The primary objective is to study if quantitative (3- and 7-Tesla) MRI protocols (MRI perfusion, diffusion tensor imaging (DTI), and chemical shift imaging (CSI)) are able to detect phenotype conversion earlier than conventional MRI. Results will be…
ID
Source
Brief title
Condition
- Neurological disorders congenital
- Congenital and peripartum neurological conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is conversion to cerebral ALD.
Secondary outcome
Natural history of X-ALD.
Background summary
Patients with X-linked adrenoleukodystrophy (X-ALD) develop adrenocortical
insufficiency (80% during childhood) and a progressive myelopathy (in
adulthood). In most patients (sub)clinical hypogonadism is present. Many (40%
before the age of 18 years) develop rapidly progressive cerebral demyelination
(cerebral ALD; cALD). cALD can be treated with haematopoetic cell
transplantation (HCT) in early stage disease. To detect cALD in an early
pre-symptomatic stage children with X-ALD undergo MRI of the brain every 6
months and adults every 12 months. If there were methods to stratify patients
according to risk for cerebral ALD follow-up could be individualized and
unnecessary examinations reduced.
Recently the Spinoza Centre, a new research facility for MRI neuroimaging
research at high field strength (7-Tesla) was established. This offers the
possibility to implement groundbreaking novel MRI imaging techniques in the
care for X-ALD patients. Acquiring data at a field strength of 7-Tesla enables
measuring at unprecedented level of detail, with a spatial resolution of 0.5
mm. I aim to perform additional MRI sequences at 7-Tesla, parallel to the
prospective cohort study, to evaluate if quantitative MRI protocols (MRI
perfusion, DTI and CSI) are able to detect phenotype conversion earlier than
3-Tesla imaging techniques.
To gain power for quantitative MRI sequences on both 3- and 7- Tesla I will
recruit healthy-age matched-volunteers to participate in this study.
Study objective
The primary objective is to study if quantitative (3- and 7-Tesla) MRI
protocols (MRI perfusion, diffusion tensor imaging (DTI), and chemical shift
imaging (CSI)) are able to detect phenotype conversion earlier than
conventional MRI. Results will be correlated to MRI images of healthy age
matched controls. We will also search for new prognostic biomarkers with
lipidomics analysis in plasma and cytokine profiles in CSF (optional). We will
quantify quality of life, disability and signs of hypogonidsm.
The secondary objective is to validate known genetic biomarkers for the
occurrence of cerebral ALD.
Study design
The study is a longitudinal cohort study for a period of 3 years, with visits
to the hospital every 6 or 12 months (depending on age). Healthy volunteers
will visit the AMC once.
Study burden and risks
Currently, patients with X-linked adrenoleukodystrophy visit the hospital at
least once a year for neurological examination, a MRI scan of the brain and
endocrinological tests. The frequency of hospital visits will not change, the
only differences are:
- Longer neurological history and examination, with questionnaires and scales
(SF-36, ALDS, CIS, ICIQ, SSPROM, mJOA, 6MWT, Timed Up and Go test, MMSE)
- Longer MRI protocol (70 minutes versus 45 minutes)
- Extra laboratory tests (additional blood for lipidomics analysis, isolation
of extracellular vesicles, DNA storage)
- Lumbar punction (optional)
- Single measurement of testicular volume by ultrasound (optional)
Healthy volunteers will visit the AMC once for:
- Screening for neurological disease and/or cardiovascular risk factors
(Structured history and physical examination)
- 3-Tesla MRI protocol (quantitative DTI, MRS/CSI, ASL) for controls between 12
and 18 years and for controls aged 18 years or older, including intravenous
gadolinium for controles aged 18 years or older and/or
- 7-Tesla MRI protocol (quantitative DTI, MRS/CSI), solely for controles aged
18 years or older.
Meibergdreef 9
Amsterdam 1019TH
NL
Meibergdreef 9
Amsterdam 1019TH
NL
Listed location countries
Age
Inclusion criteria
Patients:
- male patients with X-ALD (confirmed by ABCD1 mutation analysis)
- age for which follow-up is normally recommended (2 years and older)
- willing to undergo regular follow-up visits (twice yearly if < 12 years and yearly if > 12 years) with blood sampling and MRI scan of the brain.
- Informed consent obtained from participant or legal guardian in case of a minor;For the additional MRI sequences at 7-Tesla participants must meet these additional criteria:
- Age 18 years or older
- Supplementary informed consent procedure;Subjects eligible to participate as healthy controls must meet all of the following criteria:
- Willing to visit the hospital
- 12 years or older
- For administration of gadolinium: age 18 years or older
- Informed consent obtained from participant
- Informed consent obtained from participant or legal guardian in case of a minor
Exclusion criteria
Patients:
- unable to visit the hospital for follow-up (for instance, due to advanced disease)
- co-existing neurological disease making interpretation of acquired data difficult (for instance, multiple sclerosis);A potential healthy control who meets any of the following criteria will be excluded from participation in this study:
- neurological disease (because this would impede accurate interpretation of the MRI imaging data)
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 | NL51345.018.14 |