Parkinson Disease Clinical Trial
Official title:
Biomarkers of Rehabilitation Outcome in Patients With Parkinson's Disease: Effect of a Customized Protocol on Treadmill Training With and Without Augmented Virtual Reality Application, a Randomized Controlled Trial
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).
Status | Recruiting |
Enrollment | 60 |
Est. completion date | December 31, 2023 |
Est. primary completion date | December 1, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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) |
Country | Name | City | State |
---|---|---|---|
Italy | IRCCS Fondazione Don Gnocchi Firenze | Florence |
Lead Sponsor | Collaborator |
---|---|
University of Florence | Fondazione Don Carlo Gnocchi Onlus |
Italy,
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* Note: There are 22 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Mean changes in walking speed (intra-group and between-group comparisons). | Gait speed (m/s) will be measured at both comfortable and maximum speeds using the Optogait system (http://www.optogait.com/Gait-Phases). | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean changes in step length during walking (intra-group and between-group comparisons). | Right and left step length (m) will be measured at both comfortable and maximum speeds using the Optogait system (http://www.optogait.com/Gait-Phases). | T1 (end of treatment-8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in walking endurance assessed with the 6-Minutes Walking Test (6MWT) (intra-group and between-group comparisons). | The distance (m) walked in 6 minutes on a 30 meters walkway will be measured, indicating the greater distance, a better score | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in gait adaptability assessed by C-Gait application of C-Mill (intra-group and between-group comparisons) | Walking-adaptability task performance was defined as the percentage of correctly performed steps relative to the projected visual objects in 6 different tasks.
C-gait score for each task: Level×2×Performance (%) / 100. The overall assessment score was an average score based on average performance over the six walking-adaptability tasks at the higher level of difficulty, ranging from 0 (poor performance) to 8 (excellent performance). |
T1 (end of treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in freezing during walking assessed by the Freezing Of Gait Questionnaire (FOG-Q) (intra-group and between-group comparisons). | The FOG-Q includes 6 items that inquires about the subject's experiences of freezing during the previous week. Each item use a five-points ordinal scale, ranging from "0" (= absence of symptoms) to "4" (= more severe disturbance). Total score ranges from 0 to 24, and higher scores correspond to more severe freezing. | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in postural stability (intra-group and between-group comparisons) | Postural sway assessed with a dynamometric footplate (postural sway in quiet standing with opened/closed eyes).
Lower postural sway corresponds to better stability. |
T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in global cognitive functions assessed by the Montreal Cognitive Assessment (MoCA) (intra-group and between-group comparisons) | The MoCA test is used to assess global cognitive functions. A score superior to 18.58 is required for inclusion in the study (Aiello et al, 2021); parallel versions will be administered at different time points (Siciliano et al, 2019). Higher values correspond to better cognition, range of score 0-30. | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in global cognitive functions assessed by the Parkinson's disease-cognitive rating scale, italian version (PD-CRS) (intra-group and between-group comparisons) | The PD-CRS is a suitable tool to assess cognition in PD, it evaluates different domains and permits to obtain a cortical and a subcortical score:
sum of results in item 1,3,4,5,7,8,9 (range of score 0-104), represents the subcortical score; sum of results in item 2 and 6 (range of score 0-30), represents the cortical score. Higher scores correspond to better cognition |
T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in attention skills assessed by Trail Making Test A and B (TMTA and TMTB) (intra-group and between-group comparisons) | TMTA evaluates sustained attention and the visual search capacity, and TMTB evaluates divided attention.
For both tests A and B time and errors will be registered. Slowness and more errors are indicative of lower performances (No range of score). |
T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in executive functions as assessed by the Stroop Test (intra-group and between-group comparisons) | The Stroop test is used to assess executive functions (time and error interference effect).
Slowness and higher interference effect indicative of lower performances. (No range of score). |
T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in executive functions as assessed by the Symbol Digit oral version (intra-group and between-group comparisons) | Digit symbol is used for the assessment of attention and working memory. Range of score 0-110. Higher score indicative of better performance | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in functional mobility assessed by the Modified Parkinson Activity Scale (MPAS) (intra-group and between-group comparisons) | The MPAS scale evaluates motor skills in activities of daily living. Range of score 0-56; higher score indicative of better functional mobility. | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in functional mobility assessed by the Timed up and go test (TUG) (intra-group and between-group comparisons) | The TUG is a general physical performance test used to assess mobility, balance, and gait during walking, turning, and sit-to-stand tasks.
Time is recorded during the test; less time indicative of better performances (no range of score). |
T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in functional autonomy assessed by the modified Barthel Index (mBI) (intra-group and between-group comparisons) | mBI is a scale for assessing functional independence in daily life. Range of score 0-100. Lower score corresponds to less independence. | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in the quality of life assessed by the Parkinson's Disease Questionnaire Italian version (PDQ-39-IT) (intra-group and between-group comparisons) | PDQ-39 is a self-report questionnaire for assessing the quality of daily life in PD. It includes 39 items assessing how often persons experience difficulty across 8 quality of life dimensions. Each item is scored on a five-point ordinal scale from 0 (=never) to 4 (always). Each dimension total score ranges from 0 (never have difficulty) to 100 (always have difficulty). The summary total score is calculated as the mean of the 8 dimension total scores. A higher score corresponds to a lower quality of life. | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in the fear to fall assessed by the Falls efficacy scale, Italian version (FES-I) (intra-group and between-group comparisons) | FES-I is used for the assessment of the fear-of-fall. It includes 16 items rated on a four-point scale from 1 (not confident at all) to 4 (completely confident). Total score ranges from minimum 16 (no concern about falling) to maximum 64 (severe concern about falling). | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in mood assessed by the Beck Depression Inventory II, italian version (BDI) (intra-group and between-group comparisons) | BDI II is used for the assessment of mood and consists of 21 items, each of whom corresponding to a symptom of depression. Each item is scored on a scale of 0-3 in a list of four statements arranged in increasing severity. Total score ranges from 0 to 63; higher scores indicates more severe depression. | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in pain perception assessed by the Numerical rating scale (NRS) (intra-group and between-group comparisons) | NRS is suitable for the assessment of current pain severity as perceived by the participant using a 0-10 points scale. A score of 10 corresponds to the worst pain. | T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Mean change in number and severity of falls assessed by the Falls Questionnaire (intra-group and between-groups comparisons) | Falls Questionnaire is used for the assessment of the frequency and severity of falls.
It provides information on the modality of falls and the number of falls in the last 12 months. A superior number of falls suggests a lower balance (no range of score). |
T0 (baseline); T1 (end of the treatment - 8 weeks); T2 (3 months after the end of treatment) | |
Other | Perception of satisfaction to the treatment assessed with a subjective satisfaction questionnaire- 5 point Likert scale | A 5 points Likert scale is useful to assess subjective satisfaction from 0 (minimum) to 5 (maximum) | T1 (end of the treatment - 8 weeks) | |
Primary | 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) | |
Primary | 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 | Correlation between Raman spectra of blood cEVs and primary outcomes after patient stratification | The biological characterization of patients at T0 analyzing cEVs performed by Raman Spectroscopy will provide numerical scores that will be correlated with motor parameters obtained at T1 to identify predictive biomarkers of an outcome measure of rehabilitation | T0 (baseline); T1 (end of the treatment - 8 weeks) | |
Secondary | Changes in individual Raman spectra of blood-derived cEVs before and after treatment | The Raman spectrum of blood-derived cEVs before and after treatment will be compared to identify spectral differences and to monitor the effect of rehabilitation on the spectral biomarker. Changes in the presence/absence of peaks and peaks intensity will be evaluated. | T0 (baseline); T1 (end of the treatment - 8 weeks) |
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