Effect of a Progressive Treadmill Training Protocol for Parkinson's Disease

NCT05902065 | Unknown

• 1 other identifier: VIRTREAD-PD
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this single-center, no-profit, longitudinal interventional randomized controlled, single-blind trial is to compare the effects of 2 different treadmill training treatments using C-Mill: the experimental one, endowed with augmented virtual reality (AVR) applications, versus the conventional one, the standard treadmill training in PD patients with gait and or balance disturbances. The main questions the study aims to answer are 1) Is the experimental treatment more effective than the conventional one? 2) Is it possible to identify predictive and indicative biomarkers of an outcome measure of rehabilitation using extracellular vesicles (cEVs) assessed by Raman spectroscopy? Participants will be randomized into two groups: the experimental group that will receive the experimental intervention, and the control group that will receive the conventional intervention. Both groups will train three times per week for 8 weeks, the first session starting from 25 minutes (25'). The experimental and the conventional treatments are planned to be progressive and will be individualized to the participant's level of performance. Clinical, neuropsychological, and instrumental variables will be collected at baseline (T0), at the end of the treatment (T1), and 3 months after the end of treatment (T2). At 6 months after the end of treatment (T3), a phone interview will be performed. Both within-group and between-group analyses will be conducted. Biosamples will be collected at baseline (T0) and at the end of treatment (T1).

Conditions

Parkinson Disease; Gait, Festinating; Fall Due to Loss of Equilibrium; Gait, Unsteady; Gait, Shuffling

Keywords

Parkinson Disease; Gait rehabilitation; Balance; Falls; Physiotherapy; Rehabilitation; Biomarkers; Raman spectroscopy; extracellular vesicles

Outcome Measures

Primary Outcomes (2)

• Mean change in gait and balance parameters assessed by the Performance Oriented Mobility Assessment - POMA scale (intra-group and between-group comparisons)

  The POMA scale is an easily administered task-oriented test that measures an older adult's balance (9 items) and gait (7 items) abilities. Items are scored with a three-point (0-2) or a two points (0-1) scale, where "0" indicates the highest level of impairment and "2" - "1" for dichotomic items - the individual's independence. Total Balance Score = 16; Total Gait Score = 12.

  T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment)

• Mean change in motors parameters assessed by the Modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS), part III (intra-group and between-group comparisons)

  The MDS-UPDRS part III includes 18 items concerning the motor examination in PD, evaluating different aspects: walking, balance, speech, bradykinesia, tremor, and rigidity. Each item is scored on a five-point ordinal rating scale, ranging from 0 to 4, where "0" indicates normal function and "4" is the highest level of impairment. Some items inclusive of evaluation of a symptom in different parts of the body, e.g on the right side, on the left side, upper and lower limbs). Score range 0-132.

  T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment)

Secondary Outcomes (2)

• Correlation between Raman spectra of blood cEVs and primary outcomes after patient stratification

  T0 (baseline); T1 (end of the treatment - 8 weeks)

• Changes in individual Raman spectra of blood-derived cEVs before and after treatment

  T0 (baseline); T1 (end of the treatment - 8 weeks)

Other Outcomes (20)

• Mean changes in walking speed (intra-group and between-group comparisons).

  T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment)

• Mean changes in step length during walking (intra-group and between-group comparisons).

  T1 (end of treatment-8 weeks); T2 (3 months after the end of treatment)

• Mean change in walking endurance assessed with the 6-Minutes Walking Test (6MWT) (intra-group and between-group comparisons).

  T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment)

Study Arms (2)

AVR Treadmill training with C-Mill

EXPERIMENTAL

Participants (N=30) will undergo the AVR Treadmill training intervention with 5 AVR applications named "Nature Island", "stepping stones", "walking area": "obstacles avoidance", and "track".

Device: AVR Treadmill training with C-Mill

Conventional Treadmill training with C-Mill

ACTIVE COMPARATOR

Participants (N=30) will undergo the "Traditional Treadmill" intervention.

Device: Conventional Treadmill training with C-Mill

Interventions

AVR Treadmill training with C-Mill DEVICE

The protocol will include three sessions per week for 8 weeks of gait training using C-Mill with AVR applications. An anchoring system will prevent possible falls, activities will be stopped on patient request, or when a heart rate considered safe will be exceeded. The patient will be supervised by a physical therapist and asked not to use lateral bars. Treatment is planned to be progressive and will be individualized to the participant's level of performance. Progression in gait speed: at the training start, gait speed will be set at 80% of the individual's overground walking speed and weekly increased by 10%, to a maximum of 120%; progression in trial duration: at the training start the duration will be set at 25' and every two weeks increased by 5'; the maximum duration of a session will reach 45'; progression in difficulty: the protocol has 5 levels for each AVR application, and the transition among levels will be set at 80% success achievement.

AVR Treadmill training with C-Mill

Conventional Treadmill training with C-Mill DEVICE

The protocol will include three sessions per week for 8 weeks of gait training using C-Mill without AVR applications, walking on the treadmill. An anchoring system will prevent possible falls, activities will be stopped on patient request, or when a heart rate considered safe will be exceeded. All sessions will be supervised by a physical therapist, who will give guidance and standardized cues on walking patterns (e.g., step length). The patient will be asked not to use the lateral bars. Treatment is planned to be progressive and will be individualized to the participant's level of performance: progression in gait speed: at the training start, gait speed will be set at 80% of the individual's overground walking speed and weekly increased by 10%, to a maximum of 120%; progression in trial duration: at the training start the duration will be set at 25' and every two weeks increased by 5'; the maximum duration of a session will reach 45'.

Conventional Treadmill training with C-Mill

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Parkinson's disease according to the diagnostic (POSTUMA criteria)
• Hoehn and Yahr Stage II-III
• Age\>18 years
• One fall in the past 3 months/presence of postural instability /gait disturbance
• Able to walk for at least 5 minutes without assistance
• Stable drug therapy by at least 1 month
• Willingness to participate in the study, ability to understand and willingness to sign informed consent

You may not qualify if:

• Other pathology concurrent with gait disturbance (symptomatic arthritis involving hip/knee/ankle, stroke outcomes, severe polyneuropathy)
• Cognitive impairment capable of interfering with rehabilitation procedures, estimated as a score less than 18.58 at the Montreal Cognitive Assessment (MoCA), row score corrected according to Aiello et al, 2022
• Hallucinations
• Psychiatric disorder not controlled by current drug therapy
• Alcohol/drug use
• Uncompensated visual/auditory deficit that limits enjoyment of the cues provided by the AVR
• Communication deficit from any cause that impairs understanding of the task and the objectives of the intervention
• Recurrent episodes of severe orthostatic hypotension
• Severe cardiovascular diseases
• Patient undergoing other experimental protocol (patients regularly undergoing physical activity or sport will not be excluded)

Sponsors & Collaborators

• University of Florence: lead
• Fondazione Don Carlo Gnocchi Onlus: collaborator

Study Sites (1)

IRCCS Fondazione Don Gnocchi Firenze

Florence, 50100, Italy

RECRUITING

Related Publications (22)

• Gualerzi A, Picciolini S, Carlomagno C, Terenzi F, Ramat S, Sorbi S, Bedoni M. Raman profiling of circulating extracellular vesicles for the stratification of Parkinson's patients. Nanomedicine. 2019 Nov;22:102097. doi: 10.1016/j.nano.2019.102097. Epub 2019 Oct 21.

  PMID: 31648040 BACKGROUND

• Erdfelder, E., Faul, F., & Buchner, A. (1996). GPOWER: A general power analysis program. Behavior research methods, instruments, & computers, 28(1), 1-11.

  BACKGROUND

• Ganesan M, Sathyaprabha TN, Gupta A, Pal PK. Effect of partial weight-supported treadmill gait training on balance in patients with Parkinson disease. PM R. 2014 Jan;6(1):22-33. doi: 10.1016/j.pmrj.2013.08.604. Epub 2013 Sep 8.

  PMID: 24021298 BACKGROUND

• Tinetti ME. Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc. 1986 Feb;34(2):119-26. doi: 10.1111/j.1532-5415.1986.tb05480.x. No abstract available.

  PMID: 3944402 BACKGROUND

• Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.

  PMID: 19025984 BACKGROUND

• Tambasco N, Simoni S, Eusebi P, Ripandelli F, Brahimi E, Sacchini E, Nigro P, Marsili E, Calabresi P. The validation of an Italian version of the Freezing of Gait Questionnaire. Neurol Sci. 2015 May;36(5):759-64. doi: 10.1007/s10072-014-2037-5. Epub 2014 Dec 17.

  PMID: 25515786 BACKGROUND

• Downie WW, Leatham PA, Rhind VM, Wright V, Branco JA, Anderson JA. Studies with pain rating scales. Ann Rheum Dis. 1978 Aug;37(4):378-81. doi: 10.1136/ard.37.4.378.

  PMID: 686873 BACKGROUND

• Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991 Feb;39(2):142-8. doi: 10.1111/j.1532-5415.1991.tb01616.x.

  PMID: 1991946 BACKGROUND

• Keus SH, Nieuwboer A, Bloem BR, Borm GF, Munneke M. Clinimetric analyses of the Modified Parkinson Activity Scale. Parkinsonism Relat Disord. 2009 May;15(4):263-9. doi: 10.1016/j.parkreldis.2008.06.003. Epub 2008 Aug 8.

  PMID: 18691929 BACKGROUND

• Galeoto G, Colalelli F, Massai P, Berardi A, Tofani M, Pierantozzi M, Servadio A, Fabbrini A, Fabbrini G. Quality of life in Parkinson's disease: Italian validation of the Parkinson's Disease Questionnaire (PDQ-39-IT). Neurol Sci. 2018 Nov;39(11):1903-1909. doi: 10.1007/s10072-018-3524-x. Epub 2018 Aug 7.

  PMID: 30088166 BACKGROUND

• Ruggiero C, Mariani T, Gugliotta R, Gasperini B, Patacchini F, Nguyen HN, Zampi E, Serra R, Dell'Aquila G, Cirinei E, Cenni S, Lattanzio F, Cherubini A. Validation of the Italian version of the falls efficacy scale international (FES-I) and the short FES-I in community-dwelling older persons. Arch Gerontol Geriatr. 2009;49 Suppl 1:211-9. doi: 10.1016/j.archger.2009.09.031.

  PMID: 19836635 BACKGROUND

• Molino-Lova R, Sofi F, Pasquini G, Gori A, Vannetti F, Abbate R, Gensini GF, Macchi C; Mugello Study Working Group. The Mugello study, a survey of nonagenarians living in Tuscany: design, methods and participants' general characteristics. Eur J Intern Med. 2013 Dec;24(8):745-9. doi: 10.1016/j.ejim.2013.09.008. Epub 2013 Oct 11.

  PMID: 24125724 BACKGROUND

• Ghisi M at al 2006, Beck Depression Inventory - II (BDI-II) Manuale. Firenze: O.S. Organizzazioni Speciali

  BACKGROUND

• Santangelo G, Barone P, Abbruzzese G, Ferini-Strambi L, Antonini A; IRIS Study Group. Validation of the Italian version of Parkinson's disease-cognitive rating scale (PD-CRS). Neurol Sci. 2014 Apr;35(4):537-44. doi: 10.1007/s10072-013-1538-y. Epub 2013 Sep 25.

  PMID: 24221858 BACKGROUND

• Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E. Trail making test: normative values from 287 normal adult controls. Ital J Neurol Sci. 1996 Aug;17(4):305-9. doi: 10.1007/BF01997792.

  PMID: 8915764 BACKGROUND

• Nocentini U, Giordano A, Di Vincenzo S, Panella M, Pasqualetti P. The Symbol Digit Modalities Test - Oral version: Italian normative data. Funct Neurol. 2006 Apr-Jun;21(2):93-6.

  PMID: 16796824 BACKGROUND

• Aiello EN, Gramegna C, Esposito A, Gazzaniga V, Zago S, Difonzo T, Maddaluno O, Appollonio I, Bolognini N. The Montreal Cognitive Assessment (MoCA): updated norms and psychometric insights into adaptive testing from healthy individuals in Northern Italy. Aging Clin Exp Res. 2022 Feb;34(2):375-382. doi: 10.1007/s40520-021-01943-7. Epub 2021 Jul 27.

  PMID: 34313961 BACKGROUND

• Chen ZY, Yan HJ, Qi L, Zhen QX, Liu C, Wang P, Liu YH, Wang RD, Liu YJ, Fang JP, Su Y, Yan XY, Liu AX, Xi J, Fang B. C-Gait for Detecting Freezing of Gait in the Early to Middle Stages of Parkinson's Disease: A Model Prediction Study. Front Hum Neurosci. 2021 Mar 22;15:621977. doi: 10.3389/fnhum.2021.621977. eCollection 2021.

  PMID: 33828470 BACKGROUND

• Steffen T, Seney M. Test-retest reliability and minimal detectable change on balance and ambulation tests, the 36-item short-form health survey, and the unified Parkinson disease rating scale in people with parkinsonism. Phys Ther. 2008 Jun;88(6):733-46. doi: 10.2522/ptj.20070214. Epub 2008 Mar 20. Erratum In: Phys Ther. 2010 Mar;90(3):462.

  PMID: 18356292 BACKGROUND

• Siciliano M, Chiorri C, Passaniti C, Sant'Elia V, Trojano L, Santangelo G. Comparison of alternate and original forms of the Montreal Cognitive Assessment (MoCA): an Italian normative study. Neurol Sci. 2019 Apr;40(4):691-702. doi: 10.1007/s10072-019-3700-7. Epub 2019 Jan 14.

  PMID: 30637545 BACKGROUND

• Santangelo G, Lagravinese G, Battini V, Chiorri C, Siciliano M, Abbruzzese G, Vitale C, Barone P. The Parkinson's Disease-Cognitive Rating Scale (PD-CRS): normative values from 268 healthy Italian individuals. Neurol Sci. 2017 May;38(5):845-853. doi: 10.1007/s10072-017-2844-6. Epub 2017 Feb 21.

  PMID: 28224328 BACKGROUND

• Wang Y, Gao L, Yan H, Jin Z, Fang J, Qi L, Zhen Q, Liu C, Wang P, Liu Y, Wang R, Liu Y, Su Y, Liu A, Fang B. Efficacy of C-Mill gait training for improving walking adaptability in early and middle stages of Parkinson's disease. Gait Posture. 2022 Jan;91:79-85. doi: 10.1016/j.gaitpost.2021.10.010. Epub 2021 Oct 11.

  PMID: 34656008 BACKGROUND

Related Links

• gait parameters derived from Optogait assessment

MeSH Terms

Conditions

Parkinson Disease; Gait Disorders, Neurologic

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Francesca Cecchi, MD

CONTACT

00393388627184; francesca.cecchi@unifi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome Assessors will be blinded regarding treatment assignment, including clinicians assessing the eligibility of patients and enrolling them in the study; the evaluators (neurologist, physiatrist, psychologist, physical therapists, engineers, laboratory staff). Blindness will be ensured by the modality and timing of assessments at T0, T1, and T2 that will be conducted at times other than treatment and by evaluators not involved in the treadmill training. Blinding will be removed if requested by the participant at the end of the study and in case of undesirable effects.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Single-center, randomized controlled, single-blind trial with no-profit purpose.

Study Record Dates

• First Submitted: May 1, 2023
• First Posted: June 13, 2023
• Study Start: July 6, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 31, 2023
• Last Updated: June 13, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)