TY - JOUR
T1 - The use of biotelemetry to explore disease progression markers in amyotrophic lateral sclerosis
AU - Kelly, Madeline
AU - Lavrov, Arseniy
AU - Garcia-Gancedo, Luis
AU - Parr, Jim
AU - Hart, Robert
AU - Chiwera, Theresa
AU - Shaw, Christopher E
AU - Al-Chalabi, Ammar
AU - Marsden, Rachael
AU - Turner, Martin R
AU - Talbot, Kevin
PY - 2020
Y1 - 2020
N2 - Objective: To explore novel, real-world biotelemetry disease progression markers in patients with amyotrophic lateral sclerosis (ALS) and to compare with clinical gold-standard measures. Methods: This was an exploratory, non-controlled, non-drug 2-phase study comprising a variable length Pilot Phase (n = 5) and a 48-week Core study Phase (n = 25; NCT02447952). Patients with mild or moderate ALS wore biotelemetry sensors for ∼3 days/month at home, measuring physical activity, heart rate variability (HRV), and speech over 48 weeks. These measures were assessed longitudinally in relation to ALS Functional Rating Scale-Revised (ALSFRS-R) score and forced vital capacity (FVC); assessed by telephone [monthly] and clinic visits [every 12 weeks]). Results: Pilot Phase data supported progression into the Core Phase, where a decline in physical activity from baseline followed ALS progression as measured by ALSFRS-R and FVC. Four endpoints showed moderate or strong between-patient correlations with ALSFRS-R total and gross motor domain scores (defined as a correlation coefficient of ≥0.5 or >0.7, respectively): average daytime active; percentage of daytime active; total daytime activity score; total 24-hour activity score. Moderate correlations were observed between speech endpoints and ALSFRS-R bulbar domain scores; HRV data quality was insufficient for reliable assessment. The sensor was generally well tolerated; 6/25 patients reported mostly mild or moderate intensity skin and subcutaneous tissue disorder adverse events. Conclusions: Biotelemetry measures of physical activity in this Pilot Study tracked ALS progression over time, highlighting their potential as endpoints for future clinical trials. A larger, formally powered study is required to further support activity endpoints as novel disease progression markers.
AB - Objective: To explore novel, real-world biotelemetry disease progression markers in patients with amyotrophic lateral sclerosis (ALS) and to compare with clinical gold-standard measures. Methods: This was an exploratory, non-controlled, non-drug 2-phase study comprising a variable length Pilot Phase (n = 5) and a 48-week Core study Phase (n = 25; NCT02447952). Patients with mild or moderate ALS wore biotelemetry sensors for ∼3 days/month at home, measuring physical activity, heart rate variability (HRV), and speech over 48 weeks. These measures were assessed longitudinally in relation to ALS Functional Rating Scale-Revised (ALSFRS-R) score and forced vital capacity (FVC); assessed by telephone [monthly] and clinic visits [every 12 weeks]). Results: Pilot Phase data supported progression into the Core Phase, where a decline in physical activity from baseline followed ALS progression as measured by ALSFRS-R and FVC. Four endpoints showed moderate or strong between-patient correlations with ALSFRS-R total and gross motor domain scores (defined as a correlation coefficient of ≥0.5 or >0.7, respectively): average daytime active; percentage of daytime active; total daytime activity score; total 24-hour activity score. Moderate correlations were observed between speech endpoints and ALSFRS-R bulbar domain scores; HRV data quality was insufficient for reliable assessment. The sensor was generally well tolerated; 6/25 patients reported mostly mild or moderate intensity skin and subcutaneous tissue disorder adverse events. Conclusions: Biotelemetry measures of physical activity in this Pilot Study tracked ALS progression over time, highlighting their potential as endpoints for future clinical trials. A larger, formally powered study is required to further support activity endpoints as novel disease progression markers.
KW - Clinical trials
KW - biomarker
KW - epidemiology
UR - http://www.scopus.com/inward/record.url?scp=85087341059&partnerID=8YFLogxK
U2 - 10.1080/21678421.2020.1773501
DO - 10.1080/21678421.2020.1773501
M3 - Article
C2 - 32573278
SN - 2167-8421
VL - 21
SP - 563
EP - 573
JO - Amyotrophic lateral sclerosis & frontotemporal degeneration
JF - Amyotrophic lateral sclerosis & frontotemporal degeneration
IS - 7-8
ER -