To evaluate Hex4 concentrations in CSF from patients with infantile-onset (IOPD) and late-onset (LOPD) Pompe disease
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective:
To evaluate Hex4 concentrations in CSF from patients with infantile-onset
(IOPD) and late-onset (LOPD) Pompe disease
Endpoint:
Concentration of Hex4 in CSF of patients with IOPD and LOPD
Secondary outcome
Secondary objectives:
-To evaluate Hex4 concentrations in plasma and urine of patients with IOPD and
LOPD
-To evaluate inflammatory biomarkers, including NfL, in CSF, and concomitantly
in plasma and/or serum, of patients with IOPD and LOPD
Endpoints:
-Concentration of Hex4 in plasma and of creatinine normalized Hex4 in urine,
concomitantly drawn at the time of CSF collection, of patients with IOPD and
LOPD
-Concentration of biomarkers, including NfL, in CSF, plasma and/or serum from
patients with IOPD and LOPD
Background summary
Pompe disease is a rare neuromuscular disorder caused by a genetic deficiency
of acid alpha-glucosidase (GAA) that results in lysosomal accumulation of
glycogen and subsequent neuromuscular pathology (1). Current standard of care
enzyme replacement therapies (ERT) do
not treat central nervous system (CNS) involvement (2, 3, 4, 5). An
understanding of CNS pathogenesis and disease progression is critical in these
patients. Hexose tetrasaccharide (Hex4), a biomarker reflective of glycogen
accumulation, used clinically for diagnosis (6, 7), is potentially
useful as a biomarker of CNS disease. Although CSF Hex4 is elevated in an
animal model of Pompe disease (JCR Pharmaceuticals, World Symposium 2021;
unpublished Sponsor data), no data are available regarding this biomarker in
CSF of patients with Pompe disease. The primary
goal of this study is to understand whether CSF Hex4 and other inflammatory
biomarkers, including neurofilament light chain (NfL), are elevated in patients
with Pompe disease and could be further evaluated in clinical trials to monitor
CNS glycogen accumulation.
Study objective
To evaluate Hex4 concentrations in CSF from patients with infantile-onset
(IOPD) and late-onset (LOPD) Pompe disease
Study design
Multi-center, non-randomized
Intervention
not applicable
Study burden and risks
Patients will perform 2 visits of a maximum duration of 2 hours per visit: a
screening visit during which the informed consent will be discussed and the
second visit to undergo the planned procedure including study procedures. The
procedures for this study are a single venipuncture, onetime urine collection,
and a single lumbar puncture. Patients with Pompe disease who have to undergo a
procedure for which they are sedated as part of their standard of care or
treatment will be asked to participate in the study. In this way there is no
extra sedation moments for the patients. IOPD patients annually undergo an MRI
under sedation (these young patients otherwise cannot lie still for long
enough), LOPD patients occasionally have a malfunctioning venous port, which is
replaced under sedation.
Risks related to lumbar punctures and venipunctures (the actual study
procedures):
Lumbar puncture: there may be some local pain and the puncture may cause
bruising (bruising) or bleeding. There may be post-punctual headache, infection
(meningitis or epidural abscess), spinal hematoma, nerve root damage, or
cerebral hernia.
Venipuncture: this may be a little painful and the puncture may cause a bruise.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
I 01. Participants who have a confirmed diagnosis of LOPD and clinical signs or
symptoms OR
participants who have a confirmed diagnosis of IOPD.
I 02. Capable of giving signed informed consent as described in Appendix 1
(Section 10.1) of
the protocol which includes compliance with the requirements and restrictions
listed in the
informed consent form (ICF) and in this protocol; OR If participant is <18
years old,
parent(s) or legally authorized representative(s) (LAR) must be capable of
giving signed
informed consent as described in Appendix 1 (Section 10.1) which includes
compliance
with the requirements and restrictions listed in the ICF and in this protocol.
Exclusion criteria
E 01. Chronic illness, except for LOPD, IOPD, or directly resulting from Pompe
disease, that, at
the discretion of the Investigator, could have an impact on Hex4 and
inflammatory markers in the CSF.
E 02. Any acute illness that, at the discretion of the Investigator, could have
an impact on Hex4
and inflammatory markers in the CSF.
E 03. High risk of complications from lumbar puncture or potentially associated
procedural
sedation, as judged by the Investigator.
E 04. Concurrent treatment with any experimental drug or experimental vaccine.
E 05. Participation in another clinical trial with any investigational drug
within 30 days or 5 half-lives, whichever is greater, prior to study start (Day
1).
E 06. Previous participation in any clinical trial involving gene therapy.
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 | NL83999.000.23 |