Timed walk as primary outcome measure of treatment response in clinical trials for HTLV-1-associated myelopathy: a feasibility study

Abstract

BackgroundTo advance the treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), randomised controlled therapeutic studies with appropriate and sensitive outcomes are reuired. One candidate outcome is the 10-metre walk test (10MWT), a patient-centred, simple and functional measure. To calculate sample size based on 10MWT as the primary outcome, variability within and between subjects must be known.MethodsData on 10MWT from 76 patients with HAM/TSP were prospectively collected from four specialist centres in Brazil, Japan, USA and UK. Data, collected at two time points, 6 months apart, were log transformed and subjected to analysis of covariance.ResultsBaseline mean (standard deviation = SD), median 10MWT were 23.5 (18.9), 16.3 s/10 m and at 6 months 24.9 (23.9), 16.4 s/10 m. The mean (SD) % increase in walk time was 5.74 % (28.2 %). After logarithmic transformation, the linear correlation between baseline and 24 weeks 10MWT was r = 0.938. Using these data, it was determined that a randomised controlled trial with 30 participants per group would have 90 % power to detect a 19 % decrease or a 23 % increase in 10MWT.ConclusionsThe intra-patient variability of 10MWT is relatively small in HAM/TSP over 6 months. 10MWT is a feasible outcome measure for a clinical trial in HAM/TSP. To our knowledge, this is the first ever recommendation for the sample size required for trials in HAM/TSP patients.

Balance, functional mobility, and fall occurrence in patients with human T-cell lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis: a cross-sectional study

“…In the present study, it was observed that patients with HAM/ TSP were female, older than 40 years, and with necessity of some aid for locomotion. These findings are consistent with the sociodemographic and clinical profile found in previous studies 5,7,8,12 . Some authors suggest that many patients with symptomatic HAM/TSP may even require wheelchairs 12,14 .…”

“…Human T-cell lymphotropic virus type-1 (HTLV-1)associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disorder caused by demyelination and axonal destruction of the spinal cord [1][2][3] . This health condition is more prevalent in women older than 40 years of age [2][3][4][5][6][7][8] . Patients with HAM/TSP have motor, sensory, and autonomic alterations, which may influence gait performance, balance maintenance, and functional mobility [2][3][4] .…”

Efficacy of Corticosteroid Therapy for HTLV-1-Associated Myelopathy: A Randomized Controlled Trial (HAMLET-P)

“…Therefore, 10 mWT is a simple and reliable outcome measure for HAM with a minimal burden on patients. Next, the 10 mWT of the placebo group improved, which was contrary to the results of clinical observations [28]. Thus, the placebo effect is nonnegligible in clinical trials on HAM.…”

“…In slow progressors, we used 10 mWT as the primary outcome because it is a sensitive and objective functional measure with small intra-patient variability, and it can worsen by an average of 5.74% per 6 months in untreated patients with HAM [28]. Based on our clinical experience, there was an improvement of approximately 15% per 6 months with prednisolone (unpublished data), which is roughly equivalent to 2 years worth of gait deterioration.…”

Research scenario in physiotherapy for people with human t-cell lymphotropic virus (HTLV): scientometric study / Cenário das pesquisas em Fisioterapia para pessoas com Human T-Cell Lymphotropic Virus (HTLV): estudo cientométrico

“…Based on the observational studies, it is confirmed that the main problems that affect these patients involve disorders of gait 21,22,8,23 , balance 24,25,26 , pelvic floor 27,28 spasticity 29,30 and pain 10,31,32,33 . These dysfunctions affect daily life activities 5,34 and quality of life 35 .…”