The primary aim is to study if systemic or cerebral reactivity in DMD patients differs from healthy age-matched controls, to determine whether 1) cerebral autoregulation or 2) systemic blood pressure underlies the reduced cerebral perfusion in DMD.…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary end-points of this study are differences in systemic blood
pressure, global cerebral blood flow velocity and local cerebral perfusion
between healthy controls and patients with DMD.
Secondary outcome
- Systolic / diastolic blood pressure
- Heart rate
- Total peripheral resistance
- End-tidal CO¬2 content (PetCO¬2)
- Blood volume shift
- Sustained attention to response task score and regional brain blood flow
response
- General intellectual function based on PPVT
- Response time and pressing endurance measured with FePsy
- Cardiac function: stroke volume and shortening fraction of left ventricle
Background summary
Duchenne muscular dystrophy (DMD) is characterized by severe and progressive
muscle weakness due to mutations in the DMD gene which lead to the absence of
the dystrophin protein. A significant proportion of the affected children
suffer from specific learning and behavioral disabilities which are more common
with distal mutations in the DMD gene that lead to absence of multiple
dystrophin isoforms. Recently we reported a reduction in the amount of grey
matter volume, altered white matter microstructure and reduced cerebral blood
flow, assessed with magnetic resonance imaging (MRI) in DMD. Cerebral blood
flow plays an important role in cognitive functioning and is potentially
amenable to treatment. Therefore, we aim to explore the mechanism underlying
the reduced perfusion in DMD.
Study objective
The primary aim is to study if systemic or cerebral reactivity in DMD patients
differs from healthy age-matched controls, to determine whether 1) cerebral
autoregulation or 2) systemic blood pressure underlies the reduced cerebral
perfusion in DMD. The secondary aim is to study if changes in cerebral
autoregulation are regional or global in nature.
Study design
We postulate that either cerebral autoregulation is disturbed or systemic blood
pressure is reduced. We will use a two-step approach in an observational study
design: (1) we will assess the response to orthostatic change using continuous
transcranial Doppler (TCD) and finger plethysmography to monitor systemic and
global cerebral blood flow velocity during head-up tilt (HUT). (2) We will
quantify local cerebral blood flow using MRI during resting conditions and
during two different tasks, one motor independent test that only targets the
visual cortex, and one cognitive sustained attention task that involves
multiple brain regions to study regional changes in cerebral autoregulation.
Study burden and risks
There is a risk of syncope during the HUT procedure. The participant will be
tilted back to supine position should any pre-syncope symptoms occur. The MRI
scans of the brain will be reviews by a radiologist for unexpected findings,
which could be a burden. The participants have no personal benefits to taking
part, but the data will aid our understanding of the brain involvement in DMD
and help improve clinical care.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
* Age over 10 years (DMD) or 12 years (healthy)
* Male
* Ambulant
For patients only:
- a mutation in the DMD gene that affects both Dp427 and Dp140
Exclusion criteria
* No informed consent
* Medical history of CV disease, diabetes mellitus, neurological disease (other
than DMD)
* History of recurrent syncope
* Joint contractures preventing the use of the HUT
* Contraindication to MRI exposure (*vragenlijst MRI onderzoek*)
* Inability to lie supine for at least 45 minutes
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | NL58182.058.16 |