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Exercise for Cognitive Excellence in Parkinson's Disease (EXCEL-PD)

Primary Purpose

Parkinson Disease

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise
No Exercise
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Modified Hoehn and Yahr stage less than 4 Age 40-80 years at time of screening 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: A diagnosis of atypical parkinsonism, drug-induced parkinsonism, essential tremor, primary dystonia or other diagnoses that explain symptoms other than PD. A diagnosis of a significant neurological disease other than PD that would interfere with ability to perform study procedures or assessments. 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. Beck Depression Inventory II (BDI) score > 16, indicating depression that precludes ability to exercise. 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. 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. 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. Presence of any of the following laboratory abnormalities on screening labs: Abnormal liver function (AST or ALT more than 2 times the upper limit of normal) 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) Complete Blood Count out of range on screening labs and physician's judgment that abnormal value is clinically significant. Uncontrolled hypertension (resting blood pressure >150/90 mmHg). 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. Already participating in 120 minutes or more of moderate intensity exercise per week. Serious illness (requiring systemic treatment and/or hospitalization) within the last 4 weeks. History of any other medical problem or injury that may interfere with ability to exercise. Condition that precludes the safe performance of routine lumbar puncture, including: INR > 1.4 or other coagulopathy Platelet cell count of < 50,000/μL Infection at the desired lumbar puncture site Taking anti-coagulant medication within 90 days of baseline (Note: low dose aspirin is permitted) Suspected non-communicating hydrocephalus or intracranial mass Prohibitive lumbar spinal disease Enrollment in another investigational study that includes an intervention; participation in non-interventional studies may be permitted 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. History of frequent falls (i.e. falling multiple times per week) or considered high fall risk based on investigator assessment 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.

Sites / Locations

  • University of California San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Exercise

Waitlist Control Group

Arm Description

Participants randomized to the exercise group will receive 26 weeks of home-based, combined endurance and resistance training program under guidance and virtual supervision from exercise trainers. Exercise will be performed 5 days per week, with 3 days of endurance training using treadmill and 2 days of resistance training.

The control group will continue usual level of physical activity the participants were doing prior to enrollment in the study. At the end of the 26 week study period, participants will be offered the chance to participate in the same home-based, combined endurance and resistance training program.

Outcomes

Primary Outcome Measures

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).
Average repetition maximum
The overall average repetition maximum for resistance exercise will be compared to the target repetition maximum (10-repetition maximum)
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)

Secondary Outcome Measures

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.
Change in biomarker of aging
Change from baseline in blood levels of klotho
Change in biomarker of aging
Change from baseline in CSF levels of klotho
Change in biomarker of stress
Change from baseline in saliva levels of cortisol
Change in biomarker of stress
Change from baseline in CSF levels of cortisol

Full Information

First Posted
January 31, 2023
Last Updated
September 13, 2023
Sponsor
University of California, San Francisco
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT05720468
Brief Title
Exercise for Cognitive Excellence in Parkinson's Disease
Acronym
EXCEL-PD
Official Title
Exercise for Cognitive Excellence in Parkinson's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 20, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Exercise
Arm Type
Experimental
Arm Description
Participants randomized to the exercise group will receive 26 weeks of home-based, combined endurance and resistance training program under guidance and virtual supervision from exercise trainers. Exercise will be performed 5 days per week, with 3 days of endurance training using treadmill and 2 days of resistance training.
Arm Title
Waitlist Control Group
Arm Type
Placebo Comparator
Arm Description
The control group will continue usual level of physical activity the participants were doing prior to enrollment in the study. At the end of the 26 week study period, participants will be offered the chance to participate in the same home-based, combined endurance and resistance training program.
Intervention Type
Other
Intervention Name(s)
Exercise
Intervention Description
Combined endurance and resistance exercise training
Intervention Type
Other
Intervention Name(s)
No Exercise
Intervention Description
Continue usual level of physical activity; option to participate in exercise training program after 26-week intervention period
Primary Outcome Measure Information:
Title
Average percent heart rate maximum (HR max)
Description
The overall average percent HR max will be compared to the target percent HR max (80-85 percent).
Time Frame
From weeks 5-26, every exercise session
Title
Average repetition maximum
Description
The overall average repetition maximum for resistance exercise will be compared to the target repetition maximum (10-repetition maximum)
Time Frame
From weeks 5-26, every exercise session
Title
Average number of days per week exercised
Description
The average number of days per week exercised will be compared to target adherence (5 days/week of exercise)
Time Frame
From weeks 5-26, every week
Secondary Outcome Measure Information:
Title
Change in cognitive function
Description
Change from baseline in Montreal Cognitive Assessment (MoCA). MoCA scores range between 0 and 30, with higher scores representing a better outcome.
Time Frame
Baseline and 26 weeks
Title
Change in biomarker of aging
Description
Change from baseline in blood levels of klotho
Time Frame
Baseline and 26 weeks
Title
Change in biomarker of aging
Description
Change from baseline in CSF levels of klotho
Time Frame
Baseline and 26 weeks
Title
Change in biomarker of stress
Description
Change from baseline in saliva levels of cortisol
Time Frame
Baseline and 26 weeks
Title
Change in biomarker of stress
Description
Change from baseline in CSF levels of cortisol
Time Frame
Baseline and 26 weeks
Other Pre-specified Outcome Measures:
Title
Change in motor symptoms of Parkinson's disease
Description
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.
Time Frame
26 weeks
Title
Change in isokinetic strength
Description
Change from baseline in maximal knee extension measured in peak torque
Time Frame
Baseline and 26 weeks
Title
Change in isokinetic strength
Description
Change from baseline in handgrip strength measured in kilograms using dynamometer
Time Frame
Baseline and 26 weeks
Title
Change in fitness
Description
Change from baseline in maximal oxygen consumption measured with peak oxygen volume
Time Frame
Baseline and 26 weeks
Title
Change in walking capacity
Description
Change from baseline in distance in 6-minute walk
Time Frame
Baseline and 26 weeks
Title
Change in quality of life
Description
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.
Time Frame
Baseline and 26 weeks
Title
Change in mood
Description
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.
Time Frame
Baseline and 26 weeks
Title
Change in cognitive function
Description
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.
Time Frame
Baseline and 26 weeks
Title
Change in cognitive function
Description
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.
Time Frame
Baseline and 26 weeks
Title
Change in cognitive function
Description
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.
Time Frame
Baseline and 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Modified Hoehn and Yahr stage less than 4 Age 40-80 years at time of screening 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: A diagnosis of atypical parkinsonism, drug-induced parkinsonism, essential tremor, primary dystonia or other diagnoses that explain symptoms other than PD. A diagnosis of a significant neurological disease other than PD that would interfere with ability to perform study procedures or assessments. 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. Beck Depression Inventory II (BDI) score > 16, indicating depression that precludes ability to exercise. 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. 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. 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. Presence of any of the following laboratory abnormalities on screening labs: Abnormal liver function (AST or ALT more than 2 times the upper limit of normal) 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) Complete Blood Count out of range on screening labs and physician's judgment that abnormal value is clinically significant. Uncontrolled hypertension (resting blood pressure >150/90 mmHg). 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. Already participating in 120 minutes or more of moderate intensity exercise per week. Serious illness (requiring systemic treatment and/or hospitalization) within the last 4 weeks. History of any other medical problem or injury that may interfere with ability to exercise. Condition that precludes the safe performance of routine lumbar puncture, including: INR > 1.4 or other coagulopathy Platelet cell count of < 50,000/μL Infection at the desired lumbar puncture site Taking anti-coagulant medication within 90 days of baseline (Note: low dose aspirin is permitted) Suspected non-communicating hydrocephalus or intracranial mass Prohibitive lumbar spinal disease Enrollment in another investigational study that includes an intervention; participation in non-interventional studies may be permitted 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. History of frequent falls (i.e. falling multiple times per week) or considered high fall risk based on investigator assessment 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nijee Luthra, MD, PhD
Phone
(415) 502-2960
Email
nijee.luthra@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nijee Luthra, MD, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94518
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nijee Luthra, MD, PhD
Phone
(415) 502-2960
Email
nijee.luthra@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Nijee Luthra, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Exercise for Cognitive Excellence in Parkinson's Disease

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