Clinical trial NCT03764384: Validation Of Tidal/End -Tidal CO2 in ALS
Official title: An Observational Study in People With Amyotrophic Lateral Sclerosis to Validate Tidal /End-Tidal CO2, Measured by the N-Tidal C™ Against Directly Measured PaCO2 and to Determine the Ease of Home Use of the Device
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Keywords: PaCO2
N-Tidal C Device
Self-monitoring
CO2 waveforms
Lead sponsor: Papworth Hospital NHS Foundation Trust
Sponsor class: OTHER_GOV
Collaborators: name: Motor Neurone Disease Association
name: Innovate UK
name: DOCATEF
name: TidalSense
First posted: 2018-12-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will have previously been diagnosed with Motor Neurone Disease by a neurologist. Study participants will be recruited from patients attending weekly Motor Neurone Disease clinics within the RSSC at Royal Papworth Hospital.

Brief summary: The study team propose that a new, hand-held test device may be valuable in the management of breathing failure in patients with Motor Neurone Disease (MND). The study team need to validate this device against the current gold standard of blood gas analysis and determine whether people with MND can use it at home. The new device, called 'N-Tidal C™' measures the carbon dioxide (CO2) in expired breath. At the end of the breath (end tidal) the CO2 level gives an indication of the CO2 in the person's arterial blood. Ventilatory failure is diagnosed at present using the value of CO2 in the arterial blood, but usually this can only be measured in specialist clinics. The study will determine if the end tidal CO2 measured by the new device agrees with CO2 measured on a blood test in clinic and also whether or not the device is practical for home use. The team will analyse the output of the device during home monitoring to see if changes in the pattern of CO2 in the expired breath identify, or even predict, the development of breathing failure in the community. With the results of these measures and detailed information about the patients in Papworth's clinic, recruited to this study, collected over a year the team will design a follow on study to see if using the new device at home can improve survival and quality of life for people with MND.

Detailed description: This is a prospective, observational study of patients attending Royal Papworth Hospital's weekly MND clinic. If a patient decides to participate in the study, they will continue to receive all normal care. Researchers will ask permission to review the results of any medical investigations and tests previously undertaken, by looking in medical records and will collect new data prospectively. There will be two groups of patients recruited:

A).Hospital Questionnaire Monitoring Group (12 months) for up to 200 patients who will:

i) Have four routine hospital based assessments (every 3 months, standard care) ii) Above usual care: completion of the ALSFRS-R questionnaire at each clinic (4 in total. The ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score-Revised) measures range of difficulties that people with MND can have in their daily lives. The results from this questionnaire help to measure the severity of MND symptoms, and how fast the disease is progressing. B). Home Device Monitoring Group (12-24 months) for 30 patients These participants patient will be given a portable monitoring device (called the N-Tidal C) to record their breathing pattern in clinic and at home and have: i) Four to six routine hospital based assessments (every 3 months, standard care). At the discretion of the investigator this may be at each clinic visit up to a total of 24 months ii) Completion of an ALSFRS-R symptom questionnaire at each visit (4-6 in total). At the discretion of the investigator this may be at each clinic visit up to a total of 24 months iii) Telephone consultation 2 weeks after commencing home monitoring to validate correct and safe use of the device (1 in total) iv) Completion of a supervised N-Tidal C breath record at each clinic visit (4 to 6 total). At the discretion of the investigator this may be at each clinic visit up to a total of 24 months v) Completion of a weekly symptom diary (up to 52 in total). At the discretion of the investigator this may continue up to 24 months vi) Home monitoring with N-Tidal C for 75 seconds, up to 3 times per day (up to study finish). SA 02 introduced an additional modified breath holding manoeuvre for home monitoring patients in clinic.

The range of 4 to 6 assessments covers the eventuality that participants may start in group A and transfer to group B as their condition changes. This will be determined by the treating doctor and will be based upon their lung function, limb weakness and whether they (or a carer) are able to use the device. During the home monitoring trial, data collected by the N-Tidal C device will be downloaded at each clinic visit, to check that the device is correctly recording data. Researchers will not be able to analyse the data collected by the device.

Only the information obtained from the standard measurements (standard care) will be used to decide when a patient needs help with their breathing at night time by starting a ventilator. A patient participating in the Home Monitoring Group will continue to use their N-Tidal C device to record their daytime breathing up to 3 times per day, after they start using a ventilator.

Eligibility criteria: Inclusion Criteria:

- 1. Male or female with a diagnosis of definite or probable Motor Neurone Disease according to El Escorial criteria.

2. Willing and able to provide informed consent.

Exclusion Criteria:

1. Lung, chest wall, neuromuscular, cardiac or other comorbidity or abnormality that would markedly affect spirometry and/or other measures of lung function or TBCO2 measurements. To be judged by the CI.
2. Tracheostomy in situ

Additional Eligibility Criteria for Home Monitoring patients Patients invited to use the N-Tidal CTM data collecting device within the study would be selected using the following additional inclusion criteria. These patients in theory would be most likely to get reliable results from the capnometer, be candidates for NIV, and to reach one of the study end-points within the follow-up period.

Home monitoring Inclusion Criteria:

1. Not in ventilatory failure at the start of the study (PaCO2 \< 6.0 KPa)
2. Sufficient manual dexterity and arm strength to use the device (or have a live-in carer/spouse/family member able to assist and willing to do so).
3. Verified able to use the device (by trial with dummy device).
4. Stated intention at the start of the study that they will accept NIV if they develop ventilatory failure.

Home Monitoring Exclusion Criteria

1. In the opinion of the clinical investigator, the participant would have difficulty completing the study procedures consistently.
2. Established on NIV treatment

Primary outcomes:
measure: The primary outcome of interest is the degree of agreement between end tidal CO2 measured by the N-Tidal CTM device and PaCO2 from arterial blood gas analysis.
timeFrame: At each clinic visit through to study completion up to 24 months
Secondary outcomes:
measure: Identify when an MND patient requires additional support with their breathing, in the form of starting NIV as derived from the CO2 measurement (kPA) and Respiratory Rate (RR) per minute from the N-Tidal CTM device.
timeFrame: At each clinic visit through to study completion up to 24 months
measure: Identify when an MND patient develops a treatable respiratory condition, such as an infection as derived from the CO2 measurement (kPA) and Respiratory Rate (RR) per minute from the N-Tidal CTM device..
timeFrame: At each clinic visit through to study completion up to 24 months
Other outcomes:
measure: Any adverse events (AEs) reported during performing the study procedures
timeFrame: At each clinic visit through to study completion up to 24 months
measure: Any adverse device events (ADEs
timeFrame: At each clinic visit through to study completion up to 24 months
measure: Visual analogue scale (VAS) to record 'ease of use' of the N-Tidal C™ device during the study and at study completion
timeFrame: At each clinic visit through to study completion up to 24 months
Locations:
city: Papworth Everard
country: United Kingdom
facility: Royal Papworth NHS Foundation Trust
state: Cambridge
Study officials:
affiliation: Royal Papworth NHS Hospital
name: Ian E Smith, MA MD F.R.C.P
role: PRINCIPAL_INVESTIGATOR
References:
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citation: COPD clinical trial : NIHRCRN 19599, ISRCTN 56492264
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citation: Banerjee SK, Davies M, Sharples L, Smith I. The role of facemask spirometry in motor neuron disease. Thorax. 2013 Apr;68(4):385-6. doi: 10.1136/thoraxjnl-2012-201804. Epub 2012 Jul 27. No abstract available.