Clinical trial NCT06339398: To Evaluate the Dose-response Effects of a Defined Volume of Physical Exercise on the Change of Peripheral Biomarkers, Clinical Response and Brain Connectivity in Parkinson's Disease: a Prospective, Observational, Cohort Pilot Study
Official title: Dose-response Effects of Physical Exercise Standardized Volume on Peripheral Biomarkers, Clinical Response and Brain Connectivity in Parkinson's Disease: a Prospective, Observational, Cohort Pilot Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Physical exercise
Brain-derived neurotrophic factor (BDNF)
Lead sponsor: Casa di Cura San Raffaele Cassino
Sponsor class: NETWORK
Collaborators: name: IRCCS San Raffaele Roma
name: San Raffaele Telematic University
name: University of Rome Tor Vergata
name: University of Urbino "Carlo Bo"
First posted: 2024-04-01
Enrollment: 30
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Parkinson's Disease

Brief summary: This is a prospective, observational, cohort pilot study of standardize volume of aerobic exercise on changes in BDNF concentration at 4-weeks of exercise training among Parkinson disease patients.

Thirty (N=30) participants will be consecutively enrolled and assigned to 2 groups: 1) Extensive Rehabilitation Group (exercise volume: 180 METs-min/week) or 2) Intensive Rehabilitation Group (exercise volume: 1350 METs-min/week).

The primary objective is to evaluate the dose-response effects of two different rehabilitation settings, characterized by different workload (measured as energy expenditure), on blood BDNF levels.

Detailed description: This pilot observational study will evaluate the dose-response relationship between the volume of exercise, measured as METs-minutes/week, of two different rehabilitation settings to quantify the change in BDNF concentration in PD patients.

The study will also compare the changes induced by extensive and intensive rehabilitation settings in other neurotrophic factors and peripheral biomarkers, on motor and non-motor symptoms, kinematic parameters of gait, cognitive function, quality of life and the changes in cortical activity assessed with electroencephalogram (EEG) and in brain connectivity by functional magnetic resonance imaging (fMRI).

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Parkinson's Disease according to the United Kingdom (UK) Parkinson's Disease Society Brain Bank
* Aged between 30 and 80 years
* Disease stage II-III in "ON" phase according to modified Hoehn and Yahr (H\&Y)
* Having no severe cognitive impairment:

  * Mini-Mental State Examination-MMSE ≥24
  * Montreal Cognitive Assessment - MoCA ≥ 17/30
* Under stable dopaminergic pharmacological treatment
* Motor condition that permits to execute 6-Minutes Walking Test (6MWT)
* Willing to participate in the study, understand the procedures and sign the informed consent.

Exclusion Criteria:

* Diagnosis of neurological disorders not related to Parkinson's disease
* Musculoskeletal diseases that could impair gait and execution of exercise program
* Presence of known cardiovascular disease that can compromise the performance required by the protocol
* Presence of diabetes or other metabolic and endocrine disease
* Uncontrolled hypertension (resting blood pressure \>150/90 mmHg)
* Individuals with orthostatic hypotension and systolic pressure in feet below 100 will be excluded. Orthostatic hypotension (OH) is a reduction in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 minutes of standing.
* Hypo- or hyperthyroidism (TSH \<0.5 or \>5.0 mU/L), abnormal liver function (AST or ALT more than 2 times the upper limit of normal, ULN), alteration of kidney function.
* Values of complete blood test out of range and abnormal value clinically significant as per clinical judgment.
* Recent use of psychotropic drugs (e.g. anxiolytics, hypnotics, benzodiazepines, antidepressants) in which the dosage was not stable for 28 days before screening
* Severe disease (requiring systemic treatment and/or hospitalization) in the last 4 weeks.
* Any other clinically significant medical condition, psychiatric condition, drug or alcohol abuse, laboratory evaluation or abnormality that, in the opinion of the investigators, would interfere with the subject's ability to participate in the study.
* Beck Depression Inventory II (BDI) score \> 28, indicating a severe depression that precludes the ability to exercise.
* (Only for women) State of pregnancy.
* Other disorders, injuries, diseases or conditions that may interfere with the ability to perform exercises (e.g. history of stroke, breathing problems, traumatic brain injury, orthopaedic injury or neuromuscular disease).

Primary outcomes:
measure: Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)
timeFrame: 4 weeks
measure: Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)
timeFrame: 8 weeks
measure: Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)
timeFrame: 4 weeks
measure: Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)
timeFrame: 8 weeks
measure: Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)
timeFrame: 12 weeks
measure: Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin
timeFrame: 4 weeks
measure: Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin
timeFrame: 8 weeks
measure: Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin
timeFrame: 12 weeks
measure: Change in peripheral biomarker of inflammation
timeFrame: 4 weeks
measure: Change in peripheral biomarker of inflammation
timeFrame: 8 weeks
measure: Change in peripheral biomarker of inflammation
timeFrame: 12 weeks
measure: Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples
timeFrame: 4 weeks
measure: Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples
timeFrame: 8 weeks
measure: Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples
timeFrame: 12 weeks
measure: Change in blood lactate levels assessed using finger-stick capillary blood samples
timeFrame: 4 weeks
measure: Change in gut microbial diversity (species diversity %) assessed by next-generation sequencing (NGS) of the V3-V4 region of the 16S rDNA gene
timeFrame: 4 weeks
measure: Change in motor symptoms - MDS-UPDRS part II
timeFrame: 4 weeks
measure: Change in motor symptoms - MDS-UPDRS part II
timeFrame: 8 weeks
measure: Change in motor symptoms - MDS-UPDRS part II
timeFrame: 12 weeks
measure: Change in motor symptoms - MDS-UPDRS part III
timeFrame: 4 weeks
measure: Change in motor symptoms - MDS-UPDRS part III
timeFrame: 8 weeks
measure: Change in motor symptoms - MDS-UPDRS part III
timeFrame: 12 weeks
measure: Change in motor symptoms - MDS-UPDRS part IV
timeFrame: 4 weeks
measure: Change in motor symptoms - MDS-UPDRS part IV
timeFrame: 8 weeks
measure: Change in motor symptoms - MDS-UPDRS part IV
timeFrame: 12 weeks
measure: Change in movement analysis - stride length
timeFrame: 4 weeks
measure: Change in movement analysis - stride length
timeFrame: 8 weeks
measure: Change in movement analysis - stride length
timeFrame: 12 weeks
measure: Change in movement analysis - cadence
timeFrame: 4 weeks
measure: Change in movement analysis - cadence
timeFrame: 8 weeks
measure: Change in movement analysis - cadence
timeFrame: 12 weeks
measure: Change in movement analysis - propulsion
timeFrame: 4 weeks
measure: Change in movement analysis - propulsion
timeFrame: 8 weeks
measure: Change in movement analysis - propulsion
timeFrame: 12 weeks
measure: Change in movement analysis - Time Up and Go (TUG)
timeFrame: 4 weeks
measure: Change in movement analysis - Time Up and Go (TUG)
timeFrame: 8 weeks
measure: Change in movement analysis - Time Up and Go (TUG)
timeFrame: 12 weeks
measure: Change in walking capacity
timeFrame: 4 weeks
measure: Change in walking capacity
timeFrame: 8 weeks
measure: Change in walking capacity
timeFrame: 12 weeks
measure: Change in postural instability
timeFrame: 4 weeks
measure: Change in postural instability
timeFrame: 8 weeks
measure: Change in postural instability
timeFrame: 12 weeks
measure: Change in cognitive function - Montreal Cognitive Assessment (MoCA)
timeFrame: 4 weeks
measure: Change in cognitive function - Montreal Cognitive Assessment (MoCA)
timeFrame: 8 weeks
measure: Change in cognitive function - Montreal Cognitive Assessment (MoCA)
timeFrame: 12 weeks
measure: Change in cognitive function - Mini-Mental Examination (MMSE)
timeFrame: 4 weeks
measure: Change in cognitive function
timeFrame: 8 weeks
measure: Change in cognitive function
timeFrame: 12 weeks
measure: Change in cognitive function - Frontal Assessment Battery (FAB)
timeFrame: 4 weeks
measure: Change in cognitive function - Frontal Assessment Battery (FAB)
timeFrame: 8 weeks
measure: Change in cognitive function - Frontal Assessment Battery (FAB)
timeFrame: 12 weeks
measure: Change in severity of depressive symptomatology
timeFrame: 4 weeks
measure: Change in severity of depressive symptomatology
timeFrame: 8 weeks
measure: Change in severity of depressive symptomatology
timeFrame: 12 weeks
measure: Change in non-motor symptoms
timeFrame: 4 weeks
measure: Change in non-motor symptoms
timeFrame: 8 weeks
measure: Change in non-motor symptoms
timeFrame: 12 weeks
measure: Change in motor fluctuations
timeFrame: 4 weeks
measure: Change in motor fluctuations
timeFrame: 8 weeks
measure: Change in motor fluctuations
timeFrame: 12 weeks
measure: Change in quality of life
timeFrame: 4 weeks
measure: Change in quality of life
timeFrame: 8 weeks
measure: Change in quality of life
timeFrame: 12 weeks
measure: Change in cortical activity
timeFrame: 4 weeks
measure: Change in cortical activity
timeFrame: 12 weeks
measure: Change in Brain Connectivity
timeFrame: 4 weeks
measure: Change in Brain Connectivity
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cassino
country: Italy
facility: San Raffaele Cassino
state: Frosinone
Study officials:
affiliation: San Raffaele Cassino
name: Maria Francesca De Pandis, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: