Multisystem and Autonomic Complications of NMD on Long-term NIV

Neuromuscular Diseases Clinical Trial

Official title:

Growing up on Non-invasive Ventilation: Assessment of Multisystem and Autonomic Complications of Neuromuscular and Neurological Disorders in Young Adults

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04100993
• Other study ID #: 266270
• Status: Recruiting
• Start date: October 25, 2019
• Est. completion date: October 11, 2021

Study information

• Verified date: March 2021
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: Lydia A Spurr, MBBS BMedSci
• Phone: 0207 352 8121
• Email: l.spurr[@]rbht.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical 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. Autonomic function will be correlated with measures of symptom burden, disease severity and complications.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 11, 2021
• Est. primary completion date: June 11, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

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:

• Age =16 years
• No significant co-morbidities
• Not on any regular medications
• Able and willing to provide informed consent

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Nervous System Diseases
• Neurologic Disorder
• Neuromuscular Diseases

Intervention

Other:
• No intervention used
No intervention used

Locations

Country	Name	City	State
United Kingdom	Royal Brompton Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	Ratio of FEV1/FVC	The values obtained from standard Spirometric assessment will be used to determine FEV1/FVC ratio in the patient participant group.	1 day
Secondary	Peak cough flow	Using a standard peak flow meter, peak cough flow will be recorded in L/min the patient participant group.	1 day
Secondary	Sniff nasal inspiratory pressure	Sniff nasal inspiratory pressure (SNIP) in each nostril will be recorded in the patient participant group.	1 day
Secondary	Brain natriuretic peptide	Serological brain natriuretic peptide (BNP) will be obtained through venepuncture in the patient participant group.	1 day
Secondary	Troponin-I	Serological troponin will be obtained through venepuncture in the patient participant group.	6 months
Secondary	Arterialised blood gas tensions	Standard blood gas tensions will be obtained from earlobe puncture in the patient participant group.	1 day
Secondary	Colon transit study	Single abdominal x-ray to evaluate number of retained radiopaque markers 5-days after oral ingestion in the patient participant group.	1 day
Secondary	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.	1 hour
Secondary	Weight	Measured using calibrated scales in kilograms	1 day
Secondary	Height	Measured using calibrated scales in centimetres	1 day
Secondary	Body Mass Index	Calculated using the formula BMI = weight(kg)/[height(m)]2	1 day
Secondary	Nocturnal transcutaneous carbon dioxide	Nocturnal transcutaneous carbon dioxide will be measured overnight in kilopascals (kPa)	1 day
Secondary	Cardiac function	Standard transthoracic echocardiogram will be performed in the patient participant group to assess cardiac function	1 day