Impact of C-Mill Rehabilitation on the Gut-Brain Axis in Parkinson's Disease

Official title

Gut-Brain Axis and Rehabilitation: Study on the Effects of C-Mill Technology on the Intestinal Microbiota of Parkinson's Disease Patients

Overview

The GM-REHAB-2025 study aims to evaluate the impact of physiotherapy interventions using the C-Mill treadmill, with and without semi-immersive virtual reality, on gut microbiota and metabolic parameters in patients with Parkinson's disease. Three groups will be involved: one undergoing conventional physiotherapy, one treated with the C-Mill without virtual reality (VR), and one treated with C-Mill technology combined with VR. Clinical assessments and the collection of biological samples (stool, serum, and plasma) will be carried out at three time points: at baseline, at the end of treatment (21 days), and after 3 months.

Interventions

• Device C-Mill technology treadmill equipped with semi-immersive VR
  C-Mill treatment combined with semi-immersive virtual reality (VR). The VR component will feature visual obstacles, such as virtual traffic cones or country paths, in conjunction with audio-visual stimuli to promote engagement and guide movement.
• Device C-Mill treatment without semi-immersive virtual reality (VR)
  C-Mill treatment will be administrated as a standalone therapy, without the integration of virtual reality (VR).
• Other Conventional physiotherapy training
  Will be carried under the manual guidance and supervision of a physiotherapist. The rehabilitation program will include weight-shifting exercises, as well as monopodal and bipodal balance exercises.

Primary outcome measures

• Relative abundance of bacterial and fungal taxa in fecal samples [Time frame: From enrollment to the 3 months follow-up]
• Alpha Diversity of the Gut Microbiota [Time frame: From enrollment to the 3 months follow-up]
• Beta Diversity of the Gut Microbiota [Time frame: From enrollment to the 3 months follow-up]
• Distance Covered During the 6-Minute Walk Test [Time frame: From enrollment to the 3 months follow-up]
• Time Required to Complete the 10-Meter Walk Test [Time frame: From enrollment to the 3 months follow-up]
• Time Required to Complete the Timed Up and Go Test [Time frame: From enrollment to the 3 months follow-up]
• Balance Performance Assessed by the Berg Balance Scale [Time frame: From enrollment to the 3 months follow-up]
• Balance and Gait Performance Assessed by the Tinetti Scale [Time frame: From enrollment to the 3 months follow-up]
• Fear of Falling Assessed by the Short Falls Efficacy Scale-International [Time frame: From enrollment to the 3 months follow-up]
• Motor Symptom Severity Assessed by the MDS-UPDRS Part III (Motor Examination) [Time frame: From enrollment to the 3 months follow-up]

Secondary outcome measures (10)

• Serum Concentration of TNF-α [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of IL-1β [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of IL-6 [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of IL-10 [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of IL-4 [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of FNDC5 [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of Adiponectin [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of Reduced Glutathione [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of Oxidized Glutathione [Time frame: From enrollment to the 3 months follow-up]
• Serum Concentration of High-Sensitivity C-Reactive Protein [Time frame: From enrollment to the 3 months follow-up]

Eligibility criteria

Inclusion criteria

• Diagnosis of PD according to the Movement Disorder Society Clinical
• Diagnostic Criteria for Parkinson's Disease
• Age comprised between 40 to 70 years
• Patients with moderate to advanced disease (2 ≤ Hoehn and Yahr classification grade ≤ 4)
• Individuals able to walk independently (FAC > 2)

Exclusion criteria

• PD patients with (1) weight > 135 kg and Height > 200 cm
• Open lesions or bandages whether in contact with the harness of C-Mill strumentation
• chronic gastro-intestinal (GI) disease including malabsorption;
• clinical history of gastric lesions, gastro-resection or major intestinal surgery;
• systemic and/or neurologic infectious, inflammatory, or autoimmune diseases of gastro-intestinal (GI) eg. Chron disease;
• Acute GI phlogosis or GI disease in the last 4 weeks before recruitment;
• Use of domperidone, or any drug potentially affecting gastrointestinal motility and integrity;
• Use, in the last 4 weeks preceding the recruitment and until t2, of pre-probiotics or therapy based upon steroids, nonsteroidal anti-inflammatory drugs, antibiotics or antifungals;
• anamnesis suggestive of GI cancer pathology.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Health services research

Study locations

Italy · 1 center

• Irccs Centro Neurolesi Bonino Pulejo — Messina

Publications

• Pullia M, Ciatto L, Andronaco G, Donato C, Aliotta RE, Quartarone A, De Cola MC, Bonanno M, Calabro RS, Cellini R. Treadmill Training Plus Semi-Immersive Virtual Reality in Parkinson's Disease: Results from a Pilot Study. Brain Sci. 2023 Sep 12;13(9):1312. doi: 10.3390/brainsci13091312. PMID 37759913
• Malik AN, Tariq H, Afridi A, Rathore FA. Technological advancements in stroke rehabilitation. J Pak Med Assoc. 2022 Aug;72(8):1672-1674. doi: 10.47391/JPMA.22-90. PMID 36280946
• Dockx K, Bekkers EM, Van den Bergh V, Ginis P, Rochester L, Hausdorff JM, Mirelman A, Nieuwboer A. Virtual reality for rehabilitation in Parkinson's disease. Cochrane Database Syst Rev. 2016 Dec 21;12(12):CD010760. doi: 10.1002/14651858.CD010760.pub2. PMID 28000926
• Mayer EA, Tillisch K. The brain-gut axis in abdominal pain syndromes. Annu Rev Med. 2011;62:381-96. doi: 10.1146/annurev-med-012309-103958. PMID 21090962
• Drossman DA, Tack J, Ford AC, Szigethy E, Tornblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology. 2018 Mar;154(4):1140-1171.e1. doi: 10.1053/j.gastro.2017.11.279. Epub 2017 Dec 22. PMID 29274869
• Trindade MFD, Viana RA. Effects of auditory or visual stimuli on gait in Parkinsonic patients: a systematic review. Porto Biomed J. 2021 Aug 4;6(4):e140. doi: 10.1097/j.pbj.0000000000000140. eCollection 2021 Jul-Aug. PMID 34368491
• Mak MKY, Wong-Yu ISK. Exercise for Parkinson's disease. Int Rev Neurobiol. 2019;147:1-44. doi: 10.1016/bs.irn.2019.06.001. Epub 2019 Jun 27. PMID 31607351
• Tang X, Huang Z, Zhu G, Liang H, Sun H, Zhang Y, Tan Y, Cui M, Gong H, Wang X, Chen YH. Matching supplementary motor area-primary motor cortex paired transcranial magnetic stimulation improves motor dysfunction in Parkinson's disease: a single-center, double-blind randomized controlled clinical trial protocol. Front Aging Neurosci. 2024 Aug 1;16:1422535. doi: 10.3389/fnagi.2024.1422535. eCollectio PMID 39149144

Identifiers

NCT: NCT07434089 · GM-REHAB-2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗