TRICALS Respiratory Registry

Study titleTRICALS Research Into the Course of ALS Registry: A multi-centre study of respiratory decline and associated symptoms in people with ALS/MND
UK Chief InvestigatorProfessor Chris McDermott
Research summaryMotor neurone disease is a life shortening disorder, in which the nerves that connect the muscles to the nervous system die. This leads to a progressive weakness of the muscles needed for movement of the arms and legs, chewing and swallowing, and breathing. Usually individuals affected by MND succumb to the illness and die within 2-3 years. There is no cure and treatment is aimed at easing symptoms.
Therapies that improve breathing have the potential to improve both quality of life, and possibly survival. This is evidenced by the beneficial effect of NIV (airway support) on survival (up to 9 months). Drugs that enhance breathing muscle strength therefore have the potential to significantly enhance quality of life and survival, both by delaying the time to introduction of NIV, and by enhancing cough and secretion management. However, definitive measures that evaluate the impact of changes in lung efficiency and the ability to cough are lacking. This is a barrier to the development and identification of effective new treatments improving breathing muscle strength.
The overall aim of this study is to identify the most appropriate outcome measures to detect meaningful clinical differences in breathing and cough muscle strength which can be used in future studies to evaluate the effectiveness of new treatments.
We aim to recruit 300 patients from six MND clinics around Europe. We will carry out four respiratory assessments: sniff nasal inspiratory press (SNIP); slow vital capacity (SVC); forced vital capacity (FVC); and peak cough flow (PCF). We will administer questionnaires to assess respiratory symptoms, quality of life, sleep, fatigue, secretion management, and caregiver burden. Patients will be followed up for 18 months at 3 monthly intervals. We will also contact patients remotely every 2 weeks to record the details of any chest infections.
Inclusion/exclusion criteriaINCLUSION CRITERIA
- Kings stage 2 or 3 (prior to respiratory failure but likely encounter respiratory symptoms during 18 month data collection period);
- Ability to give informed consent;
- Ability to complete respiratory function measurement as defined by the ability to generate consistent scores on SVC/FVC (2 valid scores within 10%);
- Ability to correspond remotely by email/text message/telephone independently or with the assistance of a carer.

EXCLUSION CRITERIA
- Frontotemporal dementia;
- Diagnosis of another respiratory condition requiring current active management (e.g. Asthma, COPD, bronchiectasis, lung cancer);
- Use of NIV at time of enrolment (Kings Stage 4).
Current statusActive – recruiting
LocationsSheffield
King's College Hospital, London
Contact detailsLead site: Kate Lavender
0114 271 3339 Email: Katharine.Lavender@sth.nhs.uk
Recruitment group(s)Patients with MND
Recruitment target(s)50 participants per site (100 in UK); 300 participants globally.
Key datesActual opening date: 06 December 2018
Recruitment planned end date: 31 December 2019
Funder(s)Cytokinetics, Inc.
SponsorUK Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
Study designObservational
Intervention (if applicable)Not applicable
Phase (if applicable)Not applicable
Outcome measuresThe primary outcome is to describe the rates of decline across a range of respiratory function constructs.

Secondary outcomes:
1. Examine the relationships between rates of decline in respiratory function measures and prognosis
2. Correlate rates of decline in respiratory function measures and the ALS-FRS-R
3. Examine the respiratory tract infection morbidity rates
4. Examine the relationship between respiratory tract infection morbidity and respiratory function
5. Explore the potential relationships between other demographic characteristics, baseline variables, and outcome measures as defined above.
Publications / Results reportsLinks will be provided when papers are published.
Participant Information Sheet