Effect of Cognitive Training on Gait in Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

Disorders of Gait, Postural Stability and Cognition in Parkinson's Disease: Presymptomatic Detection and Targeted Rehabilitation

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05514379
• Other study ID #: NU20-04-00327
• Status: Enrolling by invitation
• Phase: N/A
• Start date: October 1, 2022
• Est. completion date: December 2023

Study information

• Verified date: September 2023
• Source: General University Hospital, Prague
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Physiotherapy and targeted rehabilitation are routinely performed in order to influence disorders of posture, gait and stability in Parkinson´s disease (PD), but their effects have been controversial (Keus et al. 2014; Walton wt al. 2014). Recently, several studies suggested that cognitive training can improve gait in patients with PD (Peterson et al. 2016, Heremans et al. 2013), similar to the effects seen in the elderly (Yogev-Seligmann et al. 2008; Amboni et al. 2013). Specific training programs including dual tasking with automatic verbal series, counting etc. have led to increased walking speed and improved stepping cadence, length, and duration in patients with dementia (Schwenk et al. 2010). However, since in advanced PD patients dual-task gait training has to be supervised by therapists, it is not a suitable type of therapy to be performed at home. Therefore, this study aims to verify and extend the encouraging results of the single study which showed a positive effect of cognitive function training on gait in PD (Milman et al. 2014) by exploring this effect in advanced PD patients, by assessing the effect on gait using more targeted clinical and instrumental evaluation, and by comparing two modes of therapy delivery, group and computer-based.

Description:

• Background: In a pilot study, Milman et al. 2014 showed that computer-based cognitive training focusing on executive function and attention performed at home might improve selected gait parameters in early patients with Parkinson´s disease (PD).

• Goal 1: To explore this effect in advanced PD patients

• Hypothesis 1: Effect of cognitive training focusing on executive function and attention will be detected also in advanced PD patients and this effect will be larger as compared to the results published by Milman et al. 2014.

• Goal 2: To verify the results published by Milman et al. 2014 using more targeted clinical and instrumental gait assessment, including dual-task gait evaluation as well as instrumental testing of turn fluency (Bertoli et al. 2019).

• Hypothesis 2: The results published by Milman et al. 2014 will be confirmed and an effect on dual-task gait and turn fluency will be shown.

• Goal 3: To explore the role of the form of therapy setting, i.e. whether group setting might increase the effect of cognitive training on gait as compared to individual cognitive training at home. Such results have been shown in the case of a physiotherapy intervention by King et al. 2015.

• Hypothesis 3: The effect of group cognitive training on gait will be larger as compared to individual dose-matched, computer-based cognitive training performed at home. However, it remains to be determined whether the effect size difference between the two groups will outweigh the advantages of tele-rehabilitation.

• Design: Randomised-controlled trial

• Interventions: experimental group: group cognitive training focusing on executive function and attention; control group: computer-based cognitive training focusing on executive function and attention performed at home. Intervention in both groups will be dose-matched (experimental: 60 mins, 2x/week, 12 weeks; control: 30 mins, 4x/week, 12 weeks)

• Follow-up: at 1 and 3 months time points.

• Power analysis results: at least 38 patients.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 50
• Est. completion date: December 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

• diagnosis of Parkinson´s disease (PD)

• PD duration =8 years

• mild cognitive impairment

• stable medication

• presence of freezing of gait according to the FoG-Q AND/OR Rapid Turns Test

Exclusion Criteria:

• dementia

• deep brain stimulation, pump therapy with Duodopa or Apomorphine

• severe fluctuations with ON state duration for less than 2 hours

• dopa dysregulation syndrome

• impulse control disorder

• untreated depression

• benzodiazepines except for single dose at night

• non-compliance

• inability to walk without support

• significant co-morbidities likely to affect gait, e.g., acute illness, orthopedic disease, significant visual problems, or a clinical history of stroke

• involvement in other treatment trials

• not meeting inclusion criteria

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Behavioral:
• cognitive training
Cognitive training focused on executive function, attention and working memory delivered either by the therapist in a group setting (experimental group) or by a specialized software for cognitive training (Rehacom) at home.

Locations

Country	Name	City	State
Czechia	General University Hospital in Prague	Prague

Sponsors (2)

Lead Sponsor	Collaborator
General University Hospital, Prague	Charles University, Czech Republic

Country where clinical trial is conducted

Czechia, 

References & Publications (10)

Amboni M, Barone P, Hausdorff JM. Cognitive contributions to gait and falls: evidence and implications. Mov Disord. 2013 Sep 15;28(11):1520-33. doi: 10.1002/mds.25674. — View Citation

Bertoli M, Croce UD, Cereatti A, Mancini M. Objective measures to investigate turning impairments and freezing of gait in people with Parkinson's disease. Gait Posture. 2019 Oct;74:187-193. doi: 10.1016/j.gaitpost.2019.09.001. Epub 2019 Sep 5. — View Citation

Heremans E, Nieuwboer A, Spildooren J, Vandenbossche J, Deroost N, Soetens E, Kerckhofs E, Vercruysse S. Cognitive aspects of freezing of gait in Parkinson's disease: a challenge for rehabilitation. J Neural Transm (Vienna). 2013 Apr;120(4):543-57. doi: 10.1007/s00702-012-0964-y. Epub 2013 Jan 18. — View Citation

Keus SHJ MM, Graziano M, et al. European Physiotherapy Guideline for Parkinson´s Disease. the Netherlands: KNGF/ParkinsonNet,2014.

King LA, Wilhelm J, Chen Y, Blehm R, Nutt J, Chen Z, Serdar A, Horak FB. Effects of Group, Individual, and Home Exercise in Persons With Parkinson Disease: A Randomized Clinical Trial. J Neurol Phys Ther. 2015 Oct;39(4):204-12. doi: 10.1097/NPT.0000000000000101. — View Citation

Milman U, Atias H, Weiss A, Mirelman A, Hausdorff JM. Can cognitive remediation improve mobility in patients with Parkinson's disease? Findings from a 12 week pilot study. J Parkinsons Dis. 2014;4(1):37-44. doi: 10.3233/JPD-130321. — View Citation

Peterson DS, King LA, Cohen RG, Horak FB. Cognitive Contributions to Freezing of Gait in Parkinson Disease: Implications for Physical Rehabilitation. Phys Ther. 2016 May;96(5):659-70. doi: 10.2522/ptj.20140603. Epub 2015 Sep 17. — View Citation

Schwenk M, Zieschang T, Oster P, Hauer K. Dual-task performances can be improved in patients with dementia: a randomized controlled trial. Neurology. 2010 Jun 15;74(24):1961-8. doi: 10.1212/WNL.0b013e3181e39696. Epub 2010 May 5. — View Citation

Walton CC, Shine JM, Mowszowski L, Naismith SL, Lewis SJ. Freezing of gait in Parkinson's disease: current treatments and the potential role for cognitive training. Restor Neurol Neurosci. 2014;32(3):411-22. doi: 10.3233/RNN-130370. — View Citation

Yogev-Seligmann G, Hausdorff JM, Giladi N. The role of executive function and attention in gait. Mov Disord. 2008 Feb 15;23(3):329-42; quiz 472. doi: 10.1002/mds.21720. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Counting: number of (correct) answers per second	Patient is asked to subtract 3 from a random number between 51-100 while seated. This assessment is used as a reference value for TUG-DT and 10MWT-DT	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	MDS-Unified Parkinson's Disease Rating Scale	Scale evaluating various aspects of Parkinson's disease including non-motor and motor experiences of daily living and motor complications.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Freezing of Gait Questionnaire	Subjective evaluation of freezing of gait	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Quantitative MRI metrics	Volumetric parameters	Baseline
Other	Quantitative MRI metrics	Vascular white matter lesional volume	Baseline
Other	Quantitative MRI metrics	Resting functional connectivity	Baseline
Other	Auditory Verbal Learning Test (AVLT): T1 (Try) T2 T3 T4 T5 T1-5 Total score Interfence, Total score T6, Total score Delayed recall, Total score Recognition, Correct answers total score, False answers total score	Assessing of auditory memory, memory capacity, ability to learn, delayed recall, recognition	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Phonemic Verbal Fluency FAS, letters: K, P, S Letter K, Total score Letter P, Total Score Letter S, Total score Letters K, P, S, Total score	Assessing of executive functions - initation, maintenance, stop and end the activity	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Semantic Fluency, category: Animals, Total score	Assessing of phatic functions.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Trail Making Test B (TMT B): Total score (in seconds), Number of errors	Assessing of executive functions - cognitive flexibility.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Digit Span Forward, Wechsler Adult Intelligence Scale-Revised, Total score Digit Span Forward, Wechsler Adult Intelligence Scale-Revised, Total score	Assessing of focused auditory attention.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Digit Span Backward, Wechsler Adult Intelligence Scale-Revised, Total score	Working memory capacity measurement.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Digit Symbol, Wechsler Adult Intelligence Scale-Revised, Total score	Assessing of divided attention and working memory.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Grooved Pegboard, Left.	Assessing of visual-motor coordination. The Grooved Pegboard is a manipulative dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	The Parkinson´s Disease Questionnaire (PDQ-39)	Self-assessment quality of life scale for patients with Parkinson's disease. Patient fills it at home.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Grooved Pegboard, Right.	Assessing of visual-motor coordination. The Grooved Pegboard is a manipulative dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Other	Exploratory assessment of relationship between clinical effects of cognitive training and blood signature of polymorphisms in PD-related genes	Custom genetic panel (SureSelect, Agilent) for mutational analysis of 177 genes (including APOE, MAPT, GBA LRRK2, etc.)	Baseline
Primary	Change from Baseline instrumental assessment of turn fluency during rapid turns at 12 weeks	see Bertoli et al. 2019 for a detailed description; G-Walk instrumental gait assessment will be used	Baseline and 12 weeks
Primary	Change from Baseline Timed Up and Go Test: dual-task performance at 12 weeks	Patient is asked to perform TUG while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used	Baseline and 12 weeks
Secondary	Timed Up and Go Test: single-task performance	G-Walk instrumental gait assessment will be used	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	10-meter walking test: single-task performance	G-Walk instrumental gait assessment will be used	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	10-meter walking test: dual-task performance	Patient is asked to perform 10MWT while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	Number of steps/day	Assessed using Fitbit activity trackers	5 days monitoring at baseline and 12 weeks
Secondary	The Montreal Cognitive Assessment (MoCA), Total score	Global cognition screening	Baseline, 12 weeks, 3 months follow-up
Secondary	Trail Making Test A (TMT A), Total score (in seconds)	Assessing of attention distribution.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	The Victoria Version of Stroop Test (VST): Dot Time Score (in seconds) Neutral Word Time Score (in seconds) The Victoria Version of Stroop Test (VST): Dot Time Score (in seconds) Neutral Word Time Score (in seconds)	Assessing of focused visual attention	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	The Victoria Version of Stroop Test (VST): Color Word Time Score (in seconds) Error score on VST Color Word Task, Total score	Assessing of executive functions - inhibition	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	Tower of London, Total score	Assessing of executive functions - problem solving	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	Depression, Anxiety and Stress Scale (DASS 21)	Self-assessment scale of depression, anxiety and stress. Patient fills it at home.	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	Falls Efficacy Scale-International	Fear of falls assessment	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	Number of falls	Diary based quantification of the number of falls	Baseline, 12 weeks, 1 month follow-up, 3 months follow-up
Secondary	Change from post-intervention instrumental assessment of turn fluency during rapid turns at 1 month follow-up	see Bertoli et al. 2019 for a detailed description; G-Walk instrumental gait assessment will be used	12 weeks and 1 month follow-up
Secondary	Change from post-intervention instrumental assessment of turn fluency during rapid turns at 3 months follow-up	see Bertoli et al. 2019 for a detailed description; G-Walk instrumental gait assessment will be used	12 weeks and 3 months follow-up
Secondary	Change from post-intervention Timed Up and Go Test: dual-task performance at 1 month follow-up	Patient is asked to perform TUG while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used	12 weeks and 1 month follow-up
Secondary	Change from post-intervention Timed Up and Go Test: dual-task performance at 3 months follow-up	Patient is asked to perform TUG while subtracting 3 from a random number between 51-100; G-Walk instrumental gait assessment will be used	12 weeks and 3 months follow-up