Physical Activity on Neuroinflammation in Parkinson's Disease

NCT06977204 | Recruiting

• 1 other identifier: MOVE-ON
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease; Physical Inactivity; Physical Disability

Keywords

Physical activity; Neurological disorder; Neuroinflammation

Outcome Measures

Primary Outcomes (1)

• 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).

  Single evaluation at baseline

Secondary Outcomes (14)

• Time Up and Go test

  Single evaluation at baseline

• Inertial Gait Analysis

  Single evaluation at baseline

• Inertial Gait Analysis

  Single evaluation at baseline

• 5 Sit to Stand Test

  Single evaluation at baseline

• Hand Grip Test

  Single evaluation at baseline

Study Arms (2)

PD-SPORT

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).

PD-SEDENTARY

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).

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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.

You may qualify if:

• Subjects of both sexes, aged between 40 and 80 years (extremes included)
• Diagnosis of Parkinson's disease according to the clinical diagnostic criteria of the Movement Disorder Society
• Hoehn \& Yahr between 1 and 3

You may not qualify if:

• Concomitant diagnosis of other neurological diseases
• Presence of confirmed cognitive decline (MMSE \< 24)
• Presence of depression with (BDI \> 40)
• Patients with deep brain stimulation implant or undergoing DuoDopa therapy
• Presence of significant diseases affecting the musculoskeletal system
• Presence of internal medicine conditions, considered clinically significant by the investigator
• Acute or recent infections
• Body Mass Index (BMI) \>= 30
• Active smoking behavior
• Ongoing treatment with N-acetylcysteine or anti-oxidants
• Pregnancy or lactation

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead

Study Sites (1)

IRCCS Mondino Foundation

Pavia, Pavia, 27100, Italy

RECRUITING

Related Publications (3)

• Szymura J, Kubica J, Wiecek M, Pera J. The Immunomodulary Effects of Systematic Exercise in Older Adults and People with Parkinson's Disease. J Clin Med. 2020 Jan 9;9(1):184. doi: 10.3390/jcm9010184.

  PMID: 31936624 BACKGROUND

• Xu J, He X, Xu Y, Chen X, Li M, Zhang L, Fu X, Pan M, Wang Q, Hu X. Characteristics of systemic inflammation and brain iron deposition in Parkinson's disease patients. Ann Clin Transl Neurol. 2022 Mar;9(3):276-285. doi: 10.1002/acn3.51512. Epub 2022 Jan 25.

  PMID: 35078271 BACKGROUND

• Pajares M, I Rojo A, Manda G, Bosca L, Cuadrado A. Inflammation in Parkinson's Disease: Mechanisms and Therapeutic Implications. Cells. 2020 Jul 14;9(7):1687. doi: 10.3390/cells9071687.

  PMID: 32674367 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Venous blood samples from the anticubital vein.

MeSH Terms

Conditions

Parkinson Disease; Sedentary Behavior; Motor Activity; Nervous System Diseases; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Behavior; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Roberto De Icco

CONTACT

+390382380425; roberto.deicco@mondino.it

Cinzia Fattore

CONTACT

+390382380385; cinzia.fattore@mondino.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 18, 2025
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Locations

IT (1)