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RecruitingNCT06339398METEX-PDUpdated Sep 2, 2026

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

An observational study in Parkinson Disease, sponsored by Casa di Cura San Raffaele Cassino. Recruiting at 1 site in Italy. Open to participants aged 30 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-09-02.

Sponsored by Casa di Cura San Raffaele Cassino · Observational

From the registry’s dates

  • Started Feb 2025; still recruiting 1 year 7 months later.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
30
Ages
30 Years to 80 Years
Sex
All
01

Study 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.

Read the 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).

02

Conditions studied

  • Parkinson Disease

Keywords

  • Parkinson Disease
  • Physical exercise
  • Brain-derived neurotrophic factor (BDNF)
03

In context

Parkinson Disease

4,487 studies on the registry are indexed under Parkinson Disease; 1,082 are open to participants now.

This study's planned enrollment of 30 is below the median of 96 across 1,057 observational studies indexed under Parkinson Disease.

Browse Parkinson Disease studies →

Lead sponsor

Casa di Cura San Raffaele Cassino is the lead sponsor of 2 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Patients with Parkinson's Disease

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

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).
05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
30 participants (estimated)
Patient registry
No

Groups and cohorts

  • Extensive Rehabilitation Group

    PD patients of Extensive Group will perform a 45-minutes daily session of low-intensity aerobic exercise of 2-3 METs (37%-45% VO 2max ; 57-63% HR max) twice a week, for a 4-weeks period. Exercise volume: 180 METs-minutes/week

    Behavioral: Aerobic exercise

  • Intensive Rehabilitation Group

    PD patients of Intensive Rehabilitation Group will exercise for 45 minutes daily at high-intensity aerobic training of 6-8.8 METs (46-91% VO2max ; 76-95% HRmax), five days per week, for 4-weeks period. Exercise volume:1350 METs-minutes/week

    Behavioral: Aerobic exercise

Interventions

  • BehavioralAerobic exercise

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

06

What researchers measure

Primary outcomes

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

    Change from baseline (T0) in blood BDNF concentration

    Time frame: 4 weeks

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

    Change from baseline (T0) in blood BDNF concentration

    Time frame: 8 weeks

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

    Change from baseline (T0) in blood BDNF concentration

    Time frame: 12 weeks

Secondary outcomes

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

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

    Time frame: 4 weeks

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

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

    Time frame: 8 weeks

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

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

    Time frame: 12 weeks

  4. 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)

    Time frame: 4 weeks

  5. 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)

    Time frame: 8 weeks

  6. 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)

    Time frame: 12 weeks

  7. Change in peripheral biomarker of inflammation

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

    Time frame: 4 weeks

  8. Change in peripheral biomarker of inflammation

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

    Time frame: 8 weeks

  9. Change in peripheral biomarker of inflammation

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

    Time frame: 12 weeks

  10. 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

    Time frame: 4 weeks

  11. 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

    Time frame: 8 weeks

  12. 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

    Time frame: 12 weeks

  13. 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

    Time frame: 4 weeks

  14. 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

    Time frame: 4 weeks

  15. 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

    Time frame: 4 weeks

  16. 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

    Time frame: 8 weeks

  17. 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

    Time frame: 12 weeks

  18. 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

    Time frame: 4 weeks

  19. 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

    Time frame: 8 weeks

  20. 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

    Time frame: 12 weeks

  21. 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

    Time frame: 4 weeks

  22. 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

    Time frame: 8 weeks

  23. 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

    Time frame: 12 weeks

  24. 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)

    Time frame: 4 weeks

  25. 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)

    Time frame: 8 weeks

  26. 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)

    Time frame: 12 weeks

  27. 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)

    Time frame: 4 weeks

  28. 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)

    Time frame: 8 weeks

  29. 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)

    Time frame: 12 weeks

  30. 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)

    Time frame: 4 weeks

  31. 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)

    Time frame: 8 weeks

  32. 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)

    Time frame: 12 weeks

  33. 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)

    Time frame: 4 weeks

  34. 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)

    Time frame: 8 weeks

  35. 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)

    Time frame: 12 weeks

  36. 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)

    Time frame: 4 weeks

  37. 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)

    Time frame: 8 weeks

  38. 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)

    Time frame: 12 weeks

  39. Change in postural instability

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

    Time frame: 4 weeks

  40. Change in postural instability

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

    Time frame: 8 weeks

  41. Change in postural instability

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

    Time frame: 12 weeks

  42. 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

    Time frame: 4 weeks

  43. 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

    Time frame: 8 weeks

  44. 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

    Time frame: 12 weeks

  45. 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

    Time frame: 4 weeks

  46. 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

    Time frame: 8 weeks

  47. 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

    Time frame: 12 weeks

  48. 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

    Time frame: 4 weeks

  49. 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

    Time frame: 8 weeks

  50. 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

    Time frame: 12 weeks

  51. Change in severity of depressive symptomatology

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

    Time frame: 4 weeks

  52. Change in severity of depressive symptomatology

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

    Time frame: 8 weeks

  53. Change in severity of depressive symptomatology

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

    Time frame: 12 weeks

  54. Change in non-motor symptoms

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

    Time frame: 4 weeks

  55. Change in non-motor symptoms

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

    Time frame: 8 weeks

  56. Change in non-motor symptoms

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

    Time frame: 12 weeks

  57. Change in motor fluctuations

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

    Time frame: 4 weeks

  58. Change in motor fluctuations

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

    Time frame: 8 weeks

  59. Change in motor fluctuations

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

    Time frame: 12 weeks

  60. 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).

    Time frame: 4 weeks

  61. 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).

    Time frame: 8 weeks

  62. 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).

    Time frame: 12 weeks

  63. Change in cortical activity

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

    Time frame: 4 weeks

  64. Change in cortical activity

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

    Time frame: 12 weeks

  65. Change in Brain Connectivity

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

    Time frame: 4 weeks

  66. Change in Brain Connectivity

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

    Time frame: 12 weeks

07

Study locations

1 of 1 sites recruiting
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 2, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT06339398
Lead sponsor
Casa di Cura San Raffaele Cassino
Collaborators
IRCCS San Raffaele Roma, San Raffaele Telematic University, University of Rome Tor Vergata, University of Urbino "Carlo Bo"
Responsible party
Sponsor
First posted
Apr 1, 2024
Start date
Feb 11, 2025
Primary completion
Dec 31, 2027 (estimated)
Completion
May 31, 2028 (estimated)
Last update
Sep 2, 2026

Study contacts

Maria Francesca De Pandis, MD, PhD
Contact
maria.depandis@sanraffaele.it
0039 0776394740
Maria Gaglione
Contact
maria.gaglione@sanraffaele.it
Maria Francesca De Pandis, MD,PhD
principal investigator · San Raffaele Cassino

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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