In a recent study published in eClinicalMedicine, researchers evaluate whether transcranial photobiomodulation (tPBM) is a safe and feasible treatment option for reducing the motor signs of Parkinson's disease (PD), a neurological disease.
Study: A novel transcranial photobiomodulation device to address motor signs of Parkinson's disease: a parallel randomised feasibility study. Image Credit: PopTika/Shutterstock.com
Several pre-clinical and proof-of-concept case studies have shown the effectiveness of photobiomodulation (PBM) in PD cases. In rodent models of PD, it alleviated the clinical signs of PD and was neuroprotective and neuro-regenerative.
Likewise, in small-scale proof-of-concept case studies, transcranial PBM (tPBM) was beneficial when administered using an extracranial helmet. However, the effectiveness of its use on the head alone is still unclear.
About the study
In the present double-blinded, sham- and placebo-controlled randomized feasibility trial, researchers used a novel transcranial light-emitting diode (LED) helmet to administer tPBM as an adjunctive PD therapy.
Amid the coronavirus disease 2019 (COVID-19)-induced pandemic, they ran this study remotely in all recruited participants' homes in Australia. They were aged 59–85 years and had idiopathic PD. They received 72 treatments with active or sham therapies in Stage 1 over a duration of 12 weeks.
The team randomly assigned participants to either the sham or the active group by a blinded researcher who was not involved in participant contact, training, assessment, or data analysis.
A caregiver contacted participants at least every two weeks via Internet video conferencing (Zoom) to monitor safety and compliance and answer their queries about the fitting of the helmet device, its usage, or any side effects (if any). They also instructed active group participants to apply tPBM therapy consistently at the same time of day, if possible.
The appearance and operation of the active tPBM and the sham helmet were identical, except the latter did not produce light. The active helmet emitted red and infrared (IR) light over the head for 24 minutes (12 minutes of red and IR each), six days a week for 12 weeks (a total of 72 treatments).
Participants received these devices by post, and a trial technical advisor (unblinded to the treatments) taught participants how to fit and operate them.
After 72 treatments, the participants were unblinded for stage two of the study, wherein they offered 12 weeks of active treatment to the sham group (sham-to-active group), and treatment for the active group was ceased (active-to-no-treatment group).
The primary endpoints were motor signs of PD and device safety. For the motor signs, they used a modified Movement Disorders Society revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III). At the same time, they relied on manual assessments by a trial technical advisor during weekly virtual meetings to monitor safety.
In the absence of any data to determine the power of the study, they checked data for errors, normality, and the equality of variance of the residuals by visual inspection.
Further, they conducted t-tests to investigate the difference in MDS-UPDRS-III scores for all study groups at baseline and after stages one and two.
There were ten males and ten females in the active and sham groups, i.e., 20 participants in each group and 40 in the trial completed between December 6, 2021, and August 12, 2022.
All 20 participants in the active group and 18 in the sham group completed treatment, showing compliance in stage 1 was excellent.
When offered to receive active treatment, 14 sham group participants chose active treatment, and 12 even completed it for the whole duration, demonstrating it was feasible to deliver and was well-tolerated.
There were fewer (n=9) side effects, which were also minor and transient and reversed after a few weeks with treatment cessation.
Of the nine adverse events, two minor reactions occurred due to the device. One participant experienced transient leg weakness, and another reported reduced fine motor function in the right hand, and both continued the trial.
The average MDS-UPDRS-III scores for the sham-to-active and the active-to-no-treatment groups at baseline and after 12 weeks of sham and active treatment were 26.8, 20.4, 12.2, 21.3, 16.5, and 15.3, respectively.
The intergroup differences were insignificant at all assessment points, with an average difference between groups at baseline and after stages one and two of 5.5, 3.9, and −3.1 [95% confidence interval (CI)]. However, there was individual variation in response to tPBM and sham.
The disruption in treatment ranged from three days to eight weeks due to COVID-19 and logistics issues.
Yet, participants with disrupted treatment continued till all 72 treatments and even showed improvements in modified MDS-UPDRS-III scores over the 24 weeks of treatment.
Overall, tPBM emerged as a safe and feasible treatment to address motor signs of PD. Accordingly, all responders to active tPBM treatment showed significant improvement in five modified MDS-UPDRS-III sub-scores versus one sub-score for sham treatment.
Interestingly, placebo effects due to dopamine release led to a positive response to the sham helmet at 12 weeks, indistinguishable from active tPBM treatment.
Even these individuals showed further improvements upon receiving active treatment post-switch, suggesting a positive signal to tPBM above placebo. In addition, some participants in the active group continued to improve, indicating the stability of the tPBM treatment.
The exact mechanism of action of tPBM is unclear. Perhaps it enhances glymphatic drainage from the brain or light stimulation of the vagus nerve and the putative endorestiform nucleus in humans, unlike in animal models where it is neuroprotective.
Both mechanisms likely depend on the placement of the LEDs, i.e., below the posterior base of the skull.
Thus, the researchers emphasize the need for a larger, adequately powered, randomized crossover trial to extend earlier published evidence showing the safety and feasibility of tPBM as a non-pharmaceutical adjunct therapy for PD.