ANZCTR - Registration

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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]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Traumatic brain injury

Condition category

Condition code

Injuries and Accidents

Other injuries and accidents

Neurological

Other neurological disorders

Stroke

Haemorrhagic

Stroke

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]

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]

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]

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]

Daytime sleepiness, as measured by the Epworth Sleepiness Scale (ESS).

Timepoint [1]

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]

Sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI).

Timepoint [2]

Secondary outcome [3]

Psychomotor vigilance, as measured by the Psychomotor Vigilance Task (PVT), a short computer task used to measure sustained attention and reaction time

Timepoint [3]

Secondary outcome [4]

Mood, including the presence of states of anxiety and depression, as measured by the Hospital Anxiety and Depression Scale (HADS).

Timepoint [4]

Secondary outcome [5]

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]

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]

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]

Secondary outcome [7]

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]

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]

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]

Secondary outcome [9]

Insomnia, as measured by the Insomnia Severity Index (ISI).

Timepoint [9]

Secondary outcome [10]

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]

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]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Epworth Richmond - Richmond

Recruitment postcode(s) [1]

3121 - Richmond

Funding & Sponsors

Funding source category [1]

University

Name [1]

Monash University

Address [1]

Monash University
Wellington Rd
Clayton
VIC, 3800

Country [1]

Australia

Funding source category [2]

Other Collaborative groups

Name [2]

Monash-Epworth Rehabilitation Research Centre (MERRC)

Address [2]

Monash-Epworth Rehabilitation Research Centre (MERRC)
Ground Floor
185-187 Hoddle Street
Richmond, VIC, 3121

Country [2]

Australia

Primary sponsor type

Hospital

Name

Epworth HealthCare

Address

Epworth HealthCare
89 Bridge Rd
Richmond VIC, 3121

Country

Australia

Secondary sponsor category [1]

University

Name [1]

Monash University

Address [1]

Monash University
Wellington Rd
Clayton
VIC, 3800

Country [1]

Australia

Secondary sponsor category [2]

Charities/Societies/Foundations

Name [2]

Summer Foundation

Address [2]

PO Box 208
Blackburn VIC 3130

Country [2]

Australia

Secondary sponsor category [3]

University

Name [3]

Monash University

Address [3]

School of Psychological Sciences
Level 5, 18 Innovation Walk
Monash University
Clayton VIC 3800

Country [3]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Epworth HealthCare Human Research Ethics Committee

Ethics committee address [1]

Epworth HealthCare HREC
Ground Floor, Pelaco Building
21-31 Goodwood Street
Richmond Vic 3121

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/02/2017

Approval date [1]

03/05/2017

Ethics approval number [1]

EH2016-164

Ethics committee name [2]

Monash University Human Research Ethics Committee

Ethics committee address [2]

Monash University HREC
Wellington Rd, Clayton
VIC, 3800

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

09/05/2017

Approval date [2]

18/05/2017

Ethics approval number [2]

9246

Ethics committee name [3]

Monash Health Human Research Ethics Committe

Ethics committee address [3]

Research Support Services Monash Health
Level 2, I Block
Monash Medical Centre 246 Clayton Road
Clayton Victoria 3168

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

20/03/2019

Approval date [3]

20/03/2019

Ethics approval number [3]

RES-19-0000-194E

Summary

Brief summary

Fatigue is the most common and persistent complaint following a traumatic brain injury (Sinclair, 2012). It has been reported in patients who have experienced TBI across the spectrum of injury severity (Mathias & Alvaro, 2012) and is present in both the early and later stages of recovery (Baumann, Werth, Stocker, Ludwig, & Bassetti, 2007; Cantor, Bushnik, & Cicerone, 2012; Kempf, Werth, & Kaiser, 2010). Despite this, there are currently no effective treatments for posttraumatic brain injury fatigue (PTBIF). However, findings from a recent pilot trial suggest that light therapy may reduce PTBIF, as well as daytime sleepiness (Sinclair et al., 2014). The study found reductions in fatigue and daytime sleepiness following blue light treatment, in addition to a nonsignificant trend towards reduced depression, which suggest that light therapy may be an effective treatment for fatigue and sleepiness following TBI. However this therapy required the person with TBI to sit in front of a light box for 45 minutes in the morning. As such it places considerable demand on the user. As a consequence for many individuals it does not represent a longterm solution to the problem. This project aims to develop, implement and evaluate the efficacy of an in-home light therapy treatment for individuals experiencing post-traumatic brain injury fatigue (PTBIF). 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. 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 approximately 5.5 months, with six assessment points. Multiple measures will be taken at each of the assessment points. The study will recruit participants from the Epworth hospital who have sustained a mild, moderate or severe TBI and who are self-reporting significant fatigue. A sample size of 34 is proposed. Participants order of exposure to the light conditions will be randomised. The placebo condition will constitute a sham condition, and all participants will be blinded to the treatment conditions. The study will also entail a health economics analysis to assess the cost effectiveness of the intervention, as well as an examination of factors associated with response to the intervention.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Jennie Ponsford

Address

Monash-Epworth Rehabilitation Research Centre (MERRC)
Ground Floor
185-187 Hoddle Street
Richmond, VIC, 3121

Country

Australia

Phone

+61 3 9426 8923

Fax

[email protected]

Contact person for public queries

Name

Prof Jennie Ponsford

Address

Monash-Epworth Rehabilitation Research Centre (MERRC)
Ground Floor
185-187 Hoddle Street
Richmond, VIC, 3121

Country

Australia

Phone

+61 3 9426 8923

Fax

[email protected]

Contact person for scientific queries

Name

Prof Jennie Ponsford

Address

Monash-Epworth Rehabilitation Research Centre (MERRC)
Ground Floor
185-187 Hoddle Street
Richmond, VIC, 3121

Country

Australia

Phone

+61 3 9426 8923

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

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Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Development of a Home-Based Light Therapy for Fatigue Following Traumatic Brain Injury: Two Case Studies.	2021	https://dx.doi.org/10.3389/fneur.2021.651498

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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