A novel transcranial photobiomodulation device to address motor signs of Parkinson's disease: a parallel randomised feasibility study.

Background: Parkinson's disease is a progressive neurological disease with limited treatment options. Animal models and a proof-of-concept case series have suggested that photobiomodulation may be an effective adjunct treatment for the symptoms of Parkinson's disease. The aim was to determine the safety and feasibility of transcranial photobiomodulation (tPBM) to reduce the motor signs of Parkinson's disease. Methods: In this double-blind, randomised, sham-controlled feasibility trial, patients (aged 59-85 years) with idiopathic Parkinson's disease were treated with a tPBM helmet for 12 weeks (72 treatments with either active or sham therapy; stage 1). Treatment was delivered in the participants' homes, monitored by internet video conferencing (Zoom). Stage 1 was followed by 12 weeks of no treatment for those on active therapy (active-to-no-treatment group), and 12 weeks of active treatment for those on sham (sham-to-active group), for participants who chose to continue (stage 2). The active helmet device delivered red and infrared light to the head for 24 min, 6 days per week. The primary endpoints were safety and motor signs, as assessed by a modified Movement Disorders Society revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III)-motor scale. This trial is registered with ANZCTR, ACTRN 12621001722886. Findings: Between Dec 6, 2021, and Aug 12, 2022, 20 participants were randomly allocated to each of the two groups (10 females plus 10 males per group). All participants in the active group and 18 in the sham group completed 12 weeks of treatment. 14 participants in the sham group chose to continue to active treatment and 12 completed the full 12 weeks of active treatment. Treatment was well tolerated and feasible to deliver, with only minor, temporary adverse events. Of the nine suspected adverse events that were identified, two minor reactions may have been attributable to the device in the sham-to-active group during the active treatment weeks of the trial. One participant experienced temporary leg weakness. A second participant reported decreased fine motor function in the right hand. Both participants continued the trial. The mean modified MDS-UPDRS-III scores for the sham-to-active group at baseline, after 12 weeks of sham treatment, and after 12 weeks of active treatment were 26.8 (sd 14.6), 20.4 (sd 12.8), and 12.2 (sd 8.9), respectively, and for the active-to-no-treatment group these values were 21.3 (sd 9.4), 16.5 (sd 9.4), and 15.3 (sd 10.8), respectively. There was no significant difference between groups at any assessment point. The mean difference between groups at baseline was 5.5 (95% confidence interval (CI) -2.4 to 13.4), after stage 1 was 3.9 (95% CI -3.5 to 11.3 and after stage 2 was -3.1 (95% CI 2.7 to -10.6). Interpretation: Our findings add to the evidence base to suggest that tPBM is a safe, tolerable, and feasible non-pharmaceutical adjunct therapy for Parkinson's disease. While future work is needed our results lay the foundations for an adequately powered randomised placebo-controlled clinical trial. Funding: SYMBYX Pty Ltd.

A Randomized Placebo-Controlled Study of a Transcranial Photobiomodulation Helmet in Parkinson's Disease: Post-Hoc Analysis of Motor Outcomes.

Emerging evidence is increasingly supporting the use of transcranial photobiomodulation (tPBM) to improve symptoms of neurodegenerative diseases, including Parkinson's disease (PD). The objective of this study was to analyse the safety and efficacy of tPBM for PD motor symptoms. The study was a triple blind, randomized placebo-controlled trial with 40 idiopathic PD patients receiving either active tPBM (635 nm plus 810 nm LEDs) or sham tPBM for 24 min per day (56.88J), six days per week, for 12 weeks. The primary outcome measures were treatment safety and a 37-item MDS-UPDRS-III (motor domain) assessed at baseline and 12 weeks. Individual MDS-UPDRS-III items were clustered into sub-score domains (facial, upper-limb, lower-limb, gait, and tremor). The treatment produced no safety concerns or adverse events, apart from occasional temporary and minor dizziness. There was no significant difference in total MDS-UPDRS-III scores between groups, presumably due to the placebo effect. Additional analyses demonstrated that facial and lower-limb sub-scores significantly improved with active treatment, while gait and lower-limb sub-scores significantly improved with sham treatment. Approximately 70% of participants responded to active treatment (≥5 decrease in MDS-UPDRS-III score) and improved in all sub-scores, while sham responders improved in lower-limb sub-scores only. tPBM appears to be a safe treatment and improved several PD motor symptoms in patients that responded to treatment. tPBM is proving to be increasingly attractive as a possible non-pharmaceutical adjunct therapy.

Protocol for randomized controlled trial to evaluate the safety and feasibility of a novel helmet to deliver transcranial light emitting diodes photobiomodulation therapy to patients with Parkinson's disease.

Introduction: Parkinson's disease (PD) is the second most common, progressive, and debilitating neurodegenerative disease associated with aging and the most common movement disorder. Photobiomodulation (PBM), the use of non-thermal light for therapeutic purposes using laser or light emitting diodes (LED) is an emerging non-invasive treatment for a diverse range of neurological conditions. The main objectives of this clinical trial are to investigate the feasibility, safety, tolerability, and efficacy of a novel transcranial LED helmet device (the "PDNeuro") in the alleviation of symptoms of PD. Methods and analysis: This is a 24-week, two-arm, triple-blinded randomized placebo-controlled clinical trial of a novel transcranial "PDNeuro" LED Helmet, comparing an active helmet to a sham helmet device. In a survey, 40 PD participants with Hoehn and Yahr Stage I-III during ON periods will be enrolled and randomly assigned into two groups. Both groups will be monitored weekly for the safety and tolerability of the "PDNeuro" LED Helmet. Clinical signs and symptoms assessed will include mobility, fine motor skills and cognition, with data collected at baseline, 12 weeks, and 24 weeks. Assessment tools include the TUG, UPDRS, and MoCA all validated for use in PD patients. Patient's adherence to the device usage and participant drop out will be monitored weekly. At 12 weeks both placebo and treatment groups will crossover and placebo participants offered the treatment. The main indicator for clinical efficacy of the "PDneuro" Helmet is evidence of sustained improvements in motor and non-motor symptoms obtained from participant self-reported changes, carer reporting of changes and objective reassessment by the investigators. The outcomes will assist in a future larger randomized trial design. Clinical Trial Registration: [https://www.anzctr.org.au], identifier [12621001722886].