Provocation of Freezing of Gait in Parkinson's Disease

NCT04799613 | Completed DMC

• 1 other identifier: 19-6049-B
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Sample Size N= 10 Parkinson's disease patients with self-reported freezing of gait and 10 without self-reported freezing of gait (in total, 20 Parkinson's disease patients) Accrual Period Single visit for 2 hours Study Design This is a cross-sectional study with an intervention to provoke freezing of gait using split-belt treadmill in Parkinson's disease patients with a randomized cross-over design. After baseline evaluation (a), interventions to induce freezing of gait will be performed in a randomized order to avoid a practice/fatigue effect in the following conditions using combination of 4 interventions: walking speed (fast walking vs. natural walking), visual loading (passing through narrow pathway), cognitive loading (dual task), and asymmetry (best side reduction).

• Conditions b-h will be carried out on a split-belt treadmill (Grail systems®, by Motek, Netherlands).
• (b-i) freezing of gait episodes will be identified with synchronized videorecordings (screening done by two independent observers). Episodes identified by both observers will be confirmed and measured by comparing the relative height of metatarsal and heel markers of each foot, in keeping with a previous study evaluating freezing of gait episode on a treadmill. Study Duration
• (Baselines evaluation) Enrolment and assessment (Montreal cognitive assessment, Movement Disorders Society-unified Parkinson's disease rating scale part 2, 3 and 4, Activities-Specific Balance Confidence Scale, Parkinson's disease questionnaire-39, and New freezing of gait questionnaire)
• (a) Formal gait analysis using split-belt treadmill (Grail systems®, by Motek, Netherlands) will be done for baseline assessment (normal walking) and to test patient's ability for fast walking (25% of the normal speed).
• (b-h) Provocation of freezing of gait at split-belt treadmill (Grail systems®, by Motek, Netherlands) with natural and fast walking with/without additional loading or interventions on the asymmetry
• Fast walking will be defined as walking 25% faster than the normal comfortable walking. Subjects who cannot reach this speed, will be asked to walk at their safest maximum speed.
• Passing narrow pathway will be done by walking in a "rope bridge" scene in virtual reality (VR).
• Dual cognitive task will be carried out with serial subtraction prompted on the screen in VR.
• Best side reduction will be defined as 25% slower speed on the best side based on the speed during the initial natural walking with tied configuration setting based on a previous study.3
• Condition b-h will be randomized.

Conditions

Parkinson Disease; Freezing of Gait

Keywords

Parkinson; freezing; spilt-belt; Dual task; visual

Outcome Measures

Primary Outcomes (1)

• number of freezing of gait

  provoked freezing of gait during each situation

  Within intervention (2mins for each situation)

Secondary Outcomes (2)

• Correlation with Montreal cognitive assessment, Movement Disorders Society-unified Parkinson's disease rating scale part 2 and 3, Activities-Specific Balance Confidence Scale, Parkinson's disease questionnaire-39, and New freezing of gait questionnaire

  Within intervention (2mins for each situation)

• Comparison of number/duration of provoked freezing of gait among the situations between Parkinson's disease patients with and without freezing of gait

  Within intervention (2mins for each situation)

Study Arms (16)

Natural walking

NO INTERVENTION

fast walking

EXPERIMENTAL

Other: walking speed

normal walking passing through narrow pathway

EXPERIMENTAL

Other: visual loading

fast walking passing through narrow pathway

EXPERIMENTAL

Other: walking speed; Other: visual loading

Natural walking with dual task

EXPERIMENTAL

Other: dual task

fast walking with dual task

EXPERIMENTAL

Other: walking speed; Other: dual task

Natural walking passing through narrow pathway and during cognitive dual task

EXPERIMENTAL

Other: visual loading; Other: dual task

fast walking passing through narrow pathway and during cognitive dual task

EXPERIMENTAL

Other: walking speed; Other: visual loading; Other: dual task

Natural walking reducing the best side

EXPERIMENTAL

Other: best side reduction

fast walking reducing the best side

EXPERIMENTAL

Other: walking speed; Other: best side reduction

Natural walking reducing the best side passing through narrow pathway

EXPERIMENTAL

Other: visual loading; Other: best side reduction

fast walking reducing the best side passing through narrow pathway

EXPERIMENTAL

Other: walking speed; Other: visual loading; Other: best side reduction

Natural walking reducing the best side with cognitive dual task

EXPERIMENTAL

Other: dual task; Other: best side reduction

fast walking reducing the best side with cognitive dual task

EXPERIMENTAL

Other: walking speed; Other: dual task; Other: best side reduction

Natural walking reducing the best side passing through narrow pathway and during cognitive dual task

EXPERIMENTAL

Other: visual loading; Other: dual task; Other: best side reduction

fast walking reducing the best side passing through narrow pathway and during cognitive dual task

EXPERIMENTAL

Other: walking speed; Other: visual loading; Other: dual task; Other: best side reduction

Interventions

walking speed OTHER

walking speed (normal speed vs. fast speed). fast speed was 25% faster than normal speed

fast walking; fast walking passing through narrow pathway; fast walking passing through narrow pathway and during cognitive dual task; fast walking reducing the best side; fast walking reducing the best side passing through narrow pathway; fast walking reducing the best side passing through narrow pathway and during cognitive dual task; fast walking reducing the best side with cognitive dual task; fast walking with dual task

visual loading OTHER

visual loading (walking through narrow pathway using VR)

Natural walking passing through narrow pathway and during cognitive dual task; Natural walking reducing the best side passing through narrow pathway; Natural walking reducing the best side passing through narrow pathway and during cognitive dual task; fast walking passing through narrow pathway; fast walking passing through narrow pathway and during cognitive dual task; fast walking reducing the best side passing through narrow pathway; fast walking reducing the best side passing through narrow pathway and during cognitive dual task; normal walking passing through narrow pathway

dual task OTHER

dual task (serial subtraction using VR)

Natural walking passing through narrow pathway and during cognitive dual task; Natural walking reducing the best side passing through narrow pathway and during cognitive dual task; Natural walking reducing the best side with cognitive dual task; Natural walking with dual task; fast walking passing through narrow pathway and during cognitive dual task; fast walking reducing the best side passing through narrow pathway and during cognitive dual task; fast walking reducing the best side with cognitive dual task; fast walking with dual task

best side reduction OTHER

best side reduction (split belt mode, the speed of best side was reduced by 25% compared to the other side)

Natural walking reducing the best side; Natural walking reducing the best side passing through narrow pathway; Natural walking reducing the best side passing through narrow pathway and during cognitive dual task; Natural walking reducing the best side with cognitive dual task; fast walking reducing the best side; fast walking reducing the best side passing through narrow pathway; fast walking reducing the best side passing through narrow pathway and during cognitive dual task; fast walking reducing the best side with cognitive dual task

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Idiopathic Parkinson's disease
• Hoehn \& Yahr Stage 1-3
• Ten with self-reported freezing of gait (score of 1 in part 1 of new freezing of gait questionnaire), and 10 without FOG..
• Sequence effect on feet (as score of at least 2 in the leg agility (item#3.8) of Movement Disorders Society-Unified Parkinson's disease rating scale part 3)
• Stable clinical response to medications or stimulation parameters for at least 1 months
• Able to walk on a motor-driven treadmill
• Ability to provide informed consent

You may not qualify if:

• Severe imbalance that limits ambulation (Hoehn \&Yahr score above 4)
• Orthostatic hypotension
• Orthopedic conditions and other systemic disease affecting locomotion
• Shortness of breath and cardiac disease
• Psychiatric disorders needing medication
• Dementia
• Presence of other neurological disorder

Sponsors & Collaborators

• University of Toronto: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (32)

• Nieuwboer A, Rochester L, Herman T, Vandenberghe W, Emil GE, Thomaes T, Giladi N. Reliability of the new freezing of gait questionnaire: agreement between patients with Parkinson's disease and their carers. Gait Posture. 2009 Nov;30(4):459-63. doi: 10.1016/j.gaitpost.2009.07.108. Epub 2009 Aug 5.

  PMID: 19660949 BACKGROUND

• Fasano A, Herzog J, Seifert E, Stolze H, Falk D, Reese R, Volkmann J, Deuschl G. Modulation of gait coordination by subthalamic stimulation improves freezing of gait. Mov Disord. 2011 Apr;26(5):844-51. doi: 10.1002/mds.23583. Epub 2011 Mar 2.

  PMID: 21370271 BACKGROUND

• Fasano A, Schlenstedt C, Herzog J, Plotnik M, Rose FEM, Volkmann J, Deuschl G. Split-belt locomotion in Parkinson's disease links asymmetry, dyscoordination and sequence effect. Gait Posture. 2016 Jul;48:6-12. doi: 10.1016/j.gaitpost.2016.04.020. Epub 2016 Apr 27.

  PMID: 27477701 BACKGROUND

• Giladi N, Kao R, Fahn S. Freezing phenomenon in patients with parkinsonian syndromes. Mov Disord. 1997 May;12(3):302-5. doi: 10.1002/mds.870120307.

  PMID: 9159723 BACKGROUND

• Giladi N, Treves TA, Simon ES, Shabtai H, Orlov Y, Kandinov B, Paleacu D, Korczyn AD. Freezing of gait in patients with advanced Parkinson's disease. J Neural Transm (Vienna). 2001;108(1):53-61. doi: 10.1007/s007020170096.

  PMID: 11261746 BACKGROUND

• Chee R, Murphy A, Danoudis M, Georgiou-Karistianis N, Iansek R. Gait freezing in Parkinson's disease and the stride length sequence effect interaction. Brain. 2009 Aug;132(Pt 8):2151-60. doi: 10.1093/brain/awp053. Epub 2009 May 11.

  PMID: 19433440 BACKGROUND

• Plotnik M, Giladi N, Balash Y, Peretz C, Hausdorff JM. Is freezing of gait in Parkinson's disease related to asymmetric motor function? Ann Neurol. 2005 May;57(5):656-63. doi: 10.1002/ana.20452.

  PMID: 15852404 BACKGROUND

• Youn J, Okuma Y, Hwang M, Kim D, Cho JW. Falling Direction can Predict the Mechanism of Recurrent Falls in Advanced Parkinson's Disease. Sci Rep. 2017 Jun 20;7(1):3921. doi: 10.1038/s41598-017-04302-7.

  PMID: 28634343 BACKGROUND

• Giladi N. Medical treatment of freezing of gait. Mov Disord. 2008;23 Suppl 2:S482-8. doi: 10.1002/mds.21914.

  PMID: 18668620 BACKGROUND

• Sawada M, Wada-Isoe K, Hanajima R, Nakashima K. Clinical features of freezing of gait in Parkinson's disease patients. Brain Behav. 2019 Apr;9(4):e01244. doi: 10.1002/brb3.1244. Epub 2019 Mar 9.

  PMID: 30851088 BACKGROUND

• Snijders AH, Weerdesteyn V, Hagen YJ, Duysens J, Giladi N, Bloem BR. Obstacle avoidance to elicit freezing of gait during treadmill walking. Mov Disord. 2010 Jan 15;25(1):57-63. doi: 10.1002/mds.22894.

  PMID: 19938174 BACKGROUND

• Spildooren J, Vercruysse S, Desloovere K, Vandenberghe W, Kerckhofs E, Nieuwboer A. Freezing of gait in Parkinson's disease: the impact of dual-tasking and turning. Mov Disord. 2010 Nov 15;25(15):2563-70. doi: 10.1002/mds.23327.

  PMID: 20632376 BACKGROUND

• Ginis P, Nackaerts E, Nieuwboer A, Heremans E. Cueing for people with Parkinson's disease with freezing of gait: A narrative review of the state-of-the-art and novel perspectives. Ann Phys Rehabil Med. 2018 Nov;61(6):407-413. doi: 10.1016/j.rehab.2017.08.002. Epub 2017 Sep 7.

  PMID: 28890341 BACKGROUND

• Lu C, Amundsen Huffmaster SL, Tuite PJ, Vachon JM, MacKinnon CD. Effect of Cue Timing and Modality on Gait Initiation in Parkinson Disease With Freezing of Gait. Arch Phys Med Rehabil. 2017 Jul;98(7):1291-1299.e1. doi: 10.1016/j.apmr.2017.01.009. Epub 2017 Feb 4.

  PMID: 28167093 BACKGROUND

• Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011 Aug;10(8):734-44. doi: 10.1016/S1474-4422(11)70143-0.

  PMID: 21777828 BACKGROUND

• Nonnekes J, Bloem BR. Biphasic Levodopa-Induced Freezing of Gait in Parkinson's Disease. J Parkinsons Dis. 2020;10(3):1245-1248. doi: 10.3233/JPD-201997.

  PMID: 32417798 BACKGROUND

• Barbe MT, Amarell M, Snijders AH, Florin E, Quatuor EL, Schonau E, Fink GR, Bloem BR, Timmermann L. Gait and upper limb variability in Parkinson's disease patients with and without freezing of gait. J Neurol. 2014 Feb;261(2):330-42. doi: 10.1007/s00415-013-7199-1. Epub 2013 Dec 4.

  PMID: 24305993 BACKGROUND

• Hausdorff JM, Schaafsma JD, Balash Y, Bartels AL, Gurevich T, Giladi N. Impaired regulation of stride variability in Parkinson's disease subjects with freezing of gait. Exp Brain Res. 2003 Mar;149(2):187-94. doi: 10.1007/s00221-002-1354-8. Epub 2003 Jan 22.

  PMID: 12610686 BACKGROUND

• Nanhoe-Mahabier W, Snijders AH, Delval A, Weerdesteyn V, Duysens J, Overeem S, Bloem BR. Split-belt locomotion in Parkinson's disease with and without freezing of gait. Neuroscience. 2013 Apr 16;236:110-6. doi: 10.1016/j.neuroscience.2013.01.038. Epub 2013 Jan 29.

  PMID: 23370318 BACKGROUND

• Ricciardi L, Ricciardi D, Lena F, Plotnik M, Petracca M, Barricella S, Bentivoglio AR, Modugno N, Bernabei R, Fasano A. Working on asymmetry in Parkinson's disease: randomized, controlled pilot study. Neurol Sci. 2015 Aug;36(8):1337-43. doi: 10.1007/s10072-015-2082-8. Epub 2015 Feb 13.

  PMID: 25677846 BACKGROUND

• Seuthe J, D'Cruz N, Ginis P, Becktepe JS, Weisser B, Nieuwboer A, Schlenstedt C. The Effect of One Session Split-Belt Treadmill Training on Gait Adaptation in People With Parkinson's Disease and Freezing of Gait. Neurorehabil Neural Repair. 2020 Oct;34(10):954-963. doi: 10.1177/1545968320953144. Epub 2020 Sep 17.

  PMID: 32940131 BACKGROUND

• D'Cruz N, Seuthe J, Ginis P, Hulzinga F, Schlenstedt C, Nieuwboer A. Short-Term Effects of Single-Session Split-Belt Treadmill Training on Dual-Task Performance in Parkinson's Disease and Healthy Elderly. Front Neurol. 2020 Sep 30;11:560084. doi: 10.3389/fneur.2020.560084. eCollection 2020.

  PMID: 33101174 BACKGROUND

• Berardelli A, Rothwell JC, Thompson PD, Hallett M. Pathophysiology of bradykinesia in Parkinson's disease. Brain. 2001 Nov;124(Pt 11):2131-46. doi: 10.1093/brain/124.11.2131.

  PMID: 11673316 BACKGROUND

• Bologna M, Guerra A, Paparella G, Giordo L, Alunni Fegatelli D, Vestri AR, Rothwell JC, Berardelli A. Neurophysiological correlates of bradykinesia in Parkinson's disease. Brain. 2018 Aug 1;141(8):2432-2444. doi: 10.1093/brain/awy155.

  PMID: 29901693 BACKGROUND

• Iansek R, Huxham F, McGinley J. The sequence effect and gait festination in Parkinson disease: contributors to freezing of gait? Mov Disord. 2006 Sep;21(9):1419-24. doi: 10.1002/mds.20998.

  PMID: 16773644 BACKGROUND

• Peterson DS, Fling BW, Mancini M, Cohen RG, Nutt JG, Horak FB. Dual-task interference and brain structural connectivity in people with Parkinson's disease who freeze. J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):786-92. doi: 10.1136/jnnp-2014-308840. Epub 2014 Sep 15.

  PMID: 25224677 BACKGROUND

• Plotnik M, Giladi N, Hausdorff JM. Is freezing of gait in Parkinson's disease a result of multiple gait impairments? Implications for treatment. Parkinsons Dis. 2012;2012:459321. doi: 10.1155/2012/459321. Epub 2012 Jan 12.

  PMID: 22288021 BACKGROUND

• Nonnekes J, Janssen AM, Mensink SH, Oude Nijhuis LB, Bloem BR, Snijders AH. Short rapid steps to provoke freezing of gait in Parkinson's disease. J Neurol. 2014 Sep;261(9):1763-7. doi: 10.1007/s00415-014-7422-8. Epub 2014 Jun 24.

  PMID: 24957299 BACKGROUND

• Morris M, Iansek R, Matyas T, Summers J. Abnormalities in the stride length-cadence relation in parkinsonian gait. Mov Disord. 1998 Jan;13(1):61-9. doi: 10.1002/mds.870130115.

  PMID: 9452328 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

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Peto V, Jenkinson C, Fitzpatrick R, Greenhall R. The development and validation of a short measure of functioning and well being for individuals with Parkinson's disease. Qual Life Res. 1995 Jun;4(3):241-8. doi: 10.1007/BF02260863.

  PMID: 7613534 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Walking Speed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Gait; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Walking; Locomotion; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 16, 2021
• Study Start: March 15, 2021
• Primary Completion: June 15, 2022
• Study Completion: June 15, 2022
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)