An observational study in Parkinson Disease, Physical Inactivity and Physical Disability, sponsored by IRCCS National Neurological Institute "C. Mondino" Foundation. Recruiting at 1 site in Italy. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-05-18.
Sponsored by IRCCS National Neurological Institute "C. Mondino" Foundation · Observational
Parkinson's Disease (PD) is a chronic progressive neurodegenerative disorder clinically defined by the association of resting tremor, rigidity, bradykinesia, and postural instability. The histopathology of PD is characterized by the loss of neurons in the substantia nigra pars compacta (SNPc) and the accumulation of α-synuclein aggregates within Lewy bodies. The pathogenic mechanisms underlying the development of the disease, however, are not yet fully understood: genetics, cellular oxidative stress, mitochondrial dysfunction, environmental factors, and neuroinflammation are all potential mechanisms involved in the pathogenesis of PD.
Several studies have now established the involvement of neuroinflammation in the pathogenesis of PD. It is known that α-synuclein aggregates stimulate microglia and astroglia to secrete pro-inflammatory mediators such as IL 1β, IL6, and TNFα. These molecules activate an inflammatory response characterized by altered blood-brain barrier permeability, leukocyte recruitment, and the expression of other pro-inflammatory cytokines. These events contribute to exposing neurons to oxidative stress and cellular damage. Additionally, cellular damage induces neurons to stimulate the release of DAMPs (Damage Associated Molecular Patterns), which in turn activate glial cells. This creates a state of chronic inflammation that could play a role in the progression of the disease. Supporting this hypothesis, elevated levels of IL1β, IL6, and TNFα have been found in the striatum and SNPc of post-mortem PD samples.
The transcription factor Nrf2 is one of the main regulators of cellular protection in response to stress (inflammation, redox, xenobiotics). Nrf2 promotes the expression of several genes that cooperate in a cytoprotective response, which includes antioxidant defense, resolution of inflammation, increased mitochondrial activity, and protein turnover. Recent clinical studies seem to confirm the hypothesis that Nrf2 plays a role in the pathogenesis of PD, as already suggested by preclinical models. Specifically, altered plasma levels of the Nrf2-activated pathway have been observed in preclinical models.
Studies conducted on animal models of PD have hypothesized how exercise might correlate with protective mechanisms and might promote neuroplasticity and neuro-regeneration, especially when practiced at high intensity. Physical exercise can indeed modulate various systems (including inflammatory pathways and oxidative stress) that regulate neuroinflammation and glial activation. However, the available results are not definitive and often focus on single and separate aspects of the disease.
The aim of the study is to investigate the beneficial effect of physical exercise in patients with Parkinson's Disease (PD). Literature already suggests an improvement in various domains of motor and non-motor aspects, as well as in the overall quality of life, of PD patients even after a period of aerobic activity. Generally, training periods included 3-4 sessions per week of 40-60 minutes each for 4-16 weeks. In general, the literature describes the effects of moderate physical training, while little or nothing is known about how PD is affected by high-intensity sports training.
The primary objective of our study is to compare a group of PD patients undergoing regular and constant intense exercise (PD-sport) with a control group consisting of PD patients leading a sedentary life (PD-sedentary). The primary outcome will be the difference in systemic inflammatory status between the PD-sport group and the PD-sedentary group.
Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder clinically defined by the presence of resting tremor, rigidity, bradykinesia, and postural instability. Pathologically, PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of α-synuclein aggregates within Lewy bodies. While the precise pathogenic mechanisms underlying PD remain incompletely understood, evidence suggests a multifactorial etiology involving genetic predisposition, oxidative stress, mitochondrial dysfunction, environmental factors, and neuroinflammation.
Emerging research highlights the pivotal role of neuroinflammation in PD pathogenesis. α-Synuclein aggregates are known to activate microglia and astroglia, triggering the release of pro-inflammatory mediators such as IL-1β, IL-6, and TNF-α. This inflammatory response disrupts blood-brain barrier integrity, recruits leukocytes, and amplifies the production of other pro-inflammatory cytokines, exposing neurons to oxidative stress and cellular damage. In turn, neuronal damage promotes the release of damage-associated molecular patterns (DAMPs), perpetuating chronic inflammation. Elevated levels of IL-1β, IL-6, and TNF-α have been detected in the striatum and SNpc of post-mortem PD samples, underscoring the role of inflammation in disease progression.
The transcription factor Nrf2 is a master regulator of cellular defense mechanisms against oxidative and inflammatory stress. Nrf2 orchestrates the expression of genes involved in antioxidant defense, inflammation resolution, mitochondrial activity, and protein turnover. Clinical and preclinical studies suggest that dysregulation of the Nrf2 pathway may contribute to PD pathogenesis, as evidenced by altered plasma levels of Nrf2-regulated pathways in preclinical PD models.
Animal studies have proposed that physical exercise may confer neuroprotective effects by promoting neuroplasticity and neuro-regeneration, particularly through high-intensity training. Exercise has been shown to modulate inflammatory pathways, reduce oxidative stress, and influence glial activation. Despite promising results, most studies have focused on isolated aspects, leaving gaps in our understanding of the comprehensive effects of exercise on PD.
This study aims to investigate the beneficial effects of adapted physical exercise in patients with PD, focusing on its impact on systemic inflammation and secondary outcomes such as gait parameters, functional markers of exercise tolerance, and quality of life.
Study Design
Primary objective: Evaluate differences in systemic inflammatory status between PD-sport and PD-sedentary groups.
Secondary and Exploratory objective
Recruitment
Participants will be recruited at the IRCCS Mondino Foundation of Pavia, and patient associations. The study will enroll two groups:
Evaluation
Assessments will include:
Comprehensive clinical evaluation by a movement disorder specialist. Biochemical analysis of inflammatory markers from fasting blood samples (35 mL).
Gait analysis using the G-Walk system. Cognitive and psychological evaluations. Exercise tolerance indices measured via cardiopulmonary exercise testing.
4,573 studies on the registry are indexed under Parkinson Disease; 1,086 are open to participants now.
This study's planned enrollment of 40 is below the median of 96 across 1,085 observational studies indexed under Parkinson Disease.
Browse Parkinson Disease studies →IRCCS National Neurological Institute "C. Mondino" Foundation is the lead sponsor of 57 studies on the registry; 20 are open to participants now.
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The study population consists of individuals diagnosed with Parkinson's disease, but without other clinically relevant medical conditions.
PD-sport group: this population will include a group of PD subjects who regularly performed a high-intensity and regular physical activity (based on IPAQ questionnaire).
PD-sedentary group: this population will include a group of PD subjects who did not regularly performed regular physical activity (based on IPAQ questionnaire).
The absence of other pathological and voluptuary condition is intended to reduce to possible biases of confounders on the inflammatory status.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In PD-SPORT group the investigators aim to enroll subjects affected by Parkinson's Disease who regularly performed intensive physical activity. For the purpose of this study, the intensive physical activity is defined by the International Physical Activity questionnaire (IPAQ).
In PD-SEDENTARY group the investigators aim to enroll subjects affected by Parkinson's Disease who did not regularly performed intensive physical activity. For the purpose of this study, the intensive of physical activity is defined by the International Physical Activity questionnaire (IPAQ).
Set of serum pro-inflammatory and anti-inflammatory cytokines
the investigators will dose a set of of pro-inflammatory and anti-inflammatory cytokines in the serum, namely interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and interferon (IFN).
Time frame: Single evaluation at baseline
Time Up and Go test
Time Up and Go test (continuous variable with units of measurement: second)
Time frame: Single evaluation at baseline
Inertial Gait Analysis
Gait analysis performed Inertial Measeurement Units to assess spatio-temporal variables ( continuous variables: m/s)
Time frame: Single evaluation at baseline
Inertial Gait Analysis
Gait analysis performed Inertial Measeurement Units to assess trunk acceleration-derived gait indexes ( continuous variables without measure unit)
Time frame: Single evaluation at baseline
5 Sit to Stand Test
Sit to Stand Test (continuous variable with units of measurement: second)
Time frame: Single evaluation at baseline
Hand Grip Test
Hand Grip Test (continuous variable with units of measurement: N)
Time frame: Single evaluation at baseline
Incremental Maximal Test
Peak oxygen consumption (continuous variable with units of measurement: ml/kg/min)
Time frame: Single evaluation at baseline
Geriatric depression scale-30
Geriatric depression scale-30 (continuous variable, score ranging from 0 to 30 with higher scores indicating more severe depression)
Time frame: Single evaluation at baseline
The Parkinson's Disease Questionnaire PDQ-39
Parkinson's Disease Questionnaire (continuous variable, score ranging from 0 to 156 with higher scores indicating more severe disability)
Time frame: Single evaluation at baseline
Brief Pain Inventory (BPI)
Brief Pain Inventory (BPI) (continuous variable, score ranging from 0 to 10 with higher scores indicating more severe disability)
Time frame: Single evaluation at baseline
King's PD pain scale (KPPS)
King's PD pain scale (KPPS) (continuous variable, score ranging from 0 to 168 with higher scores indicating more severe pain)
Time frame: Single evaluation at baseline
Pain Detect
Pain Detect (continuous variable, score ranging from -1 to 38 with higher scores indicating a more probable neurotic pain)
Time frame: Single evaluation at baseline
Peak work rate
Peak work rate (continuous variable with units of measuremente: w)
Time frame: Single evaluation at baseline
Peak heart rate
Peak heart rate (continuous variable with units of measuremente: b/min)
Time frame: Single evaluation at baseline
Gas exchange threshold
Gas exchange threshold (continuous variable with units of measuremente: l/min)
Time frame: Single evaluation at baseline
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IRCCS National Neurological Institute "C. Mondino" Foundation