Parkinson Disease
Conditions
Keywords
Parkinson Disease, Physical exercise, Brain-derived neurotrophic factor (BDNF)
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).
Interventions
BEHAVIORALAerobic exercise
Standardized volume of aerobic exercise, measured as METs-minutes/week
Sponsors
University of Rome Tor Vergata
University of Urbino "Carlo Bo"
Casa di Cura San Raffaele Cassino
IRCCS San Raffaele Roma
San Raffaele Telematic University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL) | 4 weeks | Change from baseline (T0) in blood BDNF concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1) | 4 weeks | Change from baseline (T0) in peripheral blood IGF-1 concentration (μg/L) |
| Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin | 4 weeks | Change from baseline (T0) in FNDC5/Irisin by peripheral blood samples (ng/mL) |
| Change in peripheral biomarker of inflammation | 4 weeks | Change from baseline (T0) in high sensitivity C-reactive protein (CRP) assessed by peripheral blood samples (mg/L) |
| Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples | 4 weeks | Change from baseline (T0) in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples |
| Change in blood lactate levels assessed using finger-stick capillary blood samples | 4 weeks | Change from baseline (T0) in blood lactate levels (mM) assessed using finger-stick capillary blood samples |
| Change in gut microbial diversity (species diversity %) assessed by next-generation sequencing (NGS) of the V3-V4 region of the 16S rDNA gene | 4 weeks | Change from baseline (T0) in blood lactate levels (mM) assessed using finger-stick capillary blood samples |
| Change in motor symptoms - MDS-UPDRS part II | 4 weeks | Change from baseline (T0) in Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II (motor symptoms of daily living). The minimum score on the MDS-UPDRS Part II is 0 and the maximum is 52 with higher scores representing worse motor symptoms of daily living |
| Change in motor symptoms - MDS-UPDRS part III | 4 weeks | Change from baseline (T0) in Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor examination). The minimum score on the MDS-UPDRS Part III is 0 and the maximum is 132 with higher scores representing worse motor symptoms |
| Change in motor symptoms - MDS-UPDRS part IV | 4 weeks | Change from baseline (T0) in Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV (motor complication). The minimum score on the MDS-UPDRS Part IV is 0 and the maximum is 24 with higher scores representing worse motor complication |
| Change in movement analysis - stride length | 4 weeks | Change from baseline (T0) in stride length \[m\], the distance between two consecutive hell strikes of the same foot evaluated by using a wearable device (G-sensor, BTS Bioengineering, Milan) |
| Change in movement analysis - cadence | 4 weeks | Change from baseline (T0) in cadence \[steps/min\], the number of steps in a minute evaluated by using a wearable device (G-sensor, BTS Bioengineering, Milan) |
| Change in movement analysis - propulsion | 4 weeks | Change from baseline (T0) in propulsion \[m/ss\], the anterior-posterior acceleration peak during the lower limb swing phase evaluated by using a wearable device (G-sensor, BTS Bioengineering, Milan) |
| Change in movement analysis - Time Up and Go (TUG) | 4 weeks | Change from baseline (T0) in execution timing of TUG, a reliable and valid test for assessing mobility, balance, walking ability and fall risk, by using a wearable device (G-sensor, BTS Bioengineering, Milan) |
| Change in walking capacity | 4 weeks | Change from baseline (T0) in functional capacity evaluated by 6-minute Walking Test (6MWT), a standardized method to assess the maximal patient's capacity to walk as far as possible (measured in meters) |
| Change in postural instability | 4 weeks | Change in Berg Balance Scale (BBS), which is a widely used clinical test to assess static and dynamic balance abilities |
| Change in cognitive function - Montreal Cognitive Assessment (MoCA) | 4 weeks | Change from baseline (T0) in the MoCA. MoCA scores range between 0 and 30, with higher scores representing a better outcome |
| Change in cognitive function - Mini-Mental Examination (MMSE) | 4 weeks | Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome |
| Change in cognitive function | 8 weeks | Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome |
| Change in cognitive function - Frontal Assessment Battery (FAB) | 4 weeks | Change from baseline (T0) in the FAB. FAB scores range between 0 and 18, with higher scores representing a better outcome |
| Change in severity of depressive symptomatology | 4 weeks | Change from baseline (T0) in the Beck Depression Inventory-II (BDI-II). |
| Change in non-motor symptoms | 4 weeks | Change from baseline (T0) in Non-Motor Symptoms Scale (NMSS) in PD |
| Change in motor fluctuations | 4 weeks | Change from baseline (T0) in wearing OFF episodes will be assessed by Wearing OFF Questionnaire-19 (WOQ-19) |
| Change in quality of life | 4 weeks | Change from baseline (T0) in will be measured with PDQ-39 questionnaire, which assesses how often PD patients experience difficulties across eight dimensions of daily living (0=never, 4=always). |
| Change in cortical activity | 4 weeks | Change from the baseline (T0) in the cortical activity will be measured with resting-state electroencephalography (rsEEG) |
| Change in Brain Connectivity | 4 weeks | Change from the baseline (T0) in brain connectivity through functional magnetic resonance imaging (fMRI). |
Countries
Italy
Contacts
CONTACTMaria Francesca De Pandis, MD, PhD
CONTACTMaria Gaglione
PRINCIPAL_INVESTIGATORMaria Francesca De Pandis, MD,PhD
San Raffaele Cassino
Outcome results
None listed