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

February 20, 2026 updated by: Maria Lui, IRCCS Centro Neurolesi Bonino Pulejo

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Messina
      • Messina, Messina, Italy, 98123
        • Recruiting
        • IRCCS Centro Neurolesi Bonino Pulejo
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: C-mill + VR treated
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 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.
Experimental: C-Mill treated
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)
C-Mill treatment will be administrated as a standalone therapy, without the integration of virtual reality (VR).
Experimental: Conventional physiotherapy treated
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative abundance of bacterial and fungal taxa in fecal samples
Time Frame: From enrollment to the 3 months follow-up

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
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up
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)
Time Frame: From enrollment to the 3 months follow-up
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
Time Frame: From enrollment to the 3 months follow-up

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
Time Frame: From enrollment to the 3 months follow-up

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Concentration of TNF-α
Time Frame: From enrollment to the 3 months follow-up
Serum TNF-α, a key pro-inflammatory cytokine, measured by ELISA to assess systemic inflammatory activation. Unit of Measure: pg/mL
From enrollment to the 3 months follow-up
Serum Concentration of IL-1β
Time Frame: From enrollment to the 3 months follow-up
Serum IL-1β, a pro-inflammatory cytokine involved in immune response, measured by ELISA. Unit of Measure: pg/mL
From enrollment to the 3 months follow-up
Serum Concentration of IL-6
Time Frame: From enrollment to the 3 months follow-up
Serum IL-6, a pro-inflammatory cytokine that mediates systemic inflammation, measured by ELISA. Unit of Measure: pg/mL
From enrollment to the 3 months follow-up
Serum Concentration of IL-10
Time Frame: From enrollment to the 3 months follow-up
Serum IL-10, an anti-inflammatory cytokine that regulates immune responses, measured by ELISA. Unit of Measure: pg/mL
From enrollment to the 3 months follow-up
Serum Concentration of IL-4
Time Frame: From enrollment to the 3 months follow-up
Serum IL-4, an anti-inflammatory cytokine involved in immune modulation, measured by ELISA. Unit of Measure: pg/mL
From enrollment to the 3 months follow-up
Serum Concentration of FNDC5
Time Frame: From enrollment to the 3 months follow-up
Serum FNDC5, a metabolic peptide measured by ELISA. Unit of Measure: ng/mL
From enrollment to the 3 months follow-up
Serum Concentration of Adiponectin
Time Frame: From enrollment to the 3 months follow-up
Serum Adiponectin, a metabolic peptide measured by ELISA. Unit of Measure: ng/mL
From enrollment to the 3 months follow-up
Serum Concentration of Reduced Glutathione
Time Frame: From enrollment to the 3 months follow-up
Serum Reduced Glutathione (GSH), a key antioxidant reflecting oxidative stress status, measured by ELISA. Unit of Measure: µmol/L
From enrollment to the 3 months follow-up
Serum Concentration of Oxidized Glutathione
Time Frame: From enrollment to the 3 months follow-up
Serum Oxidized Glutathione (GSSG), the oxidized form of glutathione indicating oxidative stress, measured by ELISA. Unit of Measure: µmol/L
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
Serum High-Sensitivity C-Reactive Protein (hs-CRP), an acute-phase protein reflecting systemic inflammation, measured by ELISA. Unit of Measure: mg/L
From enrollment to the 3 months follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Centro Neurolesi Bonino Pulejo

Collaborators

Università degli studi di Messina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2025

Primary Completion (Estimated)

October 20, 2027

Study Completion (Estimated)

October 20, 2028

Study Registration Dates

First Submitted

February 13, 2026

First Submitted That Met QC Criteria

February 20, 2026

First Posted (Actual)

February 25, 2026

Study Record Updates

Last Update Posted (Actual)

February 25, 2026

Last Update Submitted That Met QC Criteria

February 20, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GM-REHAB-2025

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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