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Trial record 1 of 265 for:    Exercise and Parkinsonism
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Effect of Exercise in Parkinsonism

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ClinicalTrials.gov Identifier: NCT02598973
Recruitment Status : Recruiting
First Posted : November 6, 2015
Last Update Posted : September 6, 2019
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
VA Office of Research and Development

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug-induced Parkinsonism Behavioral: Exercise Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Exercise on Recovery in Drug-Induced Parkinsonism and Parkinson Disease
Actual Study Start Date : February 1, 2016
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Exercise
aerobic walking
Behavioral: Exercise
Aerobic walking

No Intervention: No exercise
normal activity



Primary Outcome Measures :
  1. change in dopamine transporter imaging [ Time Frame: 1 year ]
    change in semi-quantitative Ioflupane-I123 uptake comparing exercise to no intervention



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02598973


Contacts
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Contact: James F Morley, MD (215) 823-5800 James.Morley@va.gov

Locations
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United States, Pennsylvania
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: James F Morley, MD    215-823-5800    James.Morley@va.gov   
Principal Investigator: James F Morley, MD         
Sponsors and Collaborators
VA Office of Research and Development
University of Pennsylvania
Investigators
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Principal Investigator: James F Morley, MD Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02598973    
Other Study ID Numbers: N2012-W
First Posted: November 6, 2015    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by VA Office of Research and Development:
Parkinson Disease
exercise
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Parkinson Disease, Secondary
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases