NCT06977204: MOVE-ON_WP1

Physical Activity on Neuroinflammation in Parkinson's Disease

Recruiting now Last updated 18 May 2025

What this trial tests

trial in Parkinson Disease in 40 participants. Currently enrolling.

Timeline

1 January 2023

Primary endpoint
31 December 2025

1 June 2026

Quick facts

Lead sponsor	IRCCS National Neurological Institute "C. Mondino" Foundation
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	40
Start date	1 January 2023
Primary completion	31 December 2025
Estimated completion	1 June 2026
Sites	1 location across Italy

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →
• Physical Inactivity — all drugs for Physical Inactivity →
• Physical Disability — all drugs for Physical Disability →

Sponsor

IRCCS National Neurological Institute "C. Mondino" Foundation

Who can join

Adults 40 to 80, any sex, with Parkinson Disease or Physical Inactivity. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.