Clinical trial NCT04180098: Improving Gait Adaptability in Hereditary Spastic Paraplegia
Official title: Improving Gait Adaptability in Hereditary Spastic Paraplegia During Task-specific Training on the C-Mill: Towards Evidence-Based and Individually Tailored Rehabilitation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Spastic Paraplegia
Strumpell Disease
Keywords: hereditary spastic paraplegia
C-mill
gait adaptability
rehabilitation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Jacques and Gloria Gossweiler Foundation
First posted: 2019-11-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: All participants monitor their physical activity for 1 week, and falls for 15 weeks. After the screening, participants are randomized. Gait and balance capacity will be assessed in the movement lab of Radboudumc. Participants in the intervention group receives 5 weeks of C-mill training, which is immediately followed by an assessment in the movement lab, one-week of activity monitoring and fall monitoring during a 15 week follow-up period. After follow-up they will receive a final assessment in our movement lab. Participants in the control (waiting list) intervention, continue usual care for 5 weeks, followed by an assessment in the movement lab and one-week of activity monitoring. Subsequently, they receive 5 weeks of C-mill training, followed by an assessment in the movement lab, one-week of activity monitoring and fall monitoring in a follow-up period of 15 weeks. After follow-up, they receive a final assessment in the movement lab.
Primary purpose: BASIC_SCIENCE

Brief summary: This study evaluates the effects of ten hours C-mill training on gait adaptability in participants with hereditary spastic paraplegia (HSP). Half of the participants start with five weeks of C-mill training (ten 1-hour sessions). The other participants are placed on a waiting list, which is followed by the same five weeks of C-mill training (ten 1-hour sessions). It is hypothesized that ten hours of context specific C-mill training is effective in improving gait adaptability in participants with pure HSP.

Detailed description: Hereditary spastic paraplegia (HSP) is a relatively common, slowly progressive movement disorder that seriously impacts on gait capacity. Patients with HSP experience incremental muscle stiffness, muscle weakness and balance problems and, as a consequence, increasing difficulties to adjust their gait pattern to changing environmental demands. This is a major problem as such 'gait adaptability' is critical for independent and safe mobility in daily life. Impaired gait adaptability will also result in falls and fall-related injuries and reduce quality of life. Therefore, there is an urgent need for evidence-based rehabilitation interventions to improve gait adaptability in patients with HSP. Participants train gait adaptability via obstacle negotiation, precision stepping and unexpected accelerations and decelerations. The strategies are trained in a safe environment on the C-Mill, a treadmill providing augmented reality via visual and acoustic cues.

Objectives

This study aims to promote an essential step towards evidence-based and individually tailored gait rehabilitation in participants with hereditary spastic paraparesis. The objectives are twofold:

1. To study the effect of ten 1-hour sessions C-Mill training on gait adaptability in participants with pure-HSP.
2. To study the effect of ten 1-hour sessions C-Mill training on spatiotemporal and functional capacity parameters and to identify key-determinants of C-Mill training efficacy in participants with pure-HSP.

It is hypothesized that ten hours of context specific C-mill training is effective in improving gait adaptability in participants with pure HSP, as measured with the obstacle subtask of the emory functional ambulation profile (E-FAP).

Sample size calculation is based on previous studies concerning the effects of gait adaptability interventions on the obstacle subtask of the E-FAP. A total of 32 participants is sufficient to demonstrate an expected improvement on the obstacle subtask score of the E-FAP. To allow a 10% attrition rate, 36 participants will be included.

Participants will be recruited from the Radboud Expert Centre of Genetic Movement Disorders (part of the ERN-RND) which has specific HSP expertise. The treating physician of the patient will ask whether the investigator may contact the patient. Furthermore, mailings through the HSP patient group, that is part of the patient organization "Spierziekten Nederland", will be sent to their members with HSP. If patients are interested in participating, they can contact the investigator and will be informed via an information letter (to which the informed consent form is attached). Participants will then have two weeks to consider their decision whether to participate. After the two week period, the investigator will contact them about their decision.

Data will be coded numerically (e.g. HSP01, HSP02) and an identification code list will be used to link the data to the participant. The key to the code will be safeguarded by the investigators. The project leader and all other investigators will have access to the source data. Data will be kept for fifteen years. The handling of data will comply with the Dutch Personal Data Protection Act and participants' privacy will be protected. The monitoring will be performed according to NFU guidelines for negligible risk intensity.

Descriptive data analysis will be used to outline characteristics of both intervention groups. The effect of gait adaptability training on primary and secondary outcomes will be tested using ANCOVA. Post-intervention measurements will be used as dependent variables and Group (C-Mill versus waiting list) and pre-intervention measurements as independent between-subjects factors. Time will be tested as a within-subjects factor. The retention of gait adaptability training will be tested by merging both groups and using a repeated measures ANOVA with Time as a within-subjects factor (C-Mill group: measurements 1, 2 and 3; waiting list: measurements 2, 3 and 4). Post-hoc tests will be performed in the case of significant main or interaction effects, using paired t-tests. Fall rates will be processed descriptively. Depending on the distribution of the data, the rate of near falls may be analyzed using Wilcoxon signed rank test. In addition, to determine key determinants of C-Mill training efficacy, a stepwise linear regression analysis will be performed with training-induced change in gait adaptability (relative change of the obstacle subtask of the E-FAP) as the dependent variable. Univariate analyses will be performed to select the best factors from the available demographic and clinical characteristics.

Adverse events All adverse events reported spontaneously by the participants or observed by the investigator or his staff will be recorded. The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited METC that approved the protocol, within seven days of first knowledge for SAEs that result in death or are life threatening followed by a period of maximum of 8 days to complete the initial preliminary report. All other SAEs will be reported within a period of maximum 15 days after the sponsor has first knowledge of the serious adverse events. The risk associated with participation will be negligible, according to the risk classification of the NFU. Burden associated with the measurements will be limited, as the number of measurements will be relatively low.

Eligibility criteria: Inclusion criteria:

* Diagnosis of pure-HSP based on molecular diagnosis or based on inheritance pattern
* Aged between 18-70 years old
* Being able to walk barefoot on a level ground for 50 meters without a walking aid (use of orthopaedic devices or made-to-measure footwear is allowed).

Exclusion criteria:

* Other neurological or serious orthopaedic or psychiatric co-morbidity
* Previous HSP-related surgical interventions of the lower extremities.

Primary outcomes:
measure: The mean changes in time scores of the obstacle subtask of the emory functional ambulation profile
timeFrame: Pre-intervention (week 0) till post-intervention (week 6)
Secondary outcomes:
measure: The mean change in the time score on the ten meter walk test
timeFrame: Pre-intervention (week 0) till post-intervention (week 6)
measure: The mean change of the mini balance evaluation system
timeFrame: Pre-intervention (week 0) till post-intervention (week 6)
measure: Mean changes of activity levels measured as time spent active of passive during 24 hours
timeFrame: Pre-intervention (week 0) till post-intervention (week 6)
measure: The mean changes in scores of the activities specific balance confidence scale
timeFrame: Pre-intervention (week 0) till post-intervention (week 6)
measure: Mean changes in number of falls and near falls
timeFrame: Pre-intervention (week 0) and after the follow-up period of fifteen weeks (experimental group week 21, control group week 27)
measure: The mean change in the time score on the walking adaptability ladder test
timeFrame: Pre-intervention (week 0) till post-intervention (week 6)
measure: Mean changes in spatio-temporal gait parameters
timeFrame: Pre-intervention (week 0) till post-intervention (week 6)
Other outcomes:
measure: The mean changes in time scores of the obstacle subtask of the emory functional ambulation profile
timeFrame: Pre C-mill intervention (experimental group week 0, control group week 6), post C-Mill intervention (experimental group week 6, control group week 12) and after the follow-up period of fifteen weeks (experimental group week 21, control group week 27)
measure: The mean change in the time score on the ten meter walk test
timeFrame: Pre C-mill intervention (experimental group week 0, control group week 6), post C-Mill intervention (experimental group week 6, control group week 12) and after the follow-up period of fifteen weeks (experimental group week 21, control group week 27)
measure: The mean change of the mini balance evaluation system
timeFrame: Pre C-mill intervention (experimental group week 0, control group week 6), post C-Mill intervention (experimental group week 6, control group week 12) and after the follow-up period of fifteen weeks (experimental group week 21, control group week 27)
measure: Mean changes of activity levels measured as time spent active of passive during 24 hours
timeFrame: Pre C-mill intervention (experimental group week 0, control group week 6) and post C-Mill intervention (experimental group week 6, control group week 12)
measure: The mean changes in scores of the activities specific balance confidence scale
timeFrame: Pre C-mill intervention (experimental group week 0, control group week 6), post C-Mill intervention (experimental group week 6, control group week 12) and after the follow-up period of fifteen weeks (experimental group week 21, control group week 27)
measure: The mean change in the time score on the walking adaptability ladder test
timeFrame: Pre C-mill intervention (experimental group week 0, control group week 6), post C-Mill intervention (experimental group week 6, control group week 12) and after the follow-up period of fifteen weeks (experimental group week 21, control group week 27)
measure: Mean changes in spatio-temporal gait parameters
timeFrame: Pre C-mill intervention (experimental group week 0, control group week 6), post C-Mill intervention (experimental group week 6, control group week 12) and after the follow-up period of fifteen weeks (experimental group week 21, control group week 27)
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud universitair medisch centrum
Study officials:
affiliation: Radboud University Medical Center
name: A.C.H. Geurts, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nonnekes J, van Lith B, van de Warrenburg BP, Weerdesteyn V, Geurts ACH. Pathophysiology, diagnostic work-up and management of balance impairments and falls in patients with hereditary spastic paraplegia. J Rehabil Med. 2017 May 16;49(5):369-377. doi: 10.2340/16501977-2227.
citation: Heeren A, van Ooijen M, Geurts AC, Day BL, Janssen TW, Beek PJ, Roerdink M, Weerdesteyn V. Step by step: a proof of concept study of C-Mill gait adaptability training in the chronic phase after stroke. J Rehabil Med. 2013 Jul;45(7):616-22. doi: 10.2340/16501977-1180.
citation: Fonteyn EM, Heeren A, Engels JJ, Boer JJ, van de Warrenburg BP, Weerdesteyn V. Gait adaptability training improves obstacle avoidance and dynamic stability in patients with cerebellar degeneration. Gait Posture. 2014;40(1):247-51. doi: 10.1016/j.gaitpost.2014.04.190. Epub 2014 Apr 24.
citation: Salinas S, Proukakis C, Crosby A, Warner TT. Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. 2008 Dec;7(12):1127-38. doi: 10.1016/S1474-4422(08)70258-8.
citation: van de Venis L, van de Warrenburg BPC, Weerdesteyn V, van Lith BJH, Geurts ACH, Nonnekes J. Improving gait adaptability in patients with hereditary spastic paraplegia (Move-HSP): study protocol for a randomized controlled trial. Trials. 2021 Jan 7;22(1):32. doi: 10.1186/s13063-020-04932-9.