Exercise for Cognitive Excellence in Parkinson's Disease

Parkinson Disease Clinical Trial

— EXCEL-PD  

Official title:

Exercise for Cognitive Excellence in Parkinson's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05720468
• Other study ID #: K23NS123506
• Secondary ID: K23NS123506
• Status: Recruiting
• Phase: N/A
• Start date: July 20, 2023
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: University of California, San Francisco
• Contact: Nijee Luthra, MD, PhD
• Phone: (415) 502-2960
• Email: nijee.luthra[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and feasibility of a home-based, virtually-supervised, combined high intensity endurance and resistance training program in people with Parkinson's disease. It will also evaluate the effects of exercise on cognition and underlying exercise-related biological markers (biomarkers).

Description:

Cognitive impairment begins early in Parkinson's disease (PD) and progresses to dementia in a majority of patients, impairing quality of life and contributing to growing health-related costs. Physical exercise has potent anti-aging effects and improves many outcomes in PD including cognition. Identifying biomarkers that respond to exercise, and how they associate with cognition and underlying disease pathology, may elucidate key mechanisms for countering cognitive decline. This is a randomized-controlled trial that evaluates safety and feasibility of a home-based exercise intervention in people with PD and measure its effects on cognition and circulating biomarkers of aging and stress. Thirty-six participants with PD will be randomized to receive a home-based, trainer-supervised endurance and resistance training program (exercise group) or no exercise (wait list control group) for 26 weeks. Cognitive assessments and patient reported outcomes will be obtained at baseline and at end of 26 weeks. Biomarkers in periphery (blood, saliva) and brain [cerebrospinal fluid (CSF)] will also be measured before and after the 26-week exercise intervention.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of idiopathic Parkinson's disease (PD) based on MDS criteria, with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity), without any other known or suspected cause of parkinsonism.

2. Modified Hoehn and Yahr stage less than 4

3. Age 40-80 years at time of screening

4. If being treated with PD symptomatic medications (i.e.g., rasagiline, carbidopa/levodopa, dopamine agonists, amantadine, anti-cholinergics), stable doses for greater than or equal to 2 months prior to baseline. If not being treated with PD symptomatic medication at time of screening, deemed unlikely to require symptomatic medication for next 6 months.

Exclusion Criteria:

1. A diagnosis of atypical parkinsonism, drug-induced parkinsonism, essential tremor, primary dystonia or other diagnoses that explain symptoms other than PD.

2. A diagnosis of a significant neurological disease other than PD that would interfere with ability to perform study procedures or assessments.

3. Significant cognitive impairment defined as Montreal Cognitive Assessment (MoCA)<23 or any impairment that would, in the opinion of the investigator, interfere with ability to follow exercise directions.

4. Beck Depression Inventory II (BDI) score > 16, indicating depression that precludes ability to exercise.

5. Use of neuroleptics/dopamine receptor blockers for more than 30 days in the year prior to baseline visit, or any use within 30 days of baseline visit.

6. Recent use of psychotropic medications (e.g., recent use of psychotropic medications (i.e., anxiolytics, hypnotics, benzodiazepines, antidepressants) where dosage has not been stable for more than 30 days prior to screening.

7. Presence of known cardiovascular, metabolic, or renal disease or individuals with major signs or symptoms suggestive of cardiovascular, metabolic, or renal disease without medical clearance to participate in the exercise program.

8. Presence of any of the following laboratory abnormalities on screening labs:

1. Abnormal liver function (AST or ALT more than 2 times the upper limit of normal)

2. Abnormal renal function (creatinine clearance calculated by the Cockcroft-Gault equation <50mL/min or estimated glomerular filtration rate using the MDRD4 equation or the CKD-EPI equation <45mL/min/1.73m2)

3. Complete Blood Count out of range on screening labs and physician's judgment that abnormal value is clinically significant.

9. Uncontrolled hypertension (resting blood pressure >150/90 mmHg).

10. Orthostatic hypotension and standing systolic BP below 100. Orthostatic hypotension is a reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 minutes of standing.

11. Already participating in 120 minutes or more of moderate intensity exercise per week.

12. Serious illness (requiring systemic treatment and/or hospitalization) within the last 4 weeks.

13. History of any other medical problem or injury that may interfere with ability to exercise.

14. Condition that precludes the safe performance of routine lumbar puncture, including:

1. INR > 1.4 or other coagulopathy

2. Platelet cell count of < 50,000/µL

3. Infection at the desired lumbar puncture site

4. Taking anti-coagulant medication within 90 days of baseline (Note: low dose aspirin is permitted)

5. Suspected non-communicating hydrocephalus or intracranial mass

6. Prohibitive lumbar spinal disease

15. Enrollment in another investigational study that includes an intervention; participation in non-interventional studies may be permitted

16. Receipt of any non-PD investigational product or device or participation in a non-PD drug research study within a period of 30 days (or 5 half-lives of the drug, whichever is longer) before baseline.

17. History of frequent falls (i.e. falling multiple times per week) or considered high fall risk based on investigator assessment

18. Lack of access to computer/tablet and WiFi or any other technical challenges that in the opinion of the investigator would prevent participation in the virtually supervised exercise training program.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Other:
• Exercise
Combined endurance and resistance exercise training
• No Exercise
Continue usual level of physical activity; option to participate in exercise training program after 26-week intervention period

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in motor symptoms of Parkinson's disease	Change from baseline in the Movement Disorders Society-Unified Parkinson Disease Rating Scale motor score (Part III). The minimum score on the MDS-UPDRS Part III is 0 and the maximum is 132 with higher scores representing worse motor symptoms.	26 weeks
Other	Change in isokinetic strength	Change from baseline in maximal knee extension measured in peak torque	Baseline and 26 weeks
Other	Change in isokinetic strength	Change from baseline in handgrip strength measured in kilograms using dynamometer	Baseline and 26 weeks
Other	Change in fitness	Change from baseline in maximal oxygen consumption measured with peak oxygen volume	Baseline and 26 weeks
Other	Change in walking capacity	Change from baseline in distance in 6-minute walk	Baseline and 26 weeks
Other	Change in quality of life	Change from baseline in quality of life measured with the Parkinson Disease Questionnaire-39 (PDQ-39). The PDQ-39 is a 39-item self-report questionnaire, which assesses Parkinson's disease-specific health related quality over the last month covering 8 dimensions scored on a 5 point ordinal system (0=never, 4=always). Dimension score = sum of scores of each item in the dimension divided by the maximum possible score of all the items in the dimension, multiplied by 100. Each dimension total score range from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better QoL. Overall score can be summarized in the Parkinson's Disease Summary Index (PDSI) or PDQ-39 Summary Index (PDQ-39 SI).PDSI or PDQ-39 SI = sum of dimension total scores divided by 8.	Baseline and 26 weeks
Other	Change in mood	Change from baseline in mood measuring using the Beck Depression Inventory (BDI-II). The BDI-II is a 21-item self-report inventory designed to measure the severity of depression symptomatology. Each item is evaluated on a severity scale ranging from 0-3, with a total score ranging from 0-63. A score of 0-13 is considered none or minimal range depression; 14-19 mild is considered mild depression; 20-28 is considered moderate depression and 29-63 is considered severe depression.	Baseline and 26 weeks
Other	Change in cognitive function	Change from baseline in the National Institute of Health Toolbox Cognitive Battery, a comprehensive, performance-based test comprised of motor, emotion, sensation, and cognition assessments. For the purpose of this study, the investigators will be using the cognitive battery to assess processes involved in learning and comprehension (i.e. thinking, remembering, problem-solving, judging). The battery consists of tasks involving the use of executive function, memory, attention, and language.	Baseline and 26 weeks
Other	Change in cognitive function	Change from baseline in alternate phonemic/semantic fluency test. This test measures executive cognitive function. Participants are required to alternate letter-cued words with category-cued words. Higher scores represent a better outcome.	Baseline and 26 weeks
Other	Change in cognitive function	Change from baseline in Trail Making Test. This test is commonly used for the evaluation of attentional processes and cognitive flexibility. The Trail Making Test contains two components. The first part only demands simpler attentional processes - seeking numbers spread throughout a page, while the second involves a flexibility component requiring the participant to switch between numbers and letters during the test run. Higher scores represent a worse outcome.	Baseline and 26 weeks
Primary	Average percent heart rate maximum (HR max)	The overall average percent HR max will be compared to the target percent HR max (80-85 percent).	From weeks 5-26, every exercise session
Primary	Average repetition maximum	The overall average repetition maximum for resistance exercise will be compared to the target repetition maximum (10-repetition maximum)	From weeks 5-26, every exercise session
Primary	Average number of days per week exercised	The average number of days per week exercised will be compared to target adherence (5 days/week of exercise)	From weeks 5-26, every week
Secondary	Change in cognitive function	Change from baseline in Montreal Cognitive Assessment (MoCA). MoCA scores range between 0 and 30, with higher scores representing a better outcome.	Baseline and 26 weeks
Secondary	Change in biomarker of aging	Change from baseline in blood levels of klotho	Baseline and 26 weeks
Secondary	Change in biomarker of aging	Change from baseline in CSF levels of klotho	Baseline and 26 weeks
Secondary	Change in biomarker of stress	Change from baseline in saliva levels of cortisol	Baseline and 26 weeks
Secondary	Change in biomarker of stress	Change from baseline in CSF levels of cortisol	Baseline and 26 weeks