Phase 1. Primary Objective: To evaluate the feasibility of the study procedures to measure breathing-task related cerebral activity using fMRI and respiratory (electro)physiological measures of breathing. Phase 2. Primary Objective: To identify…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Breathing-task related cerebral activity as a function of breathing condition
(rest, paced and loaded) and disease (with or without myotonic dystrophy).
Secondary outcome
Other MRI measures
- T1 structural scan- focal/general (ROI) atrophy with voxel-based measuring of
cerebral cortex volume
- T2 structural scan- focal/general (ROI) atrophy with voxel-based measuring of
cerebral cortex volume
- Resting state functional connectivity (seed regions, derived from breathing
related fMRI)
Physiological measurements inside MRI
- Breathing rate, and depth is recorded using an pneumotachograph that records
airway flow.
- Oxygen and carbon dioxide content in expired air is measured using a gas
sampling module.
- Electrodermal activity (EDA): EDA is a measure of sympathetic autonomic
nervous system activation and is measured using Ag/AgCI electrodes placed on
the palmar surface of the hand or distal phalanges.
- Heart rate (HR): HR is measured using electrocardiography (ECG) using 3 lead
electrodes attached to the skin surface, or using a pulse oximeter
(photoplethysmograph) affixed to a finger.
- Tracking of eye gaze and pupil diameter: eye tracking is used to inform
analyses about the participant's gaze position and saccade latencies. Pupil
diameter is used as a measure of sympathetic arousal.
- Surface electromyography (EMG): EMG is measured using Ag/AgCI electrodes
place on the skin over muscles of interest (diaphragm and intercostal muscles).
Physiological measurements outside MRI
- Pulmonary function testing: forced vital capacity, force expiratory volume in
1 second, maximal inspiratory pressure and maximal expiratory pressure will be
determined using a hand-held device.
- Hypercapnic ventilatory response curve (HCVR): HCVR will be determined using
the CO2-rebreathing technique.
- Respiratory related evoked potential (RREP): RREP is a measure of cerebral
cortical activity elicited by a short inspiratory occlusion.
- Transcranial magnetic stimulation (TMS) diaphragm: TMS is an established tool
for investigating the corticospinal pathways involved in the control of
breathing.
Background summary
Myotonic dystrophy type I is a neuromuscular disease and the most common form
of muscular dystrophy in adults. Patients with myotonic dystrophy commonly
experience significant breathing problems that can lead to respiratory failure
or require mechanical ventilation. Moreover, respiratory failure is the leading
cause of death in myotonic dystrophy. However, the exact pathophysiology of
respiratory failure in myotonic dystrophy is unknown. The complex process of
neural control of breathing may be involved, but is understudied. In part, this
is caused by methodological limitations to assess breathing related cerebral
activity. In this study, we will test the feasibility of advanced techniques
(functional MRI and respiratory (electro)physiological techniques) to measure
breathing-task related cerebral activity and perform a pilot study to test the
hypothesis that the functional architecture of the cerebral network controlling
breathing is impaired in patients with myotonic dystrophy type I. More
specifically, we expect that patients with myotonic dystrophy show reduced
breathing-task related cerebral activity in response to respiratory stimuli
compared to healthy subjects.
Study objective
Phase 1. Primary Objective: To evaluate the feasibility of the study procedures
to measure breathing-task related cerebral activity using fMRI and respiratory
(electro)physiological measures of breathing. Phase 2. Primary Objective: To
identify disease (myotonic dystrophy) specific alterations in breathing-task
related cerebral activity. Secondary Objective: To explore the relation between
fMRI measures and respiratory (electro)physiological measures of cerebral
breathing activity.
Study design
Exploratory cross-sectional study.
Study burden and risks
The risk of this study for the participants is negligible. Subjects do not
directly benefit from participating in this study. The scientific benefit of
this study is to achieve a better understanding of the neural control of
breathing in myotonic dystrophy. The outcomes of this study may give rise to
future new treatments for myotonic dystrophy. The burden of the separate study
procedures are relatively small: there are no invasive procedures. However, the
total time of the visit and the collective burden of the experiments may be
perceived as strenuous. Therefore, subjects will be explicitly informed about
this aspect of the study, and enough breaks will scheduled in the program.
Reinier Postlaan 4
Nijmegen 6525GC
NL
Reinier Postlaan 4
Nijmegen 6525GC
NL
Listed location countries
Age
Inclusion criteria
• Healthy subjects: competent adult volunteers
• Patients: genetically-confirmed adult patients with myotonic dystrophy
• Normal or corrected-to-normal vision
• Normal uncorrected hearing
• Willingness and ability to understand nature and content of the study
• Ability to participate and comply with study requirements
Exclusion criteria
• History of or current psychiatric treatment
• History of or current brain surgery or epilepsy
• Pregnancy
• MRI incompatibility (metal parts in upper body, implants, medical devices or
medicinal plasters)
• TMS incompatibility (metal parts in head, skin allergies)
• Claustrophobia
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL75853.091.20 |