Effect of Exercise in Parkinsonism
Primary Purpose
Parkinson's Disease, Drug-induced Parkinsonism
Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Exercise
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson Disease, exercise
Eligibility Criteria
Inclusion Criteria:
- Veteran
Subjects with parkinsonian signs:
- rest tremor
- rigidity
- bradykinesia
Parkinsonian signs occurring after the institution of therapy with a medication having a known association with DIP, examples include:
- haloperidol
- chlorpromazine
- fluphenazine
- perphenazine
- risperidone
- thioridazine
- thiothixene
- lithium
- valproic acid
- ziprasidone
- olanzapine
- aripiprazole
- Potential subjects with DIP will be pre-screened using a brief (12 item) scratch and sniff smell test with hyposmic subjects invited to learn more about the study.
- clinical diagnosis of H/Y <=2 PD
Exclusion Criteria:
Subjects with a known diagnosis of atypical parkinsonian syndrome, i.e.:
- dementia with Lewy bodies
- progressive supranuclear palsy
- corticobasal degeneration
- multiple system atrophy)
- or other neurodegenerative condition
Subjects with a history of:
- sinus trauma or surgery
- encephalitis
- current nasal congestion or other known reason for olfactory impairment
- Subjects with a contraindication to DaTI (sensitivity or allergy to iodine, treatment with a drug with a significant effect on DaTscan that cannot be temporarily weaned)
- Subjects with known unstable cardiac, pulmonary, orthopedic or other conditions that would preclude safe participation in exercise training
- Subjects currently engaging in exercise more than 45 minutes per day, 3 days per week
Sites / Locations
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Exercise
No exercise
Arm Description
aerobic walking
normal activity
Outcomes
Primary Outcome Measures
change in dopamine transporter imaging
change in semi-quantitative Ioflupane-I123 uptake comparing exercise to no intervention
Secondary Outcome Measures
Full Information
NCT ID
NCT02598973
First Posted
November 4, 2015
Last Updated
April 8, 2021
Sponsor
VA Office of Research and Development
Collaborators
University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT02598973
Brief Title
Effect of Exercise in Parkinsonism
Official Title
Effect of Exercise on Recovery in Drug-Induced Parkinsonism and Parkinson Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2016 (Actual)
Primary Completion Date
January 31, 2021 (Actual)
Study Completion Date
January 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
Collaborators
University of Pennsylvania
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Parkinson's disease (PD) is a common neurodegenerative disorder affecting approximately 80,000 Veterans, representing a priority area for VA research. Current medicines for PD only improve symptoms, treatments that slow disease progression are needed, and earlier diagnosis of PD may be the key to their development. PD symptoms can be mimicked by medicines (most commonly antipsychotic drugs that block dopamine), and some of these patients actually have underlying "prodromal" PD that was "unmasked" years before it would have caused symptoms. This problem is increasing as these medicines are now used for common conditions including post-traumatic stress disorder and depression. The investigators will identify prodromal PD in patients with drug-induced symptoms using brain scans. These patients will be enrolled in a randomized clinical trial of aerobic exercise which slows progression in animal models of PD and has other health benefits. The investigators will measure the effect of exercise on symptoms, disease progression (using brain scans) and markers of PD risk (using blood tests). These studies will improve early PD diagnosis and potentially identify a way to slow progression of PD.
Detailed Description
Parkinson's disease (PD) is an incurable neurodegenerative disorder affecting approximately 1 million US adults and about 80,000 Veterans. PD causes significant morbidity due to motor and non-motor symptoms across its prolonged course with an annual economic burden of $14 billion in the US alone. Motor symptoms associated with loss of dopaminergic neurons in PD may be temporarily improved with dopamine replacing medicines, but disease-modifying therapies that delay or prevent neuronal loss are lacking and sorely needed. Exercise is promising as a disease-modifying therapy because it protects dopaminergic neurons in animal models of PD and has been associated with measures of neuroplasticity in PD patients. Unfortunately, more than half of dopaminergic neurons in the substantia nigra are lost before motor symptoms occur making it difficult to identify patients early enough to benefit from potentially disease-modifying therapies. Early "prodromal" PD can be identified using non-motor features including olfactory dysfunction and other biomarkers such as dopamine transporter (DaT) brain imaging abnormalities that are apparent years before motor symptoms. However, these strategies would be difficult and costly to implement on a population level without first identifying high-risk individuals for screening. Commonly prescribed dopamine blocking antipsychotic drugs cause debilitating PD-like motor dysfunction that is difficult to treat, and in some patients this finding may serve as a "stress test" for failing dopaminergic networks unmasking symptoms long before they would normally appear. Identifying prodromal PD among drug-induced parkinsonism patients offers a unique and unexplored opportunity for early intervention.
In the proposed studies, the investigators will employ a tiered screening strategy with inexpensive and non-invasive olfactory testing in drug-induced parkinsonism patients followed by DaT imaging in individuals with olfactory impairment to identify a cohort of patients with presumed prodromal PD. Subjects with presumed prodromal PD will then be randomized to a home-based exercise intervention ({5} times weekly aerobic walking confirmed by remote activity monitors) or no intervention. In this cohort, the investigators will assess: 1) Short-term symptomatic effects of exercise on motor function in drug-induced parkinsonism using standard clinical measures (Unified Parkinson's Disease Rating Scale) and quantitative gait assessments after 8 weeks of intervention; 2) a potential disease-modifying effect after 52 weeks of exercise by comparing the rate of change in quantitative DaT imaging; and 3) the mechanisms and biochemical correlates of exercise-induced changes using a panel of serum biomarkers implicated in exercise and/or PD risk including brain-derived neurotrophic factor, uric acid, and apolipoproteinA1. Differences in the rate of change between groups will be assessed using independent samples t-tests and linear mixed-effects models adjusting for age and gender. The investigators' preliminary data demonstrates a strong association between olfactory impairment and abnormal DaT imaging in drug-induced parkinsonism. Based on power calculations allowing for 20% dropout, the investigators will screen approximately 250 drug-induced parkinsonism subjects using olfactory testing, with the expectation that approximately 88 will have abnormal DaT imaging and agree to participate in the intervention trial.
Antipsychotic drugs are widely prescribed for a growing list of approved indications and off-label uses including bipolar disorder, depression and post-traumatic stress disorder. Studying drug-induced parkinsonism patients with prodromal PD will allow us to identify which individuals are at risk, characterize the natural history of progression and evaluate appropriate management strategies at the earliest stages of PD. Exercise as a putative disease-modifying therapy offers significant advantages including cost, ease of access and lack of toxicity compared with unproven pharmacologic interventions especially if offered early enough to have meaningful clinical impact.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease, Drug-induced Parkinsonism
Keywords
Parkinson Disease, exercise
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Exercise
Arm Type
Active Comparator
Arm Description
aerobic walking
Arm Title
No exercise
Arm Type
No Intervention
Arm Description
normal activity
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Intervention Description
Aerobic walking
Primary Outcome Measure Information:
Title
change in dopamine transporter imaging
Description
change in semi-quantitative Ioflupane-I123 uptake comparing exercise to no intervention
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Veteran
Subjects with parkinsonian signs:
rest tremor
rigidity
bradykinesia
Parkinsonian signs occurring after the institution of therapy with a medication having a known association with DIP, examples include:
haloperidol
chlorpromazine
fluphenazine
perphenazine
risperidone
thioridazine
thiothixene
lithium
valproic acid
ziprasidone
olanzapine
aripiprazole
Potential subjects with DIP will be pre-screened using a brief (12 item) scratch and sniff smell test with hyposmic subjects invited to learn more about the study.
clinical diagnosis of H/Y <=2 PD
Exclusion Criteria:
Subjects with a known diagnosis of atypical parkinsonian syndrome, i.e.:
dementia with Lewy bodies
progressive supranuclear palsy
corticobasal degeneration
multiple system atrophy)
or other neurodegenerative condition
Subjects with a history of:
sinus trauma or surgery
encephalitis
current nasal congestion or other known reason for olfactory impairment
Subjects with a contraindication to DaTI (sensitivity or allergy to iodine, treatment with a drug with a significant effect on DaTscan that cannot be temporarily weaned)
Subjects with known unstable cardiac, pulmonary, orthopedic or other conditions that would preclude safe participation in exercise training
Subjects currently engaging in exercise more than 45 minutes per day, 3 days per week
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James F Morley, MD
Organizational Affiliation
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Official's Role
Principal Investigator
Facility Information:
Facility Name
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Effect of Exercise in Parkinsonism
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