Motor Neurone DiseaseNCT03444428
The Relationship Between Arterial Stiffness and Respiratory Failure in Motor Neurone Disease
An observational study of Motor Neurone Disease and Hypoxemia and/or Hypercapnia, run by Guy's and St Thomas' NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
Patients with Motor Neurone Disease (MND) admitted to Lane Fox Unit /Royal Brompton Hospital and/or reviewed in Lane Fox Unit /Royal Brompton Hospital clinics and/or outreach review will be approached for participation in the study Physiological assessment and measurement of arterial stiffness will be performed in all… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Motor Neurone Disease, Hypoxemia and/or Hypercapnia
- What is being tested?
- Non Invasive Ventilation and Without Non Invasive Ventilation
- How many people
- 13 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 21 Feb 2017to 30 Jun 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with Motor Neurone Disease
Who may be able to join
- MND diagnosis
- The ability to perform the respiratory function testing satisfactorily
- Stable clinical and functional state for at least four weeks before testing
- BMI 20-30 kg•m-2
Who cannot join
- Pregnancy
- Aged <18, >80
- Significant physical or psychiatric comorbidity that would prevent compliance with trial protocol
- Unstable clinical state
- Use of mechanical ventilation
- Cardiovascular disorders (history, physical examination)
Show all 11Show fewer
- Known lung disease, such as asthma or COPD or any other cause of hypoxemia and/or hypercapnia but MND (history, physical examination, CXR review [High Resolution Computed Tomography if CXR is not compatible with neuromuscular disease alone])
- Airway obstruction (FEV1/FVC<0.75)
- Diabetes mellitus
- Obesity (BMI>30 kg•m-2)
- Smoking history (>10 pack∙years or active smoker)
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Guys and St Thomas NHS Trust
London, SE1 7EH
Royal Brompton and Harefield NHS Trust
London, SW3 6NP
About this study
Official title: The Relationship Between Arterial Stiffness and Respiratory Failure: Using Motor Neurone Disease as a Paradigm to Assess the Consequence of Sleep Disordered Breathing on Arterial Stiffness
- Patients with Motor Neurone Disease (MND) admitted to Lane Fox Unit /Royal Brompton Hospital and/or reviewed in Lane Fox Unit /Royal Brompton Hospital clinics and/or outreach review will be approached for participation in the study
- Physiological assessment and measurement of arterial stiffness will be performed in all patients at baseline and after the use of non invasive ventilation for 6 weeks.
- MND patients not requiring mechanical ventilation will serve as controls since non invasive ventilation cannot be withheld from MND patients in type II respiratory failure.
- Data will be analysed to look for differences between groups, relationships in baseline or change from baseline in respiratory physiological measures, inflammatory indices, breathlessness, and arterial stiffness.
- Age, Height, Weight
- History and Physical Examination
- Evaluation of dysponea: mMRC, Borg Scale (Seated-Supine)
- Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R)
- Sleep Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ-5)
- 24 hour blood pressure monitor
- Carotid-femoral pulse wave velocity
- Respiratory Muscle Strength - Maximal Inspiratory Pressure, Maximal Expiratory Pressure, and Sniff Nasal Inspiratory Pressure
- Spirometry - FEV1 and FVC
- Arterial Blood Gas
- CRP and fibrinogen (clinically)
- Breathe CO exhale
Read the detailed description
The stiffness of the arterial wall is highly relevant to cardiovascular disease. Large elastic arteries and smaller muscular conduit arteries become stiffer with ageing, a process that is accelerated in the presence of cardiovascular disease. Arterial stiffness increases also with various disease states, including hypertension, diabetes mellitus, obesity, smoking, hypercholesterolemia, and kidney disease. Numerous techniques have been developed to measure arterial stiffness, either in single vessels or in entire muscular arterial trees. These techniques have increasingly been shown to improve stratification of cardiovascular risk and risk reduction beyond that provided by conventional risk factors. Furthermore, large artery stiffness, measured via carotid-femoral pulse wave velocity, independently predicts the risk of cardiovascular events in both clinical and community-based cohorts.
Abnormalities in arterial stiffness have been noted in disorders characterized by hypoxia with or without hypercapnia. These abnormalities could be driven by the risk factors for those conditions (e.g. cigarette smoke, obesity). In COPD, all studies are consistent showing a significant increase in arterial stiffness compared with ex-smokers without airway obstruction and nonsmoker healthy control subjects. The severity of airway obstruction is consistently related to arterial stiffness in COPD. Furthermore, airflow limitation arising from cigarette smoking, but not airflow limitation in non-smokers, was associated with arterial stiffness in a general population independently of established risk factors. The presence of OSA was associated with higher arterial stiffness indices independent of major confounders. In this context, OSA is associated with increased arterial stiffness independent of blood pressure.
Non invasive ventilation has been shown to reduce arterial stiffness in obstructive sleep apnea. In particular, there are studies that have examined the impact of continuous positive airway pressure (CPAP) on arterial stiffness (measured with pulse wave velocity) in OSA patients. Other studies have examined changes in arterial stiffness (measured with other than pulse wave velocity method) after treatment of OSA with CPAP. Furthermore, to the best of our knowledge no investigation exists on the impact of non invasive bilevel positive airway pressure ventilation on arterial stiffness in neuromuscular disease.
The Lane Fox Unit, the UK's largest weaning, rehabilitation and home ventilation unit, is treating neuromuscular patients. In neuromuscular disease, especially in MND, confounding factors as obesity, cigarette smoke, hypertension, and diabetes mellitus can be excluded. This gives the opportunity to determine whether hypoxemia and/or hypercapnia alone cause arterial stiffness. Furthermore, in this pilot study it will be investigated whether non invasive ventilation has any effect on arterial stiffness in MND patients.
- Being tested
- Non Invasive Ventilation, Without Non Invasive Ventilation
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non Invasive VentilationOther
Assessments for those participants who are being set up onto NIV
Without Non Invasive VentilationOther
Assessments for those participants who are not being set up onto NIV
| Study group | Role | What they receive |
|---|---|---|
| Non Invasive Ventilation | * Age, height, weight
* History and Physical Examination
* Evaluation of dyspnoea: mMRC, Borg scale (Seated-Supine)
* Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R)
* Sleep-Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ-5)
* 24h Blood Pressure monitor
* Spirometry - FEV1 and FVC
* Respiratory muscle strength - MIP, MEP, and SNIP
* Arterial Blood Gases
* Carotid-femoral pulse wave velocity
* Breath CO exhale Receives: Other: Non Invasive Ventilation | |
| Without Non Invasive Ventilation | Age, height, weight
* History and Physical Examination
* Evaluation of dyspnoea: mMRC, Borg scale (Seated-Supine)
* Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R)
* Sleep-Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ-5)
* 24h Blood Pressure monitor
* Spirometry - FEV1 and FVC
* Respiratory muscle strength - MIP, MEP, and SNIP
* Arterial Blood Gases
* Carotid-femoral pulse wave velocity
* Breath CO exhale Receives: Other: Without Non Invasive Ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparing the pulse wave velocity between MND patients with hypoxemia and/or hypercapnia to those MND Patients that do not have hypoxemia and/or hypercapnia
Is there a difference in pulse wave velocity between patients with MND who have and those who do not have hypoxemia and/or hypercapnia
Measured: 6 weeks
Secondary outcomes (2)
Comparison of pulse wave velocity values in MND patients to normal values
To clarify if there is an increased pulse wave velocity in MND patients and quantify whether patients are within predicted values or not against current evidenced literature
Measured: 6 weeks
Comparison of pulse wave velocity pre-post non invasive ventilation in MND patients
Does NIV change pulse wave velocity in MND patients
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2018
- Study start21 Feb 2017
- Primary completion30 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Motor Neurone DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick Murphy, Principal investigator, Guys and St Thomas NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03444428
- Sponsor's protocol ID
- 210214 16/LO/1560
- Status last verified
- Sep 2021
- First submitted
- 31 Jul 2017
- Last updated
- 1 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No individual participant data will be available
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Arterial Stiffness and Respiratory Failure: Using Motor Neurone Disease as a Paradigm to Assess the Consequence of Sleep Disordered Breathing on Arterial Stiffness
- ClinicalTrials.gov ID
- NCT03444428
- Acronym / sponsor ID
- 210214 16/LO/1560
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Guy's and St Thomas' NHS Foundation TrustUniversity, hospital or other
- Study start
- 21 Feb 2017 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 23 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Patients with Motor Neurone Disease (MND) admitted to Lane Fox Unit /Royal Brompton Hospital and/or reviewed in Lane Fox Unit /Royal Brompton Hospital clinics and/or outreach review will be approached for participation in the study
- Physiological assessment and measurement of arterial stiffness will be performed in all patients at baseline and after the use of non invasive ventilation for 6 weeks.
- MND patients not requiring mechanical ventilation will serve as controls since non invasive ventilation cannot be withheld from MND patients in type II respiratory failure.
- Data will be analysed to look for differences between groups, relationships in baseline or change from baseline in respiratory physiological measures, inflammatory indices, breathlessness, and arterial stiffness.
- Age, Height, Weight
- History and Physical Examination
- Evaluation of dysponea: mMRC, Borg Scale (Seated-Supine)
- Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R)
- Sleep Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ-5)
- 24 hour blood pressure monitor
- Carotid-femoral pulse wave velocity
- Respiratory Muscle Strength - Maximal Inspiratory Pressure, Maximal Expiratory Pressure, and Sniff Nasal Inspiratory Pressure
- Spirometry - FEV1 and FVC
- Arterial Blood Gas
- CRP and fibrinogen (clinically)
- Breathe CO exhale
Detailed description
The stiffness of the arterial wall is highly relevant to cardiovascular disease. Large elastic arteries and smaller muscular conduit arteries become stiffer with ageing, a process that is accelerated in the presence of cardiovascular disease. Arterial stiffness increases also with various disease states, including hypertension, diabetes mellitus, obesity, smoking, hypercholesterolemia, and kidney disease. Numerous techniques have been developed to measure arterial stiffness, either in single vessels or in entire muscular arterial trees. These techniques have increasingly been shown to improve stratification of cardiovascular risk and risk reduction beyond that provided by conventional risk factors. Furthermore, large artery stiffness, measured via carotid-femoral pulse wave velocity, independently predicts the risk of cardiovascular events in both clinical and community-based cohorts.
Abnormalities in arterial stiffness have been noted in disorders characterized by hypoxia with or without hypercapnia. These abnormalities could be driven by the risk factors for those conditions (e.g. cigarette smoke, obesity). In COPD, all studies are consistent showing a significant increase in arterial stiffness compared with ex-smokers without airway obstruction and nonsmoker healthy control subjects. The severity of airway obstruction is consistently related to arterial stiffness in COPD. Furthermore, airflow limitation arising from cigarette smoking, but not airflow limitation in non-smokers, was associated with arterial stiffness in a general population independently of established risk factors. The presence of OSA was associated with higher arterial stiffness indices independent of major confounders. In this context, OSA is associated with increased arterial stiffness independent of blood pressure.
Non invasive ventilation has been shown to reduce arterial stiffness in obstructive sleep apnea. In particular, there are studies that have examined the impact of continuous positive airway pressure (CPAP) on arterial stiffness (measured with pulse wave velocity) in OSA patients. Other studies have examined changes in arterial stiffness (measured with other than pulse wave velocity method) after treatment of OSA with CPAP. Furthermore, to the best of our knowledge no investigation exists on the impact of non invasive bilevel positive airway pressure ventilation on arterial stiffness in neuromuscular disease.
The Lane Fox Unit, the UK's largest weaning, rehabilitation and home ventilation unit, is treating neuromuscular patients. In neuromuscular disease, especially in MND, confounding factors as obesity, cigarette smoke, hypertension, and diabetes mellitus can be excluded. This gives the opportunity to determine whether hypoxemia and/or hypercapnia alone cause arterial stiffness. Furthermore, in this pilot study it will be investigated whether non invasive ventilation has any effect on arterial stiffness in MND patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non Invasive Ventilation | – | Other: Non Invasive Ventilation* Age, height, weight * History and Physical Examination * Evaluation of dyspnoea: mMRC, Borg scale (Seated-Supine) * Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) * Sleep-Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ-5) * 24h Blood Pressure monitor * Spirometry - FEV1 and FVC * Respiratory muscle strength - MIP, MEP, and SNIP * Arterial Blood Gases * Carotid-femoral pulse wave velocity * Breath CO exhale |
| Without Non Invasive Ventilation | – | Other: Without Non Invasive VentilationAge, height, weight * History and Physical Examination * Evaluation of dyspnoea: mMRC, Borg scale (Seated-Supine) * Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) * Sleep-Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ-5) * 24h Blood Pressure monitor * Spirometry - FEV1 and FVC * Respiratory muscle strength - MIP, MEP, and SNIP * Arterial Blood Gases * Carotid-femoral pulse wave velocity * Breath CO exhale |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with Motor Neurone Disease
Key inclusion criteria (4 listed)
- MND diagnosis
- The ability to perform the respiratory function testing satisfactorily
- Stable clinical and functional state for at least four weeks before testing
- BMI 20-30 kg•m-2
Key exclusion criteria (11 listed)
- Pregnancy
- Aged <18, >80
- Significant physical or psychiatric comorbidity that would prevent compliance with trial protocol
- Unstable clinical state
- Use of mechanical ventilation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non Invasive VentilationAssessments for those participants who are being set up onto NIV | Other | Non Invasive Ventilation |
| Without Non Invasive VentilationAssessments for those participants who are not being set up onto NIV | Other | Without Non Invasive Ventilation |
Primary outcome
Comparing the pulse wave velocity between MND patients with hypoxemia and/or hypercapnia to those MND Patients that do not have hypoxemia and/or hypercapnia
Time frame: 6 weeks
Is there a difference in pulse wave velocity between patients with MND who have and those who do not have hypoxemia and/or hypercapnia
2 secondary outcomes
Comparison of pulse wave velocity values in MND patients to normal values
Time frame: 6 weeks
Comparison of pulse wave velocity pre-post non invasive ventilation in MND patients
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2021.
- Individual participant dataSharing planned: No. No individual participant data will be available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Murphy principal investigator
Guys and St Thomas NHS Foundation Trust
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Motor Neurone Disease and Hypoxemia and/or Hypercapnia, run by Guy's and St Thomas' NHS Foundation Trust at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparing the pulse wave velocity between MND patients with hypoxemia and/or hypercapnia to those MND Patients that do not have hypoxemia and/or hypercapnia (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2021.