Neuromuscular DiseasesNCT04100993
Multisystem and Autonomic Complications of NMD on Long-term NIV
An observational study of Neuromuscular Diseases and Neurologic Disorder, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This exploratory observational study evaluates autonomic function using measures including heart rate variability in adults with childhood-onset neuromuscular and neurological disorders (NMD) who use non-invasive ventilation (NIV) as part of their long-term care. Read more about this study
- Who is it for?
- Ages 16 years and olderHealthy volunteers can take part
- Conditions the study is for
- Neuromuscular Diseases, Neurologic Disorder
- How many people
- 35 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 25 Oct 2019to 20 May 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 16 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients with a relevant NMD who attend adult Sleep and Ventilation services at the study site will be identified by the direct care team. Healthy age- and sex-matched adults from the local community will be invited to participate by the research team.
Who may be able to join
- Patient group:
- Age ≥16 years
- Confirmed diagnosis of childhood-onset NMD
- Able and willing to provide informed consent
- Requires non-invasive ventilation on an intermittent or continuous basis to manage respiratory failure
- Reference group:
Show all 10Show fewer
- Age ≥16 years
- No significant co-morbidities
- Not on any regular medications
- Able and willing to provide informed consent
Who cannot join
- Inability to travel to hospital site
- Clinical instability or acute deterioration requiring hospitalisation or changes to medication in the previous 4 weeks
- A female of child-bearing potential who is pregnant or intends to become pregnant during study involvement
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Growing up on Non-invasive Ventilation: Assessment of Multisystem and Autonomic Complications of Neuromuscular and Neurological Disorders in Young Adults
This exploratory observational study evaluates autonomic function using measures including heart rate variability in adults with childhood-onset neuromuscular and neurological disorders (NMD) who use non-invasive ventilation (NIV) as part of their long-term care. Autonomic function will be correlated with measures of symptom burden, disease severity and complications.
Read the detailed description
Childhood-onset neuromuscular and neurological disorders (NMD) are a diverse group of rare conditions in which muscle function is significantly impaired. Due to progress in NMD management over recent decades, particularly the use of non-invasive ventilation (NIV) to treat chronic respiratory failure, many individuals are surviving into adulthood and even middle age. However, older individuals are developing potentially fatal complications related to the heart e.g. sudden cardiac death, gastrointestinal (GI) tract and increasing dependence on NIV.
Previous studies largely in children and adolescents suggest individuals with NMD may develop problems of the autonomic nervous system (ANS), a network of nerves vital to controlling the body's short-term responses to internal and external stimuli. It is likely some complications of NMD are related to ANS abnormalities.
This will be an exploratory observational study using a cross-sectional design in which non-invasive tools will be used to evaluate autonomic function during wake and sleep. Individuals over 16 years of age with a confirmed NMD diagnosis will be recruited. Derived parameters of autonomic function including heart rate variability will be compared to values from an exploratory reference group of age- and sex-matched healthy adults. Autonomic function will also be correlated to measures of symptom burden, complications, quality of life and disease severity. Qualitative methods will be used to further evaluate the experience and perceptions of adults with NMD in making decisions about their personal and medical care, which become more complex with increasing age and disease severity.
- Conditions
- Neuromuscular Diseases, Neurologic Disorder
- Being tested
- No intervention used
- Medical subject headings
- Neuromuscular Diseases, Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No intervention usedOther
No intervention used
| Study group | Role | What they receive |
|---|---|---|
| Patient group | 60 participants ≥16 years of age with a confirmed diagnosis of a childhood-onset NMD Receives: Other: No intervention used | |
| Exploratory reference group | 20 healthy adults ≥16 years of age Receives: Other: No intervention used |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate variability (HRV)
HRV will be analysed in time and frequency domains from short-term (5 minute) artefact free ECG recordings. Normal parameters will be determined from an age- and sex-matched exploratory reference group of healthy adults.
Measured: 1 day
Secondary outcomes (22)
Baroreflex sensitivity (BRS)
BRS will be analysed in time and frequency domains from short-term (5 minute) artefact free blood pressure recordings. Normal parameters will be determined from an age- and sex-matched exploratory reference group of healthy adults. This will be measured only in the patient participant group.
Measured: 1 day
Composite Autonomic Symptom Scale 31 questionnaire
Composite Autonomic Symptom Scale 31 questionnaire (COMPASS 31) is a validated questionnaire for quantitative assessment of autonomic symptoms, based on the original Autonomic Symptom Profile. The 31 questions are divided into seven domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor). The raw score from each domain is multiplied by a weight index to give a total score with a maximum score of 100 (minimum score 0). Higher scores indicate greater symptom burden.
Measured: 1 day
Sydney Swallow Questionnaire
The Sydney Swallow Questionnaire (SSQ) is a validated self-reported inventory of 17 questions measuring symptomatic severity of oral-pharyngeal dysphagia using 16 visual analogue scales (VAS) and one question scored on a Likert scale (0-5) to rate swallowing difficulty and symptoms of dysphagia and aspiration in a range of situations. Each VAS measures 100mm; the raw scores from these are added to the weighted score of the additional question to make the total possible raw score 1700 when the scores are added. Higher scores indicate greater symptom burden. This will be measured only in the patient participant group.
Measured: 1 day
The European Quality of Life - 5 Dimensions questionnaire
The European Quality of Life - 5 Dimensions questionnaire (EQ-5D-5L) is a standardised instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D-5L consists of a descriptive system comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, each with 5 levels of severity. An EQ visual analogue scale then asks patients how they feel on the day of the visit. A unique health state is defined by sequentially combining the indicated level in each of the 5 dimensions. This will be measured only in the patient participant group.
Measured: 1 day
Patient Assessment of Constipation Symptoms questionnaire
The Patient Assessment of Constipation Symptoms questionnaire (PAC-SYM) is a symptom inventory which measures specific symptoms of constipation in adults. It consists of a 12-item measure of patient's experience of symptoms and symptom severity. The score of each question is given equal weight and domain and total scores can be calculated by summing the relevant scores and dividing by the number of non-missing items. This will be measured only in the patient participant group.
Measured: 1 day
Individualized Neuromuscular Quality of Life Questionnaire
The Individualized Neuromuscular Quality of Life Questionnaire (INQoL) is a validated muscle disease specific measure use to assess health-related quality of life of adult patients with acquired or congenital neuromuscular diseases, developed from the experiences of patients with muscle disease. It consists of 45 questions within 10 sections. Four sections focus on the impact of key muscle disease symptoms; five assess at the degree and importance of impact muscle disease has on particular areas of life; one section asks about positive and negative effects of treatment. The questionnaire allows for variations in individual characteristics that influence quality of life. The scoring of the INQoL generates a profile and combining weighted scores of each domain produces a total score from 0 to 100, with higher scores indicate greater impact of disease. This will be measured only in the patient participant group.
Measured: 1 day
Severe Respiratory Insufficiency quality of life tool
The severe Respiratory Insufficiency quality of life tool (SRI)is a validated questionnaire assessing health-related quality of life in patients with respiratory failure on home ventilation. It consists of seven subscales covering 49 items rated on a 5-point Likert scale: respiratory complaints, physical functioning, attendant symptoms and sleep, social relationships, anxiety, psychological wellbeing and social functioning. After transformation and weighting of raw scores, a total score between 0 and 100 is calculated. Higher values indicate a better health-related quality of life. This will be measured only in the patient participant group.
Measured: 1 day
Forced Expiratory Volume in 1 second (FEV1)
The best of 3 attempts obtained through standard Spirometric assessment will be used to obtain FEV1 (L) in the patient participant group.
Measured: 1 day
Forced Expiratory Volume (FVC)
The best of 3 attempts obtained through standard Spirometric assessment will be used to obtain FVC (L) in the patient participant group.
Measured: 1 day
Ratio of FEV1/FVC
The values obtained from standard Spirometric assessment will be used to determine FEV1/FVC ratio in the patient participant group.
Measured: 1 day
Peak cough flow
Using a standard peak flow meter, peak cough flow will be recorded in L/min the patient participant group.
Measured: 1 day
Sniff nasal inspiratory pressure
Sniff nasal inspiratory pressure (SNIP) in each nostril will be recorded in the patient participant group.
Measured: 1 day
Brain natriuretic peptide
Serological brain natriuretic peptide (BNP) will be obtained through venepuncture in the patient participant group.
Measured: 1 day
Troponin-I
Serological troponin will be obtained through venepuncture in the patient participant group.
Measured: 6 months
Arterialised blood gas tensions
Standard blood gas tensions will be obtained from earlobe puncture in the patient participant group.
Measured: 1 day
Colon transit study
Single abdominal x-ray to evaluate number of retained radiopaque markers 5-days after oral ingestion in the patient participant group.
Measured: 1 day
Themes describing patient perceptions of experiences and needs in complex clinical and non-clinical decision making
Inductive thematic analysis of individual interviews to provide qualitative data in the patient participant group.
Measured: 1 hour
Weight
Measured using calibrated scales in kilograms
Measured: 1 day
Height
Measured using calibrated scales in centimetres
Measured: 1 day
Body Mass Index
Calculated using the formula BMI = weight(kg)/[height(m)]2
Measured: 1 day
Nocturnal transcutaneous carbon dioxide
Nocturnal transcutaneous carbon dioxide will be measured overnight in kilopascals (kPa)
Measured: 1 day
Cardiac function
Standard transthoracic echocardiogram will be performed in the patient participant group to assess cardiac function
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start25 Oct 2019
- Primary completion20 May 2021
- Study completion20 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuromuscular DiseasesStudies 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
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anita K Simonds, MD MBBS, Principal investigator, Royal Brompton & Harefield NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04100993
- Sponsor's protocol ID
- 266270
- Status last verified
- Oct 2024
- First submitted
- 31 Jul 2019
- Last updated
- 16 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Growing up on Non-invasive Ventilation: Assessment of Multisystem and Autonomic Complications of Neuromuscular and Neurological Disorders in Young Adults
- ClinicalTrials.gov ID
- NCT04100993
- Acronym / sponsor ID
- 266270
- Conditions
- Neuromuscular Diseases, Neurologic Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Study start
- 25 Oct 2019 (actual)
- Primary completion
- 20 May 2021 (actual)
- Study completion
- 20 May 2021 (actual)
- First posted
- 24 Sep 2019 (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.
This exploratory observational study evaluates autonomic function using measures including heart rate variability in adults with childhood-onset neuromuscular and neurological disorders (NMD) who use non-invasive ventilation (NIV) as part of their long-term care. Autonomic function will be correlated with measures of symptom burden, disease severity and complications.
Detailed description
Childhood-onset neuromuscular and neurological disorders (NMD) are a diverse group of rare conditions in which muscle function is significantly impaired. Due to progress in NMD management over recent decades, particularly the use of non-invasive ventilation (NIV) to treat chronic respiratory failure, many individuals are surviving into adulthood and even middle age. However, older individuals are developing potentially fatal complications related to the heart e.g. sudden cardiac death, gastrointestinal (GI) tract and increasing dependence on NIV.
Previous studies largely in children and adolescents suggest individuals with NMD may develop problems of the autonomic nervous system (ANS), a network of nerves vital to controlling the body's short-term responses to internal and external stimuli. It is likely some complications of NMD are related to ANS abnormalities.
This will be an exploratory observational study using a cross-sectional design in which non-invasive tools will be used to evaluate autonomic function during wake and sleep. Individuals over 16 years of age with a confirmed NMD diagnosis will be recruited. Derived parameters of autonomic function including heart rate variability will be compared to values from an exploratory reference group of age- and sex-matched healthy adults. Autonomic function will also be correlated to measures of symptom burden, complications, quality of life and disease severity. Qualitative methods will be used to further evaluate the experience and perceptions of adults with NMD in making decisions about their personal and medical care, which become more complex with increasing age and disease severity.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient group | – | Other: No intervention used60 participants ≥16 years of age with a confirmed diagnosis of a childhood-onset NMD |
| Exploratory reference group | – | Other: No intervention used20 healthy adults ≥16 years of age |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with a relevant NMD who attend adult Sleep and Ventilation services at the study site will be identified by the direct care team. Healthy age- and sex-matched adults from the local community will be invited to participate by the research team.
Key inclusion criteria (10 listed)
- Age ≥16 years
- Confirmed diagnosis of childhood-onset NMD
- Able and willing to provide informed consent
- Requires non-invasive ventilation on an intermittent or continuous basis to manage respiratory failure
- Age ≥16 years
Key exclusion criteria (3 listed)
- Inability to travel to hospital site
- Clinical instability or acute deterioration requiring hospitalisation or changes to medication in the previous 4 weeks
- A female of child-bearing potential who is pregnant or intends to become pregnant during study involvement
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 |
|---|---|---|
| No intervention usedNo intervention used | Other | Exploratory reference group, Patient group |
Primary outcome
Heart rate variability (HRV)
Time frame: 1 day
HRV will be analysed in time and frequency domains from short-term (5 minute) artefact free ECG recordings. Normal parameters will be determined from an age- and sex-matched exploratory reference group of healthy adults.
22 secondary outcomes
Baroreflex sensitivity (BRS)
Time frame: 1 day
Composite Autonomic Symptom Scale 31 questionnaire
Time frame: 1 day
Sydney Swallow Questionnaire
Time frame: 1 day
The European Quality of Life - 5 Dimensions questionnaire
Time frame: 1 day
Patient Assessment of Constipation Symptoms questionnaire
Time frame: 1 day
Individualized Neuromuscular Quality of Life Questionnaire
Time frame: 1 day
Severe Respiratory Insufficiency quality of life tool
Time frame: 1 day
Forced Expiratory Volume in 1 second (FEV1)
Time frame: 1 day
Forced Expiratory Volume (FVC)
Time frame: 1 day
Ratio of FEV1/FVC
Time frame: 1 day
Peak cough flow
Time frame: 1 day
Sniff nasal inspiratory pressure
Time frame: 1 day
Brain natriuretic peptide
Time frame: 1 day
Troponin-I
Time frame: 6 months
Arterialised blood gas tensions
Time frame: 1 day
Colon transit study
Time frame: 1 day
Themes describing patient perceptions of experiences and needs in complex clinical and non-clinical decision making
Time frame: 1 hour
Weight
Time frame: 1 day
Height
Time frame: 1 day
Body Mass Index
Time frame: 1 day
Nocturnal transcutaneous carbon dioxide
Time frame: 1 day
Cardiac function
Time frame: 1 day
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 16 Oct 2024.
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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.
Anita K Simonds, MD MBBS principal investigator
Royal Brompton & Harefield NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neuromuscular Diseases and Neurologic Disorder, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site 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 10 inclusion and 3 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 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Heart rate variability (HRV) (time frame: 1 day). 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 16 Oct 2024.