NCT05815524

Physical Activity in Patients With Parkinson's Disease: a "Disease Modifying" Intervention?

Terminated NA Last updated 2 September 2025

What this trial tests

NA trial testing Physical activity training in Parkinson Disease in 30 participants. Terminated before completion.

Timeline

2 May 2022

Primary endpoint
31 December 2024

31 December 2024

Quick facts

Lead sponsor	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Phase	NA
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	other
Enrollment	30
Start date	2 May 2022
Primary completion	31 December 2024
Estimated completion	31 December 2024
Sites	1 location across Italy

Drugs / interventions tested

• Physical activity training

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Who can join

Adults 45 to 70, any sex, with Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigors, and tremor at rest. Distinctive neuropathological signs include progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and the presence of immunoreactive protein inclusions for α-syn, Lewy bodies (LB). The clinical phenotype is heterogeneous, both from a motor and non-motor point of view. Furthermore, the prognosis and response to drugs are highly variable and poorly predictable. To date, there are no biomarkers capable of early identification of clinical phenotypes and of predicting response to therapy. This constitutes a serious limit that probably represents one of the causes of the failure of the experimentation of the disease modifying therapies tested up to now (for example the anti-α-sin antibodies). Certainly, a deeper understanding of disease pathogenesis is needed to address these unsolved problems.

Oxidative stress and inflammation have critical roles in PD, especially in the prodromal and early stages of PD, as they contribute to pathological progression and also trigger potentially devastating neuroprotective responses, especially in the early stages. Consequently, soluble mediators of these processes may represent potential markers of prodromal phases of the disease.

Inflammation is a key factor in the initiation and propagation of a-syn aggregates and the contribution of microglial activation to a-syn pathology has been highlighted recently. Elevated a-syn specific T cell responses may be present years before the diagnosis of motor PD, suggesting a role of neuroinflammation in PD pathogenesis and early diagnosis. Furthermore, studies in rats overexpressing a-syn support the idea that reducing neuroinflammation could improve symptoms in early Parkinson's disease. In particular, drug-targeted anti-inflammatory approaches in a-syn rats prevent central and peripheral inflammation, as well as neuronal dysfunction and motor motor impairment.

It is also increasingly evident that panels that combine different biomarkers, with a multimodal approach, are more sensitive and specific, better reflecting the complexity of pathophysiological mechanisms. In fact, the diagnostic sensitivity of some CSF biomarker panels of neurodegeneration in distinguishing between atypical parkinsonisms and Parkinson's disease has been demonstrated. These markers, as well as in the cerebrospinal fluid, can be measured in the serum, albeit with reduced specificity, and in exosomes of central origin, which have recently been described and analyzed also in cohorts of patients with Parkinson's disease.

In addition to pharmacological approaches, attention has recently been paid to non-pharmacological therapeutic approaches, such as physical activity.

In particular, studies on PD patients show that aerobic exercise improves motor performance by increasing BDNF levels and reducing inflammation. Retrospective studies have found that moderate to vigorous exercise in midlife may protect against PD. In 2018, a phase 2 study investigated the response to treadmill exercise performed at two different intensities (high and moderate) by de novo PD patients, reporting a beneficial effect of moderate treadmill exercise. Although aerobic exercise appears to be the most effective, several studies have used a variety of exercise programs to demonstrate options available for those who cannot physically perform aerobic exercise. In PD patients, physical activity also appears to have beneficial effects on cognition, mood, and sleep quality. Preclinical findings support the hypothesis that physical activity exerts its beneficial effect by increasing levels of BDNF and anti-inflammatory cytokines and inhibiting pro-inflammatory factors.

In this study the investigators will measure changes in clinical scales and biomarkers in patients who undergo either an intensive physical activity protocol or continue their routine sedentary life.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine.
   Sharma A, Yadav A, Nandy A, Ghatak S. · · 2024 · cited 40× · PMID 38931833 · DOI 10.3390/pharmaceutics16060709
2. Extracellular Vesicles as Biomarkers for Parkinson's Disease: How Far from Clinical Translation?
   Gualerzi A, Picciolini S, Bedoni M, Guerini FR, et al · · 2024 · cited 17× · PMID 38256215 · DOI 10.3390/ijms25021136
3. Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.
   Chen Z, Mao Z, Tang W, Shi Y, et al · · 2025 · cited 4× · PMID 41299782 · DOI 10.1186/s40035-025-00517-1