Improving Gait Adaptability in Hereditary Spastic Paraplegia
Condition: Hereditary Spastic Paraplegia; Strumpell Disease
MeSH terms: Muscle Spasticity; Paraplegia; Spastic Paraplegia, Hereditary
Study type: Interventional

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.
    

Intervention name(s): C-mill intervention; No intervention
Intervention type(s): Behavioral; Other
Intervention description(s): A five week personalised rehabilitation program. 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. The treatment is implemented in a five week period via 10 biweekly sessions. Each treatment session lasts 60 minutes. In total, participants will receive C-mill training for a total of ten hours. The training will be carried out by a skilled physiotherapist.; Participants in the control group are placed on a waiting list.
Allocation: Randomized
Intervention model: Crossover Assignment
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.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: hereditary spastic paraplegia; C-mill; gait adaptability; rehabilitation