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NCT Number: 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

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.

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Key information

Conditions

Parkinson Disease Basal Ganglia Diseases Behavior Brain Diseases Central Nervous System Diseases Motor Activity Movement Disorders Nervous System Diseases Neurodegenerative Diseases Parkinsonian Disorders Synucleinopathies

Age range

30 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Aerobic Exercise

Behavioral

Standardized volume of aerobic exercise, measured as METs-minutes/week

Primary outcomes

  1. Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)

    Time frame: 4 weeks

    Change from baseline (T0) in blood BDNF concentration

  2. Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)

    Time frame: 8 weeks

    Change from baseline (T0) in blood BDNF concentration

  3. Change in Brain-derived neurotrophic (BDNF) concentration assessed in peripheral blood samples (ng/mL)

    Time frame: 12 weeks

    Change from baseline (T0) in blood BDNF concentration

Secondary outcomes

  1. Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)

    Time frame: 4 weeks

    Change from baseline (T0) in peripheral blood IGF-1 concentration (μg/L)

  2. Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)

    Time frame: 8 weeks

    Change from baseline (T0) in peripheral blood IGF-1 concentration (μg/L)

  3. Change in peripheral biomarker Insulin-like Growth Factor-1 (IGF-1)

    Time frame: 12 weeks

    Change from baseline (T0) in peripheral blood IGF-1 concentration (μg/L)

  4. Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin

    Time frame: 4 weeks

    Change from baseline (T0) in FNDC5/Irisin by peripheral blood samples (ng/mL)

  5. Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin

    Time frame: 8 weeks

    Change from baseline (T0) in FNDC5/Irisin by peripheral blood samples (ng/mL)

  6. Change in peripheral biomarker Fibronectin type III domain-containing protein 5 (FNDC5)/Irisin

    Time frame: 12 weeks

    Change from baseline (T0) in FNDC5/Irisin by peripheral blood samples (ng/mL)

  7. Change in peripheral biomarker of inflammation

    Time frame: 4 weeks

    Change from baseline (T0) in high sensitivity C-reactive protein (CRP) assessed by peripheral blood samples (mg/L)

  8. Change in peripheral biomarker of inflammation

    Time frame: 8 weeks

    Change from baseline (T0) in high sensitivity C-reactive protein (CRP) assessed by peripheral blood samples (mg/L)

  9. Change in peripheral biomarker of inflammation

    Time frame: 12 weeks

    Change from baseline (T0) in high sensitivity C-reactive protein (CRP) assessed by peripheral blood samples (mg/L)

  10. Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples

    Time frame: 4 weeks

    Change from baseline (T0) in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples

  11. Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples

    Time frame: 8 weeks

    Change from baseline (T0) in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples

  12. Change in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples

    Time frame: 12 weeks

    Change from baseline (T0) in platelet distribution width (PDW) and number of platelets assessed by peripheral blood samples

  13. Change in blood lactate levels assessed using finger-stick capillary blood samples

    Time frame: 4 weeks

    Change from baseline (T0) in blood lactate levels (mM) assessed using finger-stick capillary blood samples

  14. Change in gut microbial diversity (species diversity %) assessed by next-generation sequencing (NGS) of the V3-V4 region of the 16S rDNA gene

    Time frame: 4 weeks

    Change from baseline (T0) in blood lactate levels (mM) assessed using finger-stick capillary blood samples

  15. Change in motor symptoms - MDS-UPDRS part II

    Time frame: 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

  16. Change in motor symptoms - MDS-UPDRS part II

    Time frame: 8 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

  17. Change in motor symptoms - MDS-UPDRS part II

    Time frame: 12 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

  18. Change in motor symptoms - MDS-UPDRS part III

    Time frame: 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

  19. Change in motor symptoms - MDS-UPDRS part III

    Time frame: 8 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

  20. Change in motor symptoms - MDS-UPDRS part III

    Time frame: 12 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

  21. Change in motor symptoms - MDS-UPDRS part IV

    Time frame: 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

  22. Change in motor symptoms - MDS-UPDRS part IV

    Time frame: 8 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

  23. Change in motor symptoms - MDS-UPDRS part IV

    Time frame: 12 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

  24. Change in movement analysis - stride length

    Time frame: 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)

  25. Change in movement analysis - stride length

    Time frame: 8 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)

  26. Change in movement analysis - stride length

    Time frame: 12 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)

  27. Change in movement analysis - cadence

    Time frame: 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)

  28. Change in movement analysis - cadence

    Time frame: 8 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)

  29. Change in movement analysis - cadence

    Time frame: 12 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)

  30. Change in movement analysis - propulsion

    Time frame: 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)

  31. Change in movement analysis - propulsion

    Time frame: 8 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)

  32. Change in movement analysis - propulsion

    Time frame: 12 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)

  33. Change in movement analysis - Time Up and Go (TUG)

    Time frame: 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)

  34. Change in movement analysis - Time Up and Go (TUG)

    Time frame: 8 weeks

    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)

  35. Change in movement analysis - Time Up and Go (TUG)

    Time frame: 12 weeks

    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)

  36. Change in walking capacity

    Time frame: 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)

  37. Change in walking capacity

    Time frame: 8 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)

  38. Change in walking capacity

    Time frame: 12 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)

  39. Change in postural instability

    Time frame: 4 weeks

    Change in Berg Balance Scale (BBS), which is a widely used clinical test to assess static and dynamic balance abilities

  40. Change in postural instability

    Time frame: 8 weeks

    Change in Berg Balance Scale (BBS), which is a widely used clinical test to assess static and dynamic balance abilities

  41. Change in postural instability

    Time frame: 12 weeks

    Change in Berg Balance Scale (BBS), which is a widely used clinical test to assess static and dynamic balance abilities

  42. Change in cognitive function - Montreal Cognitive Assessment (MoCA)

    Time frame: 4 weeks

    Change from baseline (T0) in the MoCA. MoCA scores range between 0 and 30, with higher scores representing a better outcome

  43. Change in cognitive function - Montreal Cognitive Assessment (MoCA)

    Time frame: 8 weeks

    Change from baseline (T0) in the MoCA. MoCA scores range between 0 and 30, with higher scores representing a better outcome

  44. Change in cognitive function - Montreal Cognitive Assessment (MoCA)

    Time frame: 12 weeks

    Change from baseline (T0) in the MoCA. MoCA scores range between 0 and 30, with higher scores representing a better outcome

  45. Change in cognitive function - Mini-Mental Examination (MMSE)

    Time frame: 4 weeks

    Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome

  46. Change in cognitive function

    Time frame: 8 weeks

    Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome

  47. Change in cognitive function

    Time frame: 12 weeks

    Change from baseline (T0) in the MMSE. MMSE scores range between 0 and 30, with higher scores representing a better outcome

  48. Change in cognitive function - Frontal Assessment Battery (FAB)

    Time frame: 4 weeks

    Change from baseline (T0) in the FAB. FAB scores range between 0 and 18, with higher scores representing a better outcome

  49. Change in cognitive function - Frontal Assessment Battery (FAB)

    Time frame: 8 weeks

    Change from baseline (T0) in the FAB. FAB scores range between 0 and 18, with higher scores representing a better outcome

  50. Change in cognitive function - Frontal Assessment Battery (FAB)

    Time frame: 12 weeks

    Change from baseline (T0) in the FAB. FAB scores range between 0 and 18, with higher scores representing a better outcome

  51. Change in severity of depressive symptomatology

    Time frame: 4 weeks

    Change from baseline (T0) in the Beck Depression Inventory-II (BDI-II).

  52. Change in severity of depressive symptomatology

    Time frame: 8 weeks

    Change from baseline (T0) in the Beck Depression Inventory-II (BDI-II).

  53. Change in severity of depressive symptomatology

    Time frame: 12 weeks

    Change from baseline (T0) in the Beck Depression Inventory-II (BDI-II).

  54. Change in non-motor symptoms

    Time frame: 4 weeks

    Change from baseline (T0) in Non-Motor Symptoms Scale (NMSS) in PD

  55. Change in non-motor symptoms

    Time frame: 8 weeks

    Change from baseline (T0) in Non-Motor Symptoms Scale (NMSS) in PD

  56. Change in non-motor symptoms

    Time frame: 12 weeks

    Change from baseline (T0) in Non-Motor Symptoms Scale (NMSS) in PD

  57. Change in motor fluctuations

    Time frame: 4 weeks

    Change from baseline (T0) in wearing OFF episodes will be assessed by Wearing OFF Questionnaire-19 (WOQ-19)

  58. Change in motor fluctuations

    Time frame: 8 weeks

    Change from baseline (T0) in wearing OFF episodes will be assessed by Wearing OFF Questionnaire-19 (WOQ-19)

  59. Change in motor fluctuations

    Time frame: 12 weeks

    Change from baseline (T0) in wearing OFF episodes will be assessed by Wearing OFF Questionnaire-19 (WOQ-19)

  60. Change in quality of life

    Time frame: 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).

  61. Change in quality of life

    Time frame: 8 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).

  62. Change in quality of life

    Time frame: 12 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).

  63. Change in cortical activity

    Time frame: 4 weeks

    Change from the baseline (T0) in the cortical activity will be measured with resting-state electroencephalography (rsEEG)

  64. Change in cortical activity

    Time frame: 12 weeks

    Change from the baseline (T0) in the cortical activity will be measured with resting-state electroencephalography (rsEEG)

  65. Change in Brain Connectivity

    Time frame: 4 weeks

    Change from the baseline (T0) in brain connectivity through functional magnetic resonance imaging (fMRI).

  66. Change in Brain Connectivity

    Time frame: 12 weeks

    Change from the baseline (T0) in brain connectivity through functional magnetic resonance imaging (fMRI).

Study contacts

Contact information is provided by the study sponsor or research team.

Maria Francesca De Pandis, MD, PhD

CONTACT

[email protected]

0039 0776394740

Maria Gaglione

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Casa di Cura San Raffaele Cassino

Network

Collaborators

  • IRCCS San Raffaele Roma
  • San Raffaele Telematic University
  • University of Rome Tor Vergata
  • University of Urbino "Carlo Bo"

Registry information

Official study 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

Acronym: METEX-PD

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Apr 1, 2024
Registry last updated
Feb 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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