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

Parkinson Disease Clinical Trial

— METEX-PD  

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06339398
• Other study ID #: 002-2023
• Status: Enrolling by invitation
• Start date: May 2024
• Est. completion date: May 31, 2028

Study information

• Verified date: March 2024
• Source: Casa di Cura San Raffaele Cassino
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 30
• Est. completion date: May 31, 2028
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Behavioral:
• Aerobic exercise
Standardized volume of aerobic exercise, measured as METs-minutes/week

Locations

Country	Name	City	State
Italy	San Raffaele Cassino	Cassino	Frosinone

Sponsors (5)

Lead Sponsor	Collaborator
Casa di Cura San Raffaele Cassino	IRCCS San Raffaele Roma, San Raffaele Telematic University, University of Rome Tor Vergata, University of Urbino "Carlo Bo"

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)	Change from baseline (T0) in blood BDNF concentration	4 weeks
Primary	Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)	Change from baseline (T0) in blood BDNF concentration	8 weeks
Primary	Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)	Change from baseline (T0) in blood BDNF concentration	12 weeks
Secondary	Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)	Change from baseline (T0) in peripheral blood IGF-1 concentration (µg/L)	4 weeks
Secondary	Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)	Change from baseline (T0) in peripheral blood IGF-1 concentration (µg/L)	8 weeks
Secondary	Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)	Change from baseline (T0) in peripheral blood IGF-1 concentration (µg/L)	12 weeks
Secondary	Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin	Change from baseline (T0) in FNDC5/Irisin by peripheral blood samples (ng/mL)	4 weeks
Secondary	Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin	Change from baseline (T0) in FNDC5/Irisin by peripheral blood samples (ng/mL)	8 weeks
Secondary	Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin	Change from baseline (T0) in FNDC5/Irisin by peripheral blood samples (ng/mL)	12 weeks
Secondary	Change in peripheral biomarker of inflammation	Change from baseline (T0) in high sensitivity C-reactive protein (CRP) assessed by peripheral blood samples (mg/L)	4 weeks
Secondary	Change in peripheral biomarker of inflammation	Change from baseline (T0) in high sensitivity C-reactive protein (CRP) assessed by peripheral blood samples (mg/L)	8 weeks
Secondary	Change in peripheral biomarker of inflammation	Change from baseline (T0) in high sensitivity C-reactive protein (CRP) assessed by peripheral blood samples (mg/L)	12 weeks
Secondary	Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples	Change from baseline (T0) in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples	4 weeks
Secondary	Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples	Change from baseline (T0) in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples	8 weeks
Secondary	Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples	Change from baseline (T0) in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples	12 weeks
Secondary	Change in blood lactate levels assessed using finger-stick capillary blood samples	Change from baseline (T0) in blood lactate levels (mM) assessed using finger-stick capillary blood samples	4 weeks
Secondary	Change in gut microbial diversity (species diversity %) assessed by next-generation sequencing (NGS) of the V3-V4 region of the 16S rDNA gene	Change from baseline (T0) in blood lactate levels (mM) assessed using finger-stick capillary blood samples	4 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part II	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	4 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part II	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	8 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part II	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	12 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part III	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	4 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part III	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	8 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part III	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	12 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part IV	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	4 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part IV	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	8 weeks
Secondary	Change in motor symptoms - MDS-UPDRS part IV	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	12 weeks
Secondary	Change in movement analysis - stride length	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)	4 weeks
Secondary	Change in movement analysis - stride length	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)	8 weeks
Secondary	Change in movement analysis - stride length	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)	12 weeks
Secondary	Change in movement analysis - cadence	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)	4 weeks
Secondary	Change in movement analysis - cadence	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)	8 weeks
Secondary	Change in movement analysis - cadence	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)	12 weeks
Secondary	Change in movement analysis - propulsion	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)	4 weeks
Secondary	Change in movement analysis - propulsion	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)	8 weeks
Secondary	Change in movement analysis - propulsion	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)	12 weeks
Secondary	Change in movement analysis - Time Up and Go (TUG)	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)	4 weeks
Secondary	Change in movement analysis - Time Up and Go (TUG)	Change from baseline (T0) in execution timing of Time Up and Go (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)	8 weeks
Secondary	Change in movement analysis - Time Up and Go (TUG)	Change from baseline (T0) in execution timing of Time Up and Go (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)	12 weeks
Secondary	Change in walking capacity	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)	4 weeks
Secondary	Change in walking capacity	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)	8 weeks
Secondary	Change in walking capacity	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)	12 weeks
Secondary	Change in postural instability	Change in Berg Balance Scale (BBS), which is a widely used clinical test to assess static and dynamic balance abilities	4 weeks
Secondary	Change in postural instability	Change in Berg Balance Scale (BBS), which is a widely used clinical test to assess static and dynamic balance abilities	8 weeks
Secondary	Change in postural instability	Change in Berg Balance Scale (BBS), which is a widely used clinical test to assess static and dynamic balance abilities	12 weeks
Secondary	Change in cognitive function - Montreal Cognitive Assessment (MoCA)	Change from baseline (T0) in the MoCA. MoCA scores range between 0 and 30, with higher scores representing a better outcome	4 weeks
Secondary	Change in cognitive function - Montreal Cognitive Assessment (MoCA)	Change from baseline (T0) in the MoCA. MoCA scores range between 0 and 30, with higher scores representing a better outcome	8 weeks
Secondary	Change in cognitive function - Montreal Cognitive Assessment (MoCA)	Change from baseline (T0) in the MoCA. MoCA scores range between 0 and 30, with higher scores representing a better outcome	12 weeks
Secondary	Change in cognitive function - Mini-Mental Examination (MMSE)	Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome	4 weeks
Secondary	Change in cognitive function	Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome	8 weeks
Secondary	Change in cognitive function	Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome	12 weeks
Secondary	Change in cognitive function - Frontal Assessment Battery (FAB)	Change from baseline (T0) in the FAB. FAB scores range between 0 and 18, with higher scores representing a better outcome	4 weeks
Secondary	Change in cognitive function - Frontal Assessment Battery (FAB)	Change from baseline (T0) in the FAB. FAB scores range between 0 and 18, with higher scores representing a better outcome	8 weeks
Secondary	Change in cognitive function - Frontal Assessment Battery (FAB)	Change from baseline (T0) in the FAB. FAB scores range between 0 and 18, with higher scores representing a better outcome	12 weeks
Secondary	Change in severity of depressive symptomatology	Change from baseline (T0) in the Beck Depression Inventory-II (BDI-II).	4 weeks
Secondary	Change in severity of depressive symptomatology	Change from baseline (T0) in the Beck Depression Inventory-II (BDI-II).	8 weeks
Secondary	Change in severity of depressive symptomatology	Change from baseline (T0) in the Beck Depression Inventory-II (BDI-II).	12 weeks
Secondary	Change in non-motor symptoms	Change from baseline (T0) in Non-Motor Symptoms Scale (NMSS) in PD	4 weeks
Secondary	Change in non-motor symptoms	Change from baseline (T0) in Non-Motor Symptoms Scale (NMSS) in PD	8 weeks
Secondary	Change in non-motor symptoms	Change from baseline (T0) in Non-Motor Symptoms Scale (NMSS) in PD	12 weeks
Secondary	Change in motor fluctuations	Change from baseline (T0) in wearing OFF episodes will be assessed by Wearing OFF Questionnaire-19 (WOQ-19)	4 weeks
Secondary	Change in motor fluctuations	Change from baseline (T0) in wearing OFF episodes will be assessed by Wearing OFF Questionnaire-19 (WOQ-19)	8 weeks
Secondary	Change in motor fluctuations	Change from baseline (T0) in wearing OFF episodes will be assessed by Wearing OFF Questionnaire-19 (WOQ-19)	12 weeks
Secondary	Change in quality of life	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).	4 weeks
Secondary	Change in quality of life	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).	8 weeks
Secondary	Change in quality of life	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).	12 weeks
Secondary	Change in cortical activity	Change from the baseline (T0) in the cortical activity will be measured with resting-state electroencephalography (rsEEG)	4 weeks
Secondary	Change in cortical activity	Change from the baseline (T0) in the cortical activity will be measured with resting-state electroencephalography (rsEEG)	12 weeks
Secondary	Change in Brain Connectivity	Change from the baseline (T0) in brain connectivity through functional magnetic resonance imaging (fMRI).	4 weeks
Secondary	Change in Brain Connectivity	Change from the baseline (T0) in brain connectivity through functional magnetic resonance imaging (fMRI).	12 weeks