Clinical trial NCT06442033: Genetics and Aerobic Exercise to Slow Parkinson's Disease Trial
Official title: Genetics and Aerobic Exercise to Slow Parkinson's Disease (GEARS) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Parkinson Disease
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2024-06-04
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Single Group
Primary purpose: TREATMENT

Brief summary: The proposed multi-site, Genetics and Aerobic Exercise to Slow PD (GEARS) Trial will, for the first time, determine the interplay between genetics and exercise in altering PD progression. In sum, 200 PD patients will be recruited from the Cleveland and Salt Lake City metro areas to participate in the Pedaling for Parkinson's (PFP) community-based exercise program. Participants will exercise at community-based sites 3x/week for 12 months. All participants will undergo genotyping using an array that includes the genome backbone and common risk variants associated to increase risk for multiple neurological disorders including PD.

Detailed description: A long-standing unmet need in the treatment of Parkinson's disease (PD) is the identification of a disease-modifying intervention (e.g. pharmaceutical, surgical or behavioral). A growing body of evidence indicates that high-intensity aerobic exercise, when delivered in a highly supervised, well-controlled laboratory setting, improves PD symptomology. Two fundamental gaps remain related to the widespread utilization of exercise to slow PD: 1) are community-based exercise programs effective in altering disease progression and 2) what is the role of genetics in modulating the disease altering effects of high-intensity aerobic exercise? Our underlying hypothesis is that high-intensity, community-based exercise slows disease progression in PD and does so more effectively in individuals with a lower genetic/biological burden. Genetic burden for PD will be determined through the calculation of a PD polygenic risk score (PRS).

Total study duration is \~12.5 months to accommodate data collection sessions and enrollment in PFP class. The study consists of five in-person assessments at the Cleveland Clinic or the University of Utah: informed consent, enrollment (On- and Off-medication separated by at least 24 hrs), 6 months (Off-medication), and 12 months (Off-medication). Asking participants to withhold medication for Off-state examinations imposes a burden, but the Off-state (12 hours off meds) will increase insight into the direct effect of exercise on PD and provides more reliable, less confounded time comparisons. Antiparkinsonian medication will be reconciled at Baseline, 6- and 12-month timepoints. Outcome metrics are provided in Table 1. Notably, all outcome metrics will be collected at each time point after the consent appointment (baseline on, baseline off, 6 month and 12 month) with the exception of the quality of life metrics (Neuro-QoL and MDS-UPDRS I, II, IV) which will be collected at one of the two baseline assessments (instead of both baseline assessments), 6 month, and 12 month; the quality of life questionnaires ask questions about one's quality of life over the previous 7 days and are non-specific to medication state. Genetic data and demographics will be gathered at the first enrollment assessment visit. Following the two enrollment visits, the participant will begin attending PFP classes 3x/wk at the community center most convenient to them. Participants will be recruited and enrolled on a continuous basis.

Eligibility criteria: Inclusion Criteria:

1. Adult with a diagnosis of PD by a physician or physician extender
2. Hoehn and Yahr stage I-III
3. Demonstrate the ability to safely mount and dismount a stationary cycle
4. Reliable transportation to the community exercise facility
5. Smartphone device for activity data monitoring
6. On a stable dose of anti-parkinsonian medication

Exclusion Criteria:

1. Participation in disease modifying PD-related clinical trial or study
2. Diagnosis of dementia or any neurocognitive impairment that compromises one's ability to provide informed consent.
3. Implanted deep brain stimulation electrodes or focused ultrasound for PD management
4. Recommendation for medical clearance using the American College of Sports Medicine (ACSM) Preparticipation Health Screen a. If the ACSM screen recommends medical clearance, the participant must obtain medical clearance by their health care provider prior to participation.

b. Those who choose not to obtain physician clearance will not be eligible for participation.

e) A musculoskeletal issue (arthritis, osteoporosis, back problem) that would limit one's ability to engage in a cycling intervention f) Neurological disease other than Parkinson's disease (i.e. multiple sclerosis, stroke) g) Current cardiac arrhythmia

Primary outcomes:
measure: MDS-UPDRS III
timeFrame: Enrollment On and Off Medications, 6 months post-enrollment, and 12 months post-enrollment
Secondary outcomes:
measure: Nine Hole Peg Test
timeFrame: Enrollment On and Off Medications, 6 months post-enrollment, and 12 months post-enrollment
measure: Timed Up & Go
timeFrame: Enrollment On and Off Medications, 6 months post-enrollment, and 12 months post-enrollment
measure: Six Minute Walk Test
timeFrame: Enrollment On and Off Medications, 6 months post-enrollment, and 12 months post-enrollment
measure: Processing Speed
timeFrame: Enrollment On and Off Medications, 6 months post-enrollment, and 12 months post-enrollment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
Study officials:
References: