Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001722886
Ethics application status
Approved
Date submitted
12/11/2021
Date registered
16/12/2021
Date last updated
27/10/2023
Date data sharing statement initially provided
16/12/2021
Date results information initially provided
16/03/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluating the safety and feasibility of the application of transcranial photobiomodulation therapy for the clinical signs and quality of life of Parkinson's disease patients
Scientific title
Evaluating the safety and efficacy of a transcranial photobiomodulation therapy device on the clinical signs and symptoms, and quality of life of Parkinson's disease patients
Secondary ID [1] 305782 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease 324289 0
Condition category
Condition code
Neurological 321780 321780 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the treatment group will receive photobiomodulation (infra-red light) intervention via an external transcranial device that is worn on the head. Participants will receive photobiomodulation intervention to 20 separate locations on the head 6 times per week for a total of 12 treatment weeks. Each treatment session will last for 24 minutes with a total energy absorption of 154.5 joules. Participants in the placebo group will receive the same intervention protocol as the treatment group delivered using a structurally identical sham transcranial device that delivers no infra-red light. Participants will be contacted by Zoom at weekly intervals for the first 4 weeks and at fortnightly intervals thereafter to monitor their adherence to the intervention and the safety of the intervention.
At the conclusion of the 12 weeks of active treatment, participants will receive no treatment for 12 weeks. At the conclusion of 12 weeks of sham treatment, participants will be offered 12 weeks of active treatment
Intervention code [1] 322180 0
Treatment: Devices
Comparator / control treatment
Participants who are randomized to the placebo group will receive the identical intervention protocol delivered by a structurally identical sham transcranial device that delivers no infra red light.
Control group
Placebo

Outcomes
Primary outcome [1] 329537 0
The modified Unified Parkinson's Disease Rating Scale (UPDRS) Motor (III) assessments consisting of the following: Speech; Facial Expression; Finger Tapping; Hand Movements; Pronation-supination Movements of Hands; Toe Tapping; Leg Agility; Arising from Chair; Gait; Freezing of Gait; Posture; Global Spontaneity of Movement (Body Bradykinesia); Postural Tremor of the Hands; Kinetic Tremor of the Hands; Rest Tremor Amplitude; Constancy of Rest Tremor; Dyskinesia Impact on Part III Ratings; Hoen and Yahr Stage.
Timepoint [1] 329537 0
1. Baseline (before intervention).
2. 12-weeks (primary timepoint)
3. 24-weeks
Primary outcome [2] 329737 0
Safety.
Safety was assessed by interview with the participants and care-givers (via internet video conference), based on participant (and/or care-giver) observation of adverse events. Any change in participant signs or symptoms was recorded and reviewed by a suspected adverse event committee consisting of two (blinded) researchers (a neurologist and an expert light therapist) and an independent neurologist.
Timepoint [2] 329737 0
weekly to week 4 then fortnightly for the duration of the study (minimum 24 weeks)
Secondary outcome [1] 402907 0
Cognitive function using remote Montreal Cognitive Assessment (MoCA)
Timepoint [1] 402907 0
1. Baseline (before intervention)
2. 12-weeks
3. 24-weeks
Secondary outcome [2] 403631 0
Smell-test.
Timepoint [2] 403631 0
1. Baseline (before intervention)
2. 12-weeks
3. 24-weeks
Secondary outcome [3] 403632 0
functional mobility using timed up and go test
Timepoint [3] 403632 0
1. Baseline (before intervention)
2. 12-weeks
3. 24-weeks
Secondary outcome [4] 403633 0
Parkinson's disease questionnaire (PDQ) 39
Timepoint [4] 403633 0
1. Baseline (before intervention)
2. 12-weeks
3. 24-weeks
Secondary outcome [5] 403634 0
Parkinson's Sleep Scale
Timepoint [5] 403634 0
1. Baseline (before intervention)
2. 12-weeks
3. 24-weeks
Secondary outcome [6] 403635 0
Micrographia test assessed by digitising a written sentence and measuring letter perimeter and area using Image J software
Timepoint [6] 403635 0
1. Baseline (before intervention)
2. 12-weeks
3. 24-weeks
Secondary outcome [7] 428266 0
carer-givers diary
The care-givers diary will be used to assess quality of life changes of the participant as well as any other information that the care-giver considers important (such as ease of use of the device, any change in signs and symptoms including suspected adverse events..
Change was made prior to first enrolment.
Timepoint [7] 428266 0
Secondary outcome [8] 428267 0
carer-givers diary
The care-givers diary will be used to assess quality of life changes of the participant as well as any other information that the care-giver considers important (such as ease of use of the device, any change in signs and symptoms including suspected adverse events..
Change was made prior to first enrolment.
Timepoint [8] 428267 0
fortnightly for the duration of the study (minimum 24 weeks)

Eligibility
Key inclusion criteria
Females and males diagnosed with Idiopathic Parkinson's disease (by UK Brain Bank Criteria) with Modified Hoen & Yahr staging of I - III during ON periods, and with 3 or more weeks of stable anti-Parkinson's disease medication.
Sufficient space at home (around 9 m2) to be able to perform motor assessments; Stable and sufficiently fast home-based internet connection for uninterrupted video calls and video conferencing; Knowledge (self or carer) of using a phone and/or tablet applications on either IOS or Android platforms
Minimum age
60 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants with the following will be excluded from the study, if they: are incapable of self-care; have cognitive impairment with a MoCa score of <24; history of significant psychotic episode(s) within the last 12-months; history of suicidal ideation or attempted suicide within the last 12-months; take potentially photosensitising medication, especially imipramine, hypericum, phenothiazine, lithium, chloroquine, hydrochlorothiazide, or tetracycline; have a history of structural brain disease, active epilepsy, stroke or acute illness, factors affecting gait performance and stance such as severe joint disease, orthopaedic injuries, weakness, peripheral neuropathy with proprioceptive deficits, severe peripheral vascular occlusive disease, severe musculoskeletal disorders, uncorrected vision, vestibular problems or other severe conditions (such as those that preclude the use of photobiomodulation therapy, that places the patient at risk during evaluation of their Parkinson's disease, or interferes with the evaluation of their Parkinson's disease); have cardiac disease; are currently participating other trials regarding the treatment of Parkinson's disease, such as advanced therapies (including Duodopa, Apomorphine, Deep Brain Stimulation).

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)
Central randomisation by MATLAB computer software
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (computerised sequence generation)
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
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
ANOVA
independent t-test and Kruskal-Wallis test

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
6/12/2021
Date of last participant enrolment
Anticipated
17/12/2021
Actual
23/02/2022
Date of last data collection
Anticipated
19/06/2022
Actual
12/08/2022
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment postcode(s) [1] 35950 0
2064 - Artarmon
Recruitment postcode(s) [2] 35951 0
2076 - Wahroonga

Funding & Sponsors
Funding source category [1] 310138 0
Commercial sector/Industry
Name [1] 310138 0
SYMBYX Biome
Country [1] 310138 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
SYMBYX Biome
Address
2/50 Yeo Street, Neutral Bay, Sydney, NSW 2089
Country
Australia
Secondary sponsor category [1] 311214 0
Charities/Societies/Foundations
Name [1] 311214 0
San Foundation
Address [1] 311214 0
185 Fox Valley Rd, Wahroonga, NSW, 2077
Country [1] 311214 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309827 0
Adventist HealthCare Limited
Ethics committee address [1] 309827 0
Level 4 Clifford Tower, Administration Corridor, Room 10, 185 Fox Valley Road, Wahroonga, NSW 2076
Ethics committee country [1] 309827 0
Australia
Date submitted for ethics approval [1] 309827 0
26/10/2021
Approval date [1] 309827 0
02/11/2021
Ethics approval number [1] 309827 0
2019-032

Summary
Brief summary
The main aim of this study is to investigate the safety and feasibility of transcranial photobiomodulation intervention, using infrared LEDs, for patients diagnosed with Parkinson's disease. It is hypothesised that the application of transcranial photobiomodulation might produce clinically meaningful improvements in the quality of life for people living with Parkinson's disease. This feasibility study will inform on a larger, adequately powered randomised placebo-controlled clinical trial.
Trial website
Trial related presentations / publications
Public notes
The following references describe the clinically relevant background information that underlines the study protocol.
Calabresi P, Castrioto A, Di Filippo M, et al. New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson’s disease. Lancet Neurol. 2013;12(8):811-821.
Calabresi P, Ghiglieri V, Mazzocchetti P, et al. Levodopa-induced plasticity: a double-edged sword in Parkinson’s disease? Philos Trans R Soc B-Biological Sci. 2015;370(1672):1-14.
Chung H, Dai T, Sharma SK, et al. The nuts and bolts of Low-level Laser (Light) Therapy. Ann Biomed Eng. 2012;40(2):516-533.
Darlot F, Moro C, El Massri N, et al. Near-infrared light is neuroprotective in a monkey model of Parkinson’s disease. Ann Neurol. 2016;79(1):59-75.
Deloitte Access Economics 2015 Living with Parkinson's Disease: An updated economic analysis 2014. Accessed at: http://www.parkinsons.org.au/deloitte-report_copy.
Ferrazzoli D, Carter A, Ustun FS, et al. Dopamine replacement therapy, learning and reward prediction in Parkinson’s Disease: Implications for rehabilitation. Front Behav Neurosci. 2016;10:121.
Fuhrer H, Kupsch A, Hälbig TD, et al. Levodopa inhibits habit-learning in Parkinson’s disease. J Neural Transm. 2014;121(2):147-151.
Hamblin, M. R. Shining light on the head: photobiomodulation for brain disorders. BBA Clinical 6(2016): 113-124.
Johnstone DM, el Massri N, Moro C, et al. Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism – An abscopal neuroprotective effect. Neuroscience. 2014;274:93-101.
Johnstone D M, Moro C, Stone J, et al. Turning on lights to stop neurodegeneration: The potential of near infrared light therapy in Alzheimer's and Parkinson's Disease. Front Neurosci, 2015,9:500.
Moro C, Massri N El, Torres N, et al. Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice. J Neurosurg. 2014;120(3):670-683.
Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003; 41 (5): 582 – 592.
Pellegrini C, Antonioli L, Colucci R, et al Gastric motor dysfunctions in Parkinson’s disease: Current pre-clinical evidence. Parkinsonism Rel Disord. 2015; 21 (12):1407-1414.
Saltmarche AE, Naeser MA, Ho KF, et al. Significant improvement in cognition in mild to moderately severe dementia cases treated with transcranial plus intranasal photobiomodulation: Case series report. Photomed Laser Surg. 2017;10.
Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell. 2016;167:1469-80. e12.
Scheperjans F, Aho V, Pereira PAB, Koskinen K, Paulin L, Pekkonen E, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Movement Disorders. 2015;30:350-8.
Shaw V E, Peoples C, Spana S, et al. Patterns of cell activity in the subthalamic region associated with the neuroprotective action of Near-Infrared light treatment in MPTP-treated mice. Parkinson’s Dis, 2012;296875.
Stone J, Mitrofanis J The helmet experiment: an observation of the mechanism of action of LED-sourced infrared light. World Association for Laser Therapy WALT2012 biennial congress, Gold Coast, September 27-30.
Tomlinson CL, Patel S, Meek C, et al. Physiotherapy versus placebo or no intervention in Parkinson’s disease. Cochrane Database Syst Rev. 2013;(9):CD002817.
Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson’s Disease. JAMA Neurol. 2017;74(4):411.
Zesiewicz TA, Baker MJ, Wahba M, Hauser RA. Autonomic nervous system dysfunction in Parkinson’s disease. Current Treatment Options in Neurology. 2003;5:149-60.

Contacts
Principal investigator
Name 115522 0
Dr Ann Liebert
Address 115522 0
Sydney Adventist Hospital, 185 Fox Valley Road, Wahroonga, NSW 2076
Country 115522 0
Australia
Phone 115522 0
+61 409311887
Fax 115522 0
Email 115522 0
[email protected]
Contact person for public queries
Name 115523 0
Dr Ann Liebert
Address 115523 0
Sydney Adventist Hospital, 185 Fox Valley Road, Wahroonga, NSW 2076
Country 115523 0
Australia
Phone 115523 0
+61409311887
Fax 115523 0
Email 115523 0
[email protected]
Contact person for scientific queries
Name 115524 0
Dr Vincent Pang
Address 115524 0
Sydney Adventist Hospital, 185 Fox Valley Road, Wahroonga, NSW 2076
Country 115524 0
Australia
Phone 115524 0
+61 466965412
Fax 115524 0
Email 115524 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
Commercial trial


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14072Study protocol    383116-(Uploaded-01-10-2023-14-42-31)-Study-related document.docx
14074Ethical approval    383116-(Uploaded-01-10-2023-15-42-38)-Study-related document.pdf
14075Informed consent form    383116-(Uploaded-12-11-2021-14-14-58)-Study-related document.docx
20717OtherTrial extension and additional treatment assessments request and HREC acknowledgement with no further actions required   383116-(Uploaded-23-09-2023-22-34-50)-Study-related document.pdf
20718Other    383116-(Uploaded-01-10-2023-15-10-56)-Study-related document.pdf
20766Other    23/04/2023 McGee, C.; Liebert, A.; Bicknell, B.; ... [More Details] 383116-(Uploaded-01-10-2023-15-16-01)-Journal results publication.pdf



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes 23/04/2023 McGee, C.; Liebert, A.; Bicknell, B.; ... [More Details] 383116-(Uploaded-01-10-2023-15-16-01)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA novel transcranial photobiomodulation device to address motor signs of Parkinson's disease: a parallel randomised feasibility study.2023https://dx.doi.org/10.1016/j.eclinm.2023.102338
EmbaseA Randomized Placebo-Controlled Study of a Transcranial Photobiomodulation Helmet in Parkinson's Disease: Post-Hoc Analysis of Motor Outcomes.2023https://dx.doi.org/10.3390/jcm12082846
N.B. These documents automatically identified may not have been verified by the study sponsor.