ensure levels are matched across conditions. Randomisation schedules will be generated by a research fellow, independent of both the study and data analysis, who will notify the therapist of the participant’s treatment condition.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Participants
Given the scale of the intervention rate of recruitment in a previous light therapy study, a modest sample size of 34 is proposed. Thirty participants in a between-subjects trial was sufficient to demonstrate treatment effects (large effect size) on the same measures as those proposed in the current study (Sinclair et al., 2014). A power analysis was undertaken using G*Power (Faul, Erdfelder, Lang, & Buchner, 2007), with power (1-ß) set at 0.80, with a level of .05 as recommended by Cohen (1988). The power to detect a medium effect size (dz = 0.50) was determined to be 0.82. The sample size required for adequate power for this analysis (within subjects) was N = 34.

Study Analyses
Treatment effect analyses will be performed using SAS v. 9.4 (SAS Institute Inc., Cary, NC, USA), and the remaining data analyses will be undertaken using IBM SPSS Statistics v. 23 (SPSS Inc., Chicago, IL, USA). An alpha level of .05 will be used for all statistical analyses.
Following standard best practice (e.g., Matthews, 2006), the cross-over design will be analyzed using pairs of measures with an independent samples t-test, following initial graphical analysis. As discussed previously, a carryover effect of treatment is not applicable in regards to this particular setting. Examination of changes or trajectory of measures such as the Fatigue Severity Score will be looked at graphically, and employing statistical methods appropriate for longitudinal data (Willett & Singer, 2003), mindful of the limited initial sample size.
Furthermore, analyses will be undertaken to assess the cost-effectiveness of the intervention, in relation to the primary outcome (fatigue). These analyses will be undertaken with the guidance of a health economist, and are thus still in the stage of being formulated.
Finally, a series of independent measures t-tests will be undertaken to examine whether there are significant differences in responders vs. non-responders, on a number of variables including: injury severity, individual differences in light sensitivity (phototype), chronotype, baseline psychiatric state, and baseline levels of fatigue and sleep disturbance. Individuals will be considered responders if they demonstrate significant changes in the primary outcome measure of fatigue in the active condition compared to the placebo condition.
Further to this, a series of linear multiple regressions will assess if scores on self-report measures of fatigue can significantly predict quality of life at each of the time points of the study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/06/2017
Actual
5/10/2017
Date of last participant enrolment
Anticipated
27/05/2021
Actual
Date of last data collection
Anticipated
30/12/2021
Actual
Sample size
Target
34
Accrual to date
24
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8239 0
Epworth Richmond - Richmond
Recruitment postcode(s) [1] 16298 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 296540 0
University
Name [1] 296540 0
Monash University
Country [1] 296540 0
Australia
Funding source category [2] 296646 0
Other Collaborative groups
Name [2] 296646 0
Monash-Epworth Rehabilitation Research Centre (MERRC)
Country [2] 296646 0
Australia
Primary sponsor type
Hospital
Name
Epworth HealthCare
Address
Epworth HealthCare
89 Bridge Rd
Richmond VIC, 3121
Country
Australia
Secondary sponsor category [1] 295496 0
University
Name [1] 295496 0
Monash University
Address [1] 295496 0
Monash University
Wellington Rd
Clayton
VIC, 3800
Country [1] 295496 0
Australia
Secondary sponsor category [2] 302925 0
Charities/Societies/Foundations
Name [2] 302925 0
Summer Foundation
Address [2] 302925 0
PO Box 208
Blackburn VIC 3130
Country [2] 302925 0
Australia
Secondary sponsor category [3] 302926 0
University
Name [3] 302926 0
Monash University
Address [3] 302926 0
School of Psychological Sciences
Level 5, 18 Innovation Walk
Monash University
Clayton VIC 3800
Country [3] 302926 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297762 0
Epworth HealthCare Human Research Ethics Committee
Ethics committee address [1] 297762 0
Ethics committee country [1] 297762 0
Australia
Date submitted for ethics approval [1] 297762 0
15/02/2017
Approval date [1] 297762 0
03/05/2017
Ethics approval number [1] 297762 0
EH2016-164
Ethics committee name [2] 297873 0
Monash University Human Research Ethics Committee
Ethics committee address [2] 297873 0
Ethics committee country [2] 297873 0
Australia
Date submitted for ethics approval [2] 297873 0
09/05/2017
Approval date [2] 297873 0
18/05/2017
Ethics approval number [2] 297873 0
9246
Ethics committee name [3] 303522 0
Monash Health Human Research Ethics Committe
Ethics committee address [3] 303522 0
Ethics committee country [3] 303522 0
Australia
Date submitted for ethics approval [3] 303522 0
20/03/2019
Approval date [3] 303522 0
20/03/2019
Ethics approval number [3] 303522 0
RES-19-0000-194E

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

Contacts
Principal investigator
Name 75034 0
Prof Jennie Ponsford
Address 75034 0
Monash-Epworth Rehabilitation Research Centre (MERRC)
Ground Floor
185-187 Hoddle Street
Richmond, VIC, 3121
Country 75034 0
Australia
Phone 75034 0
+61 3 9426 8923
Fax 75034 0
Email 75034 0
[email protected]
Contact person for public queries
Name 75035 0
Jennie Ponsford
Address 75035 0
Monash-Epworth Rehabilitation Research Centre (MERRC)
Ground Floor
185-187 Hoddle Street
Richmond, VIC, 3121
Country 75035 0
Australia
Phone 75035 0
+61 3 9426 8923
Fax 75035 0
Email 75035 0
[email protected]
Contact person for scientific queries
Name 75036 0
Jennie Ponsford
Address 75036 0
Monash-Epworth Rehabilitation Research Centre (MERRC)
Ground Floor
185-187 Hoddle Street
Richmond, VIC, 3121
Country 75036 0
Australia
Phone 75036 0
+61 3 9426 8923
Fax 75036 0
Email 75036 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
Only group data will be available.


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
EmbaseDevelopment of a Home-Based Light Therapy for Fatigue Following Traumatic Brain Injury: Two Case Studies.2021https://dx.doi.org/10.3389/fneur.2021.651498
N.B. These documents automatically identified may not have been verified by the study sponsor.