Clinical trial NCT04379778: Aerobic Exercise and Brain Health in Parkinson's
Official title: Effects of Aerobic Exercise on Brain Health in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2020-05-07
Enrollment: 70
Sex: ALL
Minimum age (years): 40
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the project is to investigate how moderate to high intensity aerobic exercise affects brain health in patients with Parkinson's disease. Assessments include MRI, blood markers, cognition, functional tests, questionnaires, and cardiorespiratory fitness.

The study will be a single blinded randomized controlled trial with a 6-month long intervention.

Detailed description: Background: No approved medical treatments preventing, delaying or stopping Parkinson's disease (PD) exist, making identification of interventions having this potential a major priority. Exercise studies have demonstrated beneficial effects of aerobic exercise (AE) on aerobic capacity, cognition, depression and the Unified Parkinson's Disease Rating Scale (UPDRS). Animal studies show that AE can reduce α-synuclein aggregation and toxin-induced lesions in the nigrostriatal pathway while improving motor and cognitive function. Consequently, AE possesses neuroprotective potentials and thus represents a potentially inexpensive and easily accessible disease modifying therapy in PD. Evolving magnetic resonance imaging (MRI) techniques offer valid and reliable biomarkers to monitor disease progression, but no longitudinal MRI study has assessed the neuroprotective potentials of AE in PD.

Aim: To investigate whether 24 weeks of AE can delay PD progression markers and improve motor/non-motor symptoms in PD.

Methods: 70 PD patients will be randomized 1:1 to 24 weeks of supervised AE (60 sessions, moderate to high intensity) or standard care. Neuroprotective effects will be determined by MRI scans (R2\*, quantitative susceptibility mapping, diffusion kurtosis imaging, neuromelanin-weighted MRI, volumetry), blood markers and Levodopa equivalents. Clinical (MDS-UPDRS III) and subjective (MDS-UPDRS I) outcomes are also assessed.

Perspectives: By combining expertise from exercise physiology, radiology, endocrinology and neuropsychology a novel approach is taken aiming to understand the possible neuroprotective effects of AE in PD. This would be of high relevance to PD patients and their relatives. From a societal perspective it may lower disability-related costs by optimizing PD rehabilitation. In case of positive findings, this would provide the first convincing human evidence of a disease modifying effect of AE in PD potentially changing clinical practice.

Eligibility criteria: Inclusion Criteria:

* Informed consent
* Age ≥ 40 years
* Idiopathic PD diagnosis (within the previous five years)
* Patients in symptomatic therapy / not in therapy. Patients who are not already taking medication are not expected to need medication within 6 months of inclusion (in case of drug startup, this is noted)
* Hoehn \& Yahr ≤ 3
* Ability to transport oneself to and from exercise and testing

Exclusion Criteria:

* Alcohol abuse, depression, pacemaker
* Comorbidity/competing (neurological) disorder preventing participation in the intervention
* Pregnancy
* Metallic implants that prevent MRI.
* Expected exercise adherence below 85% of all planned sessions.
* Systematic moderate-high-level AE more than twice per week prior to start-up in the project

Primary outcomes:
measure: R2* MRI change
timeFrame: 0, 24 and 48 weeks
Secondary outcomes:
measure: QSM MRI change
timeFrame: 0, 24 and 48 weeks
measure: DKI MRI change
timeFrame: 0, 24 and 48 weeks
measure: Neuromelanin MRI change
timeFrame: 0, 24 and 48 weeks
measure: Volumetry MRI change
timeFrame: 0, 24 and 48 weeks
measure: Change in blood markers (e.g. α-synuclein)
timeFrame: 0, 24 and 48 weeks
measure: Change in Levodopa equivalents
timeFrame: 0, 24 and 48 weeks
measure: MDS-UPDRS change
timeFrame: 0, 24 and 48 weeks
measure: Aerobic capacity (VO2max test)
timeFrame: 0, 24 and 48 weeks
measure: Timed up and go (TUG) change
timeFrame: 0, 24 and 48 weeks
measure: 6 min walk test (6MWT) change
timeFrame: 0, 24 and 48 weeks
measure: Balance (Mini BESTest) change
timeFrame: 0, 24 and 48 weeks
measure: Cognition (The Montreal Cognitive Assessment (MoCA)) change
timeFrame: 0, 24 and 48 weeks
measure: Health-related quality of life (Parkinson's Disease Questionnaire (PDQ-39)) change
timeFrame: 0, 24 and 48 weeks
measure: Depression (Beck Depression Inventory-II (BDI-II)) change
timeFrame: 0, 24 and 48 weeks
measure: Non-motor symptoms (Non-Motor Symptoms Questionnaire (NMSQ)) change
timeFrame: 0, 24 and 48 weeks
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Sport Science, Department of Public Health, Aarhus University
state: Aarhus C
Study officials:
affiliation: University of Aarhus
name: Martin Langeskov-Christensen, Ph.d.
role: PRINCIPAL_INVESTIGATOR
References: