Exploratory Study of Biotelemetry in Amyotrophic Lateral Sclerosis

An Exploratory Study to Investigate the Use of Biotelemetry to Identify Markers of Disease Progression in Subjects With Amyotrophic Lateral Sclerosis

Study 201283 is an exploratory, non-controlled, non-drug study in Amyotrophic Lateral Sclerosis (ALS) subjects. This study is being conducted as the first step for developing new meaningful measure(s) which might prove to be more effective than existing measures for monitoring clinical function and disease course in ALS. The objective of this study is to test novel measures of movement/physical activity, heart rate and speech and explore how they measure disease progression by evaluating their relationship to gold standard measures of function. This study will be conducted in two phases. A variable length Pilot Phase to test biotelemetry instruments and algorithms reliability and ease of use/acceptance. Approximately 5 subjects will have at least 1 clinic visit to perform a series of set reference tasks while wearing the accelerometer and electrode. Subjects will also continuously wear the accelerometer and electrode in their routine home-life setting for approximately 3 days after the clinic visit (i.e., home monitoring). Subjects in the Pilot Phase will continue in the study and participate in the Core Study Phase. A 48 week Core Study Phase will be conducted to evaluate how measures of movement/physical activity, speech and Heart Rate Variability (HRV) relate to ALS disease progression. During this phase, a maximum of 25 subjects will be enrolled. Subjects will attend 5 clinic visits to perform gold standard measures of function and perform a series of set reference tasks while wearing the accelerometer and electrode. In between clinic visits, every month subjects will attach the accelerometer and electrode and wear it for approximately 3 days in their home. A telephone contact with the subject will be made by the site at the end of each 3-day home monitoring period.

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Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Device: Faros Sensor (FS) and LifeInsight Hub; Device: Fast Fix electrode patch; Procedure: Quantitative Measure of Speech (Core Phase Only)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 8AF
    • GSK Investigational Site
  • Oxford, United Kingdom, OX3 9DU
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between 18 and 80 years of age, inclusive, at the time of signing the informed consent.
• Diagnosed with ALS by a neurologist with expertise in ALS. For subjects with bulbar onset there must be objective limb involvement of at least one limb.
• Diagnosed with ALS within 18 months of symptom onset.
• Subjects must be ambulatory (i.e., must not be confined to a wheelchair).
• Male and female subjects.
• Capable of giving signed (or verbal consent or assent where applicable) informed consent as described in Protocol which includes compliance with the requirements and restrictions listed in the consent form and in protocol.
• Capable and willing to comply with the requirements of the protocol (either by themselves or with assistance).

Exclusion Criteria:

• Neurological (other than the subject's ALS) or non-neurological co-morbidities (e.g. joint disease, respiratory disease) which limit mobility.
• Clinically significant cognitive impairment in the opinion of the investigator.
• Regionally restricted forms of ALS, or other atypical variants: Isolated corticobulbar pattern of ALS with normal ambulation; Flail arm syndrome; Primary lateral sclerosis; Signs of chronic partial denervation restricted to a single limb; ALS parkinsonism dementia complex
• Subjects requiring mechanical ventilation (non-invasive ventilation for sleep apnoea is allowed).
• Historical or current evidence of clinically significant uncontrolled disease which, in the opinion of the investigator, would put the safety of the subject at risk through participation or impact the study assessments or endpoints.
• Presence of an active implantable cardiac medical device (e.g., pacemaker or implantable cardioverter-defibrillator) or at a high risk for needing external defibrillation.
• History of skin hypersensitivity to adhesives.
• Current participation in a clinical trial which in the opinion of the investigator and GSK medical monitor might impact the objectives of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pilot and Core Study Phase; During Pilot phase,subjects will attend clinic at least once to perform a series of set reference tasks while wearing the accelerometer and electrode. Subjects will also continuously wear the accelerometer and electrode in their routine home-life setting for approximately 3 days after the clinic visit (home monitoring). During 48 week Core Study, subjects will attend 5 clinic visits to perform gold standard measures of function (ALS Functional Rating Scale-Revised and Forced Vital Capacity) and perform a series of set reference tasks while wearing the accelerometer and electrode. Subjects will also continuously wear the accelerometer and electrode in their routine home-life setting for approximately 3 days after the clinic visits (home monitoring). In between clinic visits, subjects will attach the accelerometer and electrode and wear it for approximately 3 days in their home. A telephone contact with the subject will be made by the site at the end of each 3-day home monitoring period

Device: Faros Sensor (FS) and LifeInsight Hub; Each subject will be issued one FS and a MAT LifeInsight Hub for use during the study. At each clinic visit in the Pilot and Core Study Phases, the Faros sensor will be placed on the subject just prior to the defined reference tasks and will be worn on the subject's sternum during completion of the tasks. The morning after the clinic visit, the subject will re-attach the sensor and wear it for approximately 3 days. In between visits during the Core Study Phase the subject will wear the FS every month for approximately 3 days to enable data collection on a monthly basis over the 48 week study period. Movement/physical activity data will be collected by the FS throughout the study.; Device: Fast Fix electrode patch; The Fast Fix electrode patch will be worn with the FS on the subject's sternum according to the same schedule as the FS. The Fast Fix electrode patch will be replaced by the subject on a daily basis during the 3 day monitoring period. Subjects will be provided instructions on how to operate and wear the Fast Fix electrode patch.; Procedure: Quantitative Measure of Speech (Core Phase Only); Subjects will follow simple prompts on a computer screen instructing them to say a series of vowels, words, and paragraphs which will be recorded using a high definition digital microphone and stored securely on a laptop. The speech waveform data will be sent via secure method to GSK/MAT for processing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Day Time Wear Time of the Device	Each participant was provided one accelerometer and electrode (Faros sensor and LifeInsight Hub) through which movement/physical activity data was collected throughout the study. Duration of day time wear time was calculated by adding the durations of the time spent [Active + lying + sedentary not lying] in the day time. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).NA indicates that data could not be calculated as participant number was <=1.	Up to Week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Night Time Wear Time of the Device	Each participant was provided one accelerometer and electrode (Faros sensor and LifeInsight Hub) through which movement/physical activity data was collected throughout the study. Duration of night time wear time was the calculated as the total of the times spent [Active + day time lying + day time "sedentary not lying"] for the night time. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data could not be calculated as participant number was <=1.	Up to Week 48
Average Time Spent Active	Number of minutes spent active per day and night over the 24-hour recording periods; averaged for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)	Up to Week 48
Average Time Spent 'Sedentary Not Lying'	Number of minutes spent 'sedentary not lying' per day and night for 24-hour recording period; averaged for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Average Time Spent Lying	Number of minutes spent lying per day and night over the 24-hour recording periods; averaged for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Average Time Spent Sedentary.	Number of minutes spent sedentary [time spent lying + time spent sedentary not lying] per day and night over the 24-hour recording periods; averaged for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Time Spent With Sensor Off	Sensor off time includes the time that the sensor was either switched off or the participant was not wearing it (or both). This outcome measure was planned but not performed.	Up to Week 48
Total Activity Count	Total activity count for the day time and night time for the 24-hour recording periods; averaged for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Maximum Activity Count in a 24 Hour Period	Maximum activity count for the day time and night time for the 24-hour recording periods; averaged for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)	Up to Week 48
Mean Maximum Activity Count in a 24 Hour Period	Mean maximum activity count of day time and night time for the 24-hour recording periods; averaged for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)	Up to Week 48
Number of Continuous Active Periods	Active periods were catagorized as >1minute to <=2minutes, >2 minutes to <=5minutes, >5 minutes to <=15 minutes, >15 minutes to <=30 minutes, >30 minutes. Total number of 'active periods were calculated as 1minute<x<2minutes + 'number of active periods 2minutes<x<5minutes + 'number of active periods 5minutes<x<15minutes + 'number of active periods 15minutes<x<30minutes + 'number of active periods >30minutes.	Up to Week 48
Percent of Time Lying Down at Night	Percent time spent lying per day and night over the 24-hour recording periods; averaged for each timepoint	Up to Week 48
Number of Night Time Movement Episodes Per Hour	Average number of night movement episodes per hour for each protocol time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Percent Time Night-time Rest Efficiency	Average night-time rest efficiency for each protocol time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)	Up to Week 48
Rest Fragmentation Index	Rest Fragmentation Index was computed as movement time (%) divided by number of movement episodes for each protocol time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Average Duration of Night Time Movement Episodes	Average duration of movement episodes for each time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Relationship Between Average Number Night Time Movements/Hour Versus Total ALSFRS-R	Estimates for between and within subject correlation coefficients were produced following multiple linear regression analyses on the actigraphy endpoints, comparing them with the ALSFRS-R total score and the gross motor domain and fine motor domain scores. Data for between subject correlation coefficient has been presented	Up to Week 48
Relationship Between Average Duration Movement Episodes at Night Versus Total ALSFRS-R	Estimates for between and within subject correlation coefficients were produced following multiple linear regression analyses on the actigraphy endpoints, comparing them with the ALSFRS-R total score and the gross motor domain and fine motor domain scores. Data for between subject correlation coefficient has been presented	Up to Week 48
Relationship Between Average Percent Time Night Time Rest Efficiency Versus Total ALSFRS-R	Estimates for between and within subject correlation coefficients were produced following multiple linear regression analyses on the actigraphy endpoints, comparing them with the ALSFRS-R total score and the gross motor domain and fine motor domain scores. Data for between subject correlation coefficient has been presented	Up to Week 48
Relationship Between Average Night Time Rest Fragmentation Index Versus Total ALSFRS-R	Estimates for between and within subject correlation coefficients were produced following multiple linear regression analyses on the actigraphy endpoints, comparing them with the ALSFRS-R total score and the gross motor domain and fine motor domain scores. Data for between subject correlation coefficient has been presented	Up to Week 48
Mean Heart Rate Variability (HRV) While Lying (Low Frequency[LF]/High Frequency[HF])	Mean Heart Rate Variability (HRV) averaged over 5 windows of lying down at each protocol time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Variance of HRV While Lying (LF/HF)	Variance of Heart Rate Variability (HRV) averaged over 5 windows of lying down at each protocol time point (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Mean HRV While Sedentary Not Lying (LF/HF)	Mean Heart Rate Variability (HRV) averaged over 5 windows of sedentary not lying at each protocol time point (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Variance of HRV While Sedentary Not Lying (LF/HF)	Variance of Heart Rate Variability (HRV) averaged over 5 windows of sedentary not lying at each protocol time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Mean HRV While Active (LF/HF)	Mean Heart Rate Variability (HRV) averaged over 5 windows of subjects being active at each protocol time point (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data is not available. Standard deviation could not be calculated when number of participants was <=1	Up to Week 48
Variance of HRV While Active (LF/HF)	Variance of Heart Rate Variability (HRV) averaged over 5 windows of subjects being active at each protocol time point (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data could not be calculated as participant number was <=1	Up to Week 48
Effect of Being Upright on HRV- Mean HRV (LF/HF Analysis)	The effect of being upright on mean HRV was calculated as [mean HRV while sedentary not lying minus mean HRV while lying] (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Effect of Being Upright on HRV Variance (LF/HF Analysis)	The effect of being upright on HRV variance was calculated as [HRV variance while sedentary not lying minus HRV variance while lying] (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Effect of Activity on Mean HRV (LF/HF)	The effect of activity on mean HRV was calculated as [mean HRV while sedentary not lying minus mean HRV while lying] (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data could not be calculated as participant number was <=1.	Up to Week 48
Effect of Activity on HRV Variance (LF/HF Analysis)	The effect of activity on HRV variance was calculated as [HRV variance while sedentary not lying minus HRV variance while lying] (LF/HF analysis). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data could not be calculated as participant number was <=1.	Up to Week 48
Mean HRV Over 24 Hours - Mean Root Mean Square of the Successive Differences (RMSSD)	Mean HRV over 24 hours (RMSSD analysis), averaged for each protocol time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
HRV Variance Over 24 Hours - Mean Root Mean Square of the Successive Differences (RMSSD) Analysis	HRV variance over 24 hours (RMSSD analysis), averaged for each protocol time point. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Relationship Between Absolute Values of HRV Endpoints (LF/HF) and Absolute Value of Total ALSFRS-R	Estimates for between and within subject correlation coefficients were produced following multiple linear regression analyses on the actigraphy endpoints, comparing them with the ALSFRS-R total score and the gross motor domain and fine motor domain scores. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that sample size was insufficient to calculate correlation coefficient	Up to Week 48
Measurement of Speech Quality	Speech quality was assessed by Central Tendency of Fundamental Frequency (CTF) F0, jitter, and shimmer for 'short ah' and 'long ah' tests. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Duration of Maximum Gap Between Words	Duration of maximum gap between words during running speech to planned to analyze quality of speech however; was not performed.	Up to Week 48
Speaking Rate	Speaking rate was analyzed during running speech. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Average Phoneme Rate	Phoneme rate was analyzed for the single word "doily". Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Maximum Phonation Time	Maximum phonation time for the single word "doily" test was analyzed for quality of speech testing. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Seconds
Percentage Pause Time	Percentage pause time for running speech was analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Relationship Between Absolute Values of Speech Endpoints and Absolute Value of ALSFRS-R	Mixed Model was used to calculate Repeated Measures Correlation Coefficients between the two variables when model is converged. The correlation coefficient among the repeated measurements is same for different variables. Multiple Linear Regression was used to calculate Within and Between Participant Correlation Coefficients when Mixed Model is not converged. Data for Repeated Measures Correlation Coefficient has been presented in the table below	Up to Week 48
Relationship Between Absolute Values of Speech Endpoints and Absolute Values of FVC	Mixed Model was used to calculate Repeated Measures Correlation Coefficients between the two variables when model is converged. The correlation coefficient among the repeated measurements is same for different variables. Multiple Linear Regression was used to calculate Within and Between Participant Correlation Coefficients when Mixed Model is not converged. Data for Between Subject Correlation Coefficient has been presented in the table below	Up to Week 48
Number of Participants Reporting Sensor Comfort	Participant's feedback on whether the sensor was comfortable to wear was categorized as "yes" and "no". Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Number of Participants Reporting Impact on Sleep	Participant feedback on how much the sensor impacted their sleep was categorized as "not at all", "moderately" and "minimally". Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Number of Participants With Ease of Setting up and Attaching the Sensor	The participants were required to give feedback on how easy was it to set up and/ or attach the sensor and it was categorized as "easy", "neutral" and "difficult". Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Number of Participants With Corresponding Activity Level Required to Complete Their Job	The activity level required by the participant to complete their job was recorded, and was categorized as Not working, Physical activity required, and Sedentary. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Number of Participants With Corresponding Average Activity Level During Time of Wearing the Sensor	Average activity level during the time of wearing the sensor was reported by the participants, and was categorized as very low level activity, low level activity, moderate level activity and high level activity. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Number of Participants Whose Sensor Fell Off	The participants reported whether the sensor fell off. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).	Up to Week 48
Number of Participants With Adverse Events Secondary to the Devices Used or Due to Study Procedures	Only those AEs and SAEs which, in the opinion of the investigator, were related to a protocol-mandated procedure or one of the devices used in the study were reported. An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE.	Up to Week 48
Type of Adverse Events Secondary to the Devices Used or Due to Study Procedures	Only those AEs and SAEs which, in the opinion of the investigator, were related to a protocol-mandated procedure or one of the devices used in the study were reported. An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. Number of AEs, SAEs and Adverse events leading to discontinuation (AELDs)from the study is presented	Up to Week 48

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Actual): December 26, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Biotelemetry
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 201283