Revitalize Cognition: Near Infrared Stimulation in Parkinson Patients

Not Applicable

Completed

Conditions: Parkinson Disease

Registration Number: NCT06688357

Lead Sponsor: University of Florida

Brief Summary: The overall goal of this pilot, proof of concept study is to test a novel, relatively low cost, low risk and potentially high impact intervention for cognitive and motor symptoms associated with idiopathic Parkinson Disease. The intervention involves transcranial delivery of near infrared (NIR) light, aka as photobiomodulation (PBM). This pilot randomized controlled trial will examine whether NIR stimulation influences cognitive, mood, and motor symptoms in Parkinson patients relative to a sham treated group. The goal is to determine effect sizes for a potentially larger study.

Aims 1-3 of this study (Older Adult Specific) is registered separately under NCT02582593

Detailed Description: There are few validated approaches for minimizing cognitive changes that frequently accompany Parkinson disease (PD). The goal of this study is to test a novel and potentially high impact brain stimulation approach for enhancing cognitive, mood, and motor symptoms in individuals with PD. This brain stimulation approach involves transcranial delivery of near infrared (NIR) light, which is painless and undetectable, and enhances brain metabolism. This NIR stimulation approach is also known as photobiomodulation (PMB).

The study builds on the following premises:

Mitochondrial dysfunction has been implicated in both familial and nonfamilial Parkinson disease.

NIR stimulation is a novel intervention for enhancing mitochondrial energy metabolism; Indeed, research in cellular and animal models suggests that application of light in red (630-700nm) and near infrared wavelengths (808-904nm) is neuroprotective and improves mitochondrial function by promoting increased production of intracellular adenosine triphosphate (ATP), important for cellular metabolism and oxygenation.

Findings of positive effects of NIR stimulation on motor and cognitive symptoms in animal models of PD, both rodent and macaques. In these animal studies, strong evidence supports neuroprotective and 'rescue' effects of NIR stimulation from MPTP-induced neurodegeneration, including preservation of locomotor activity and midbrain dopaminergic neurons. It is unclear whether similar beneficial effects might be afforded humans with idiopathic Parkinson disease (PD).

As such, the goal is to conduct a proof-of-concept randomized control pilot study to determine feasibility, acceptability and efficacy of a NIR stimulation protocol in individuals with Parkinson disease (PD). The intervention will involve six sessions over a 2-week period, in which active or sham stimulation is applied to the head using a delivery system that has been approved as a nonsignificant risk since 2003. The delivery system involves six MedX superluminous light emitting diode clusters positioned on the head in distinct configurations for a total of 40 minutes of stimulation. Dosing was based on a pilot study. The investigators plan to enroll 24 non-demented individuals with PD who will be randomized to active or sham groups. Cognitive, motor, and mood outcomes will be obtained before and after the intervention. An exploratory aim involves neuroimaging changes (1P MRS, resting state fMRI). Outcomes will be obtained during the off-dopamine medication state (i.e., standard overnight withdrawal from dopamine medications). The investigators hope to learn whether NIR stimulation has potential for influencing motor and cognitive symptoms in individuals with PD, with goal of determining effect sizes for a potentially larger randomized clinical trial.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Diagnosis of idiopathic Parkinson disease by movement disorder neurologist using UK Brain Bank criteria
Early-mid stage of disease severity
Willingness to undergo baseline and post-intervention 'off' their normal dopamine medications
Between 62 and 89 years of age
Able to provide informed consent and perform cognitive and mood measures on a computer
Willingness to be randomized to Sham or Real intervention
Can devote 2 weeks to the intervention, and additional time for pre and post testing
8th grade education and ability to read on 8th grade level based on scores on the Wechsler Test of Adult Reading (WTAR) or the Wide Range Achievement Test-IV (WRAT-IV); ability to see 14 pt. text
On stable doses of major medications for at least two months

Exclusion Criteria

History of brain abnormalities/ neurological disorders affecting cognition other than PD; No history of brain surgery
Evidence of potential dementia based on cognitive screening (e.g., scores < 5th %ile on the Montreal Cognitive Assessement (MoCA) or the Dementia Rating Scale-2 (DRS-2) based on appropriate age, education and sex norms.
Use of psychotics, sedatives or other medications with anticholinergic properties;
Unstable or uncontrolled medical conditions (e.g.,HIV, severe kidney disease)
Diagnosis of active cancer
Use of photosensitive medications within 15 days of intervention
Sensory loss (vision, hearing) or motor deficits that would preclude participation in the experimental cognitive tasks or neuropsychological assessment
Current or past history of major psychiatric disturbance including schizophrenia, or active psychosis, bipolar disorder, current major depressive episode, current alcohol or substance abuse or history thereof within the past six months. The investigators are not excluding individuals who are taking antidepressants or anti-anxiety medications, however, use of antidepressants and anxiolytics will be recorded and data will be analyzed in post-hoc analyses
Previous participation in a cognitive training study within the last six months

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
ARENA Spatial Navigation Memory Task-Learning Composite	Baseline and Post-Intervention (2 weeks)	ARENA is a task of spatial memory-navigation that has been linked to hippocampal function and is a human analogue to the Morris water maze, which has shown sensitivity to NIR stimulation in Alzheimer's transgenic mice. ARENA requires participants to learn and navigate to a hidden target location in a simulated environment. It involves use of a joystick over a series of 8 learning trials and one final probe trial. On each learning trial, the path length and time to reach the target are recorded. The Learning dependent variable is a composite score consisting of mean z-scores for path length and for time to reach the target (Learning Composite). A change score is computed by subtracting the baseline Learning Composite from the post-intervention Learning Composite z-score. Higher scores mean a better outcome.
Fluency Composite From NIH Examiner (Kramer et al., 2014).	Baseline and Post-Intervention (2 weeks)	The Fluency Composite is derived from the NIH Examiner, a computer-based battery of executive functioning tasks (Kramer et al., 2014). This composite was chosen due to known verbal fluency difficulties in individuals with Parkinson Disease. Verbal fluency tasks in the NIH Examiner include 2 trials of letter fluency and 2 trials of semantic fluency which are combined to yield a Fluency Composite that ranges from -3.0 to 3.0; higher scores correspond to better fluency performance. A change score is calculated by subtracting the baseline scores from the post-test scores. Greater positive change scores mean better outcome.
ARENA Spatial Navigation Memory Task - Total Composite	Baseline and Post-Intervention (2 weeks)	ARENA is a computer-based task of spatial memory-navigation that has been linked to hippocampal function and is a human analogue to the Morris water maze. ARENA consists of 9 learning trials and one final probe trial. On each learning trial, the path length and time to reach the target are recorded. On each probe trial, the percent time spent in the spatial quadrant where the target is located is recorded. The dependent variable is a total composite score consisting of mean z-scores for path length, time to reach the target, and %time in the target quadrant during the probe trial (Total Composite). A change score is computed by subtracting the baseline Total Composite z-score from the post-intervention Composite z scores. Higher scores mean better outcome.
Gait Stride Length Variability	Baseline and Post-Intervention (2 weeks)	Gait is assessed using the Primary Gait Screen (Schmidt et al., 2019) that requires participants to walk the length of an 8-meter pressure sensitive mat (Zeno Walkway, 120Hz, Zeno Metrics), turn around, and return to the beginning of the walkway. Gait variability during forward walking was selected because in PD, greater variability is associated with increased number of falls and is one of the most disabling symptoms in PD. For this outcome, variability in stride length is indexed by the individual's standard deviation (SD) of stride length measured in centimeters; higher SD scores indicate worse performance. A change score is calculated by subtracting baseline SD of stride length from the post-intervention scores. Negative change scores mean better performance, whereas positive change scores mean worse performance.

Secondary Outcome Measures

Name	Time	Method
Rey Auditory Verbal Learning Test (RAVLT)	Baseline and Post (2 weeks)	The RAVLT is a commonly used memory task in clinical settings. It is a 15-item word list learning task given over 5 trials followed by delayed recall of the list 20-30 minutes later. The major outcome is number of items freely recalled after the delay. Scores can range from 0 to 16 (maximum number of words), with higher score reflecting better performance. A change score is calculated by subtracting the baseline score from the post-intervention score. Higher difference scores indicate better performance due to intervention.
Negative Affect Scale From the Emotion Module of the NIH Toolbox	Baseline and Post-Intervention (2 weeks)	The Negative Affect scale is derived from the emotion module of the NIH Toolbox, a 12-22 minute self-report assessment that surveys current emotion health. The Negative Affect Scale is based on ratings of a series of emotion words. Questions comprise Likert-type items using computerized adaptive testing based on item response theory, resulting in a normed T score (mean of 50, SD of 10). The Negative Affect scale includes items pertaining to fear, anger, sadness. Scores below 40T indicate low levels of negative affect and scores above 60T indicate higher levels of negative affect. A difference score is computed by subtracting the baseline score from the post-intervention score.
Working Memory Composite From the NIH Examiner (Kramer et al., 2014)	Baseline and Post (2 weeks)	This Working Memory composite is derived from a computer-based battery of executive functioning tasks (NIH Examiner). This composite was chosen due to known working memory difficulties in individuals with Parkinson disease. The Working Memory composite consists of scores from the N-back task and a Dot Counting task, which are combined to yield a composite score that ranges from -3 to 3.0; higher scores correspond to better working memory. A change score is calculated by subtracting the baseline Working Memory Composite from the post-intervention Working Memory Composite.