To determine early and subtle MRI changes in premanifest and early manifest HD patients which distinguish them from the healthy population. This includes both structural/quantitative MRI data and MRI-signs of blood-brain barrier (BBB) breakdown. And…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
- Psychiatric and behavioural symptoms NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- The main study endpoint will be the structural and functional changes of the
premanifest compared to early manifest and healthy family or gene negative
controls, which will be assessed on 7T ultra-high field MR images. We will also
use quantitative MRI approaches, since this enables us to detect small
structural and anatomical differences which cannot be detected on qualitative
MRI acquisitions.
- BBB permeability as determined by DCE-MRI to assess the leakiness of the
cerebral vasculature by dynamically measuring the rate of contrast agent
transfer from blood into the interstitial space (leakage rate; units: ml.min
1.100g). We will compare BBB permeability in early manifest HD with
pre-manifest HD participants.
Secondary outcome
We will assess the relationship between the imaging measures and clinical
scores/ disease burden with regression analysis.
We will investigate if gadolinium, injected during MRI, enters tear fluid.
We will investigate if the level of gadolinium correlates with the level of BBB
leakage on MRI.
Background summary
Accurate estimation of clinical disease onset in Huntington*s Disease (HD)
remains difficult because motor symptoms develop insidiously and may be subtle,
and neuropsychiatric symptoms may precede the onset of motor symptoms by up to
10 years. Reliable biomarkers such as those obtained by ultra-high field
magnetic resonance imaging (MRI) may be useful in determining disease onset and
course and may be used as a diagnostic biomarker for novel treatment therapies.
Furthermore, tear fluid is a source of biomarkers in HD as well. Determining
gadolinium in tears may help to discover early blood-brain barrier (BBB)
breakdown without MRI.
Study objective
To determine early and subtle MRI changes in premanifest and early manifest HD
patients which distinguish them from the healthy population. This includes both
structural/quantitative MRI data and MRI-signs of blood-brain barrier (BBB)
breakdown. And also to lay the foundation for a longitudinal cohort study that
allows to investigate the prognostic implications of these MRI changes.
Furthermore, to investigate if gadolinium, injected during MRI, enters tear
fluid and to investigate if the level of gadolinium correlates with the level
of BBB leakage on MRI.
Study design
This is an observational study in which all participants will be assessed only
once. However, patients will be asked for the consent to be contacted about
follow-up studies.
Study burden and risks
The MRI that will be performed is non-invasive, but in 1:100/1000 subjects,
possible problems can occur on the first contrast solution. Tear fluid
collection is painless and without risks, but may be uncomfortable. The eyes
may feel dry for a few minutes to hours.
P. Debeyelaan 25
Maastricht 6229HX
NL
P. Debeyelaan 25
Maastricht 6229HX
NL
Listed location countries
Age
Inclusion criteria
General inclusion criterium:
- Between 18 years and 75 years of age
Inclusion criteria pre-manifest participants:
- An UHDRS motor score <= 5
- CAG repeat size of 36 or more
*
Inclusion criteria manifest participants:
- An UHDRS motor score > 5
- Disease Stage 1 or 2
- CAG repeat size of 36 or more
- TFC between 7 and 13 (disease stage 1 or 2)
Inclusion Criteria gene negative controls
- a CAG repeat size of 35 or less
Exclusion criteria
- Subjects with contra-indications for a MRI-scan as defined in the MRI
screening form of SCANNEXUS such as claustrophobia, subjects carrying
incompatible metallic devices, subjects who have an allergy for intravenous
contract or subjects who are pregnant.
- Manifest participants who are not capable of consenting
- Manifest patients not capable of undergoing MRI because of involuntary
movements.
- Genotype unknown
- Current participation in a drug trial
- Not agreeing to be informed about incidental findings on the MRI scan
- Known kidney insufficiency
Design
Recruitment
Medical products/devices used
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 | NL79009.068.21 |