The Relationship Between Arterial Stiffness and Respiratory Failure in Motor Neurone Disease

September 30, 2021 updated by: Guy's and St Thomas' NHS Foundation Trust

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SW3 6NP
        • Royal Brompton and Harefield NHS Trust
      • London, United Kingdom, SE1 7EH
        • Guys and St Thomas NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with Motor Neurone Disease

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Other: Non Invasive Ventilation
Assessments for those participants who are being set up onto NIV
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
Other: Without Non Invasive Ventilation
Assessments for those participants who are not being set up onto NIV

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
6 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison of pulse wave velocity values in MND patients to normal values
Time Frame: 6 weeks
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
6 weeks
Comparison of pulse wave velocity pre-post non invasive ventilation in MND patients
Time Frame: 6 weeks
Does NIV change pulse wave velocity in MND patients
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guy's and St Thomas' NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Patrick Murphy, Guys and St Thomas NHS Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 21, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 31, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 23, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 1, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 210214 16/LO/1560

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No individual participant data will be available

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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