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

NCT07434089 | Recruiting

• 1 other identifier: GM-REHAB-2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (12)

• Relative abundance of bacterial and fungal taxa in fecal samples

  Relative abundance of bacterial and fungal taxa determined by sequencing the V3-V4 regions of the 16S rRNA and ITS1-IT2 regions from fecal samples. Unit of measurement: percentage of total sequencing reads(%).

  From enrollment to the 3 months follow-up

• Alpha Diversity of the Gut Microbiota

  Within-sample microbial diversity derived from sequencing of the V3-V4 regions of the 16S rRNA gene and ITS1-ITS2 regions from fecal samples, expressed as an alpha diversity index. Unit of Measure: alpha diversity index value. Higher values indicate greater microbial diversity.

  From enrollment to the 3 months follow-up

• Beta Diversity of the Gut Microbiota

  Between-sample microbial community derived from the sequencing of V3-V4 regions of the 16S rRNA and ITS1-ITS2 and expressed as a beta diversity distance. Unit of Measure: beta diversity distance. Higher values indicate greater dissimilarity between samples.

  From enrollment to the 3 months follow-up

• Distance Covered During the 6-Minute Walk Test

  Functional walking capacity measured as the total distance walked during the 6-Minute Walk Test. Unit of Measure: meters. Higher values indicate better walking capacity.

  From enrollment to the 3 months follow-up

• Time Required to Complete the 10-Meter Walk Test

  Walking ability assessed by measuring the time required to walk 10 meters at usual pace. Unit of Measure: seconds. Lower values indicate better walking performance.

  From enrollment to the 3 months follow-up

• Time Required to Complete the Timed Up and Go Test

  Mobility and fall risk assessed by the time needed to stand up, walk 3 meters, turn, return, and sit down. Unit of Measure: seconds. Lower values indicate better functional mobility.

  From enrollment to the 3 months follow-up

• Balance Performance Assessed by the Berg Balance Scale

  Balance measured using the Berg Balance Scale (range: 0-56). Higher scores indicate better balance and lower fall risk. Unit of Measure: total score.

  From enrollment to the 3 months follow-up

• Balance and Gait Performance Assessed by the Tinetti Scale

  Balance and gait evaluated using the Tinetti Scale (range: 0-29). Higher scores indicate better mobility and lower fall risk. Unit of Measure: total score.

  From enrollment to the 3 months follow-up

• Fear of Falling Assessed by the Short Falls Efficacy Scale-International

  Concern about falling measured using the Short Falls Efficacy Scale-International (range: 7-28). Higher scores indicate greater fear of falling. Unit of Measure: total score.

  From enrollment to the 3 months follow-up

• Motor Symptom Severity Assessed by the MDS-UPDRS Part III (Motor Examination)

  Motor impairment evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, the Motor Examination section. Total score range from 0 to 132. Unit of Measure: total score. Higher scores indicate worse motor impairment.

  From enrollment to the 3 months follow-up

• Functional Independence Assessed by the Functional Independence Measure

  Global functional status assessed using the Functional Independence Measure (range: 18-126). Higher scores indicate greater independence in daily activities. Unit of Measure: total score.

  From enrollment to the 3 months follow-up

• Severity of Constipation Assessed by the Constipation Scoring System

  Constipation severity measured using the Constipation Scoring System questionnaire (range: 0-30). Higher scores indicate more severe constipation. Unit of Measure: total score.

  From enrollment to the 3 months follow-up

Secondary Outcomes (10)

• Serum Concentration of TNF-α

  From enrollment to the 3 months follow-up

• Serum Concentration of IL-1β

  From enrollment to the 3 months follow-up

• Serum Concentration of IL-6

  From enrollment to the 3 months follow-up

• Serum Concentration of IL-10

  From enrollment to the 3 months follow-up

• Serum Concentration of IL-4

  From enrollment to the 3 months follow-up

Study Arms (3)

C-mill + VR treated

EXPERIMENTAL

includes 20 patients with PD undergoing C-Mill treatment combined with semi-immersive virtual reality (VR). This group will participate in 12 training sessions, each lasting 45 minutes, four times a week for three weeks. Gait training in each session will include exercises such as path with obstacles, tandem walking, slalom, and walking at varying speeds, all enhanced with semi-immersive VR scenarios projected on the treadmill's floor. 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 technology treadmill equipped with semi-immersive VR

C-Mill treated

EXPERIMENTAL

Consists of 20 patients with Parkinson's Disease (PD) undergoing C-Mill treatment as a standalone therapy, without the integration of virtual reality (VR). Participants will complete 12 training sessions, each lasting 45 minutes, four times a week for three weeks. The training sessions will include exercises such as tandem walking, slalom walking, obstacle courses, and walking at varying speeds, all designed to enhance gait and balance.

Device: C-Mill treatment without semi-immersive virtual reality (VR)

Conventional physiotherapy treated

EXPERIMENTAL

Consists of 20 patients with PD, who will undergo conventional physiotherapy training 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. Gait training will incorporate obstacle courses (e.g., bricks, boxes) of varying shapes and colors, or paths created by the physiotherapist using furniture and equipment (e.g., chairs, traffic cones, sandbags). Patients will also perform slalom walking exercises, with auditory stimuli (e.g., music, therapist's voice) and visual cues (e.g., colored tape on the floor) to guide the exercises, adjusting their walking speed based on the auditory cues provided by the therapist.

Other: Conventional physiotherapy training

Interventions

C-Mill technology treadmill equipped with semi-immersive VR DEVICE

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.

C-mill + VR treated

C-Mill treatment without semi-immersive virtual reality (VR) DEVICE

C-Mill treatment will be administrated as a standalone therapy, without the integration of virtual reality (VR).

C-Mill treated

Conventional physiotherapy training OTHER

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.

Conventional physiotherapy treated

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS Centro Neurolesi Bonino Pulejo: lead
• Università degli studi di Messina: collaborator

Study Sites (1)

Irccs Centro Neurolesi Bonino Pulejo

Messina, Messina, 98123, Italy

RECRUITING

Related Publications (16)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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. eCollection 2024.

  PMID: 39149144 BACKGROUND

• Frazzitta G, Ferrazzoli D, Folini A, Palamara G, Maestri R. Severe Constipation in Parkinson's Disease and in Parkinsonisms: Prevalence and Affecting Factors. Front Neurol. 2019 Jun 18;10:621. doi: 10.3389/fneur.2019.00621. eCollection 2019.

  PMID: 31275225 BACKGROUND

• Fayyaz M, Jaffery SS, Anwer F, Zil-E-Ali A, Anjum I. The Effect of Physical Activity in Parkinson's Disease: A Mini-Review. Cureus. 2018 Jul 18;10(7):e2995. doi: 10.7759/cureus.2995.

  PMID: 30245949 BACKGROUND

• Yu QJ, Yu SY, Zuo LJ, Lian TH, Hu Y, Wang RD, Piao YS, Guo P, Liu L, Jin Z, Li LX, Chan P, Chen SD, Wang XM, Zhang W. Parkinson disease with constipation: clinical features and relevant factors. Sci Rep. 2018 Jan 12;8(1):567. doi: 10.1038/s41598-017-16790-8.

  PMID: 29330419 BACKGROUND

• Cataldi S, Bonavolonta V, Poli L, Clemente FM, De Candia M, Carvutto R, Silva AF, Badicu G, Greco G, Fischetti F. The Relationship between Physical Activity, Physical Exercise, and Human Gut Microbiota in Healthy and Unhealthy Subjects: A Systematic Review. Biology (Basel). 2022 Mar 21;11(3):479. doi: 10.3390/biology11030479.

  PMID: 35336852 BACKGROUND

• Gao X, Zhang P. Exercise perspective: Benefits and mechanisms of gut microbiota on the body. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 Apr 28;49(4):508-515. doi: 10.11817/j.issn.1672-7347.2024.230550. Chinese, English.

  PMID: 39019779 BACKGROUND

• Mach N, Fuster-Botella D. Endurance exercise and gut microbiota: A review. J Sport Health Sci. 2017 Jun;6(2):179-197. doi: 10.1016/j.jshs.2016.05.001. Epub 2016 May 10.

  PMID: 30356594 BACKGROUND

• Sohail MU, Yassine HM, Sohail A, Thani AAA. Impact of Physical Exercise on Gut Microbiome, Inflammation, and the Pathobiology of Metabolic Disorders. Rev Diabet Stud. 2019;15:35-48. doi: 10.1900/RDS.2019.15.35. Epub 2019 Aug 4.

  PMID: 31380886 BACKGROUND

• Gubert C, Kong G, Renoir T, Hannan AJ. Exercise, diet and stress as modulators of gut microbiota: Implications for neurodegenerative diseases. Neurobiol Dis. 2020 Feb;134:104621. doi: 10.1016/j.nbd.2019.104621. Epub 2019 Oct 16.

  PMID: 31628992 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 13, 2026
• First Posted: February 25, 2026
• Study Start: October 20, 2025
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): October 20, 2028
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

IT (1)