Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04993274 |
| Other study ID # |
EA1/240/18 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 20, 2019 |
| Est. completion date |
November 2022 |
Study information
| Verified date |
August 2021 |
| Source |
Charite University, Berlin, Germany |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The study explores the application of marker-less motion analysis (visual-perceptive
computing, VPC) using a consumer grade infrared and video camera (Microsoft Kinect) for
clinical assessment in MS. It includes as the primary outcomes a short assessment battery of
simple motor tasks (PASS-MS) that can be performed in front of the sensor after standard oral
instructions given by the operator. For each task, the sensor data are transformed into a set
of kinematic parameters that may be used as motor outcome reflecting specific neurological
dysfunction. For validation against both clinical and patient-reported outcomes as well as
MRI findings, we here prospectively investigate a large cohort of patients with multiple
sclerosis. This will allow to determine the usefulness of the various kinematic parameters
generated and to define a reduced set of the most meaningful parameters for potential use in
future MS trials. Data on repeatability and benchmarks for clinically relevant change are
essential to interpret test results and, more importantly, changes thereof. Further, this
prospective study will yield estimates of progression rates that are required for planning
future studies using this motion analysis tool and assessment battery as an outcome. The
study is designed to obtain benchmarks for sensitivity and clinical responsiveness. Primary
analysis aims to answer the question: Does the SMSW - Maximum Speed worsen with disease
progression established as confirmed disability progression based on EDSS after 24 months
(defined as 1 step increase in EDSS ≤ 5.5 and 0.5 step in EDSS > 5.5)?
Description:
The study is designed as a prospective observational (non-interventional) single-center study
performed at one center, Charité - Universitätsmedizin Berlin.
This study converges with prospective observational studies performed at our center. These
studies started in 2011 with the objective to define determinants of progression in
neuroimmunological disorders (CIS, MS, NMO).
The variables collected for this study were defined according to the study objective and
comprise different markers of motor/mobility function, cognitive and affective function,
fatigue and health-related quality of life. The primary outcome is a VPC-based assessment of
locomotor function (PASS-MS SMSW-MaxS) as the diagnostic test under study. Secondary outcomes
serve to cross-validate progression rates or as benchmarks of clinical progression to
determine clinical relevance of change. Further, possible effects of cognitive and affective
function on the primary outcome can be explored which is of high relevance for the
interpretation of changes in the population of MS.
All assessments are performed at inclusion and after 12and 24 months.
Primary outcome:
PASS-MS kinematic parameters with Short Maximum Speed Walk - Speed (SMSW-MaxS) as primary
outcome
Secondary outcomes:
- Clinical Examination
- Other kinematic parameters derived from PASS-MS
- Clinical Rating with EDSS and Multiple Sclerosis Functional Composite (MSFC) consisting
of tests of walking capacity (T25FW), hand dexterity (9HPT), cognitive processing speed
(SDMT) and visual acuity (Sloan charts)
- Cognitive testing (BRB-N)
- Patient-reported outcomes on global impression of change, MS-related impairment in
walking (MSWS-12), hand function, occurrence of fatigue (FSMC), depressive symptoms
(BDI-II) and health-related quality of life by MS-specific questionnaire (HAQUAMS)
A change in T25FW speed of at least 20% was found to be clinically meaningful for MS patients
(Hobart 2013). In a previous study the investigators found SMSW average walking speed was
slower in MS patients (1.6 ± 0.3 m/sec) than in HC (1.8 ± 0.4 m/sec) (Behrens 2014).
Therefore, a similar average walking speed was assumed for the population under study at
baseline (1.6 m/sec) and a decrease of 0.3 m/sec (corresponding to approximately 20%) as
clinically meaningful. Moreover, based on previous reports, investigators assume a standard
deviation in the changes of SMSW-MaxS of 0.4 m/sec (Behrens 2014). This results in an
expected effect size of 0.75 for the change in SMSW-MaxS between baseline and 24 months
follow-up in those with clinically confirmed disability progression. A sample size of N=16
patients will have a power of 80% to detect an effect size of 0.75 with a two-sided
significance level of 0.05 and a t-test for dependent samples (nQuery Advisor 7.0).
Sample size estimation considered previous evidence on the proportion of patients who will
show clinically confirmed disability progression throughout the observation period based on
an EDSS change defined as 1 step increase in EDSS ≤ 5.5 and 0.5 step in EDSS > 5.5 within 24
months. Cutter et al. (1999) reported that 10% of their patients showed EDSS confirmed
sustained change within 3 months and 40% showed a change to baseline in 1 year reported in
MSFC, which also incorporates the T25FW. The investigators assume that at least 20 % of
patients showing a confirmed sustained change in EDSS according to above definition within
24months to be a realistic scenario.
When considering an overall dropout rate of 10-20% (lost to follow-up), this would result in
N=16 complete datasets when overall N=100 patients are included.
Patients should not have had an acute relapse up to 3 months before follow-up visit (12 and
24 months). To avoid dropout due to acute relapse the follow-up visit is extended to up to 3
months in case of acute relapse.
