|- candidate number||21790|
|- NTR Number||NTR5095|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||11-mrt-2015|
|- Secondary IDs||NL49834.068.14 |
|- Public Title||Glutamate and cognition in adults with 22q11DS|
|- Scientific Title||The role of glutamate in cognition in adults with chromosome 22q11 deletion syndrome|
|- hypothesis||It is hypothesize that|
-performance on a cognitive test battery (CANTAB) will be negatively associated with brain glutamate concentrations in adults with 22q11DS
-Cognitive functioning will improve after riluzole administration compared to placebo.
|- Healt Condition(s) or Problem(s) studied||22Q11 deletion syndrome, Cognition|
|- Inclusion criteria||• Confirmed diagnosis of 22q11DS established by FISH, microarray or MLPA analysis. |
•Age 18 and older and mentally competent to give informed consent.
•No psychopharmacological treatment at the time of inclusion
•No presence of a physical/medical condition that may interfere with the study.
•No contraindication for MRI
|- Exclusion criteria||•Other chromosomal abnormalities |
•Current substance abuse / dependence
•Comorbid psychiatric / neurologic disorder
•Contraindications for Riluzole
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-apr-2015|
|- planned closingdate||1-apr-2016|
|- Target number of participants||10|
|- Interventions||On two occasions, non-invasive 7.0 Tesla MRS recordings will be conducted, once following a glutamate challenge (riluzole, 50 mg.) and once following placebo, administered orally.|
|- Primary outcome||The main study parameter will be striatal and ACC glutamate concentrations as measured with H MRS after a glutamate challenge and after placebo.|
|- Secondary outcome||A secondary outcome measure is cognitive functioning, measured with a standardized cognitive battery (CANTAB). A cognitive composite score will be computed using the mean scores of the CANTAB subtests. This score will represent cognitive functioning.|
|- Timepoints||2 weeks|
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES||MSc. Claudia Vingerhoets|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. Therese van Amelsvoort|
|- Sponsor/Initiator ||Maastricht University|
(Source(s) of Monetary or Material Support)
|- Brief summary||22q11 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion on the long arm of chromosome 22. Subjects with this syndrome have an increased risk of developing a variety of psychiatric disorders, particularly schizophrenia and other psychotic disorders. One of the genes located at the deleted region in 22q11DS is known to be involved in glutamatergic neurotransmission. This gene encodes proline dehydrogenase (PRODH), also known as proline oxidase. This enzyme is implicated in converting proline to glutamate. Glutamate, i.e. the major excitatory neurotransmitter in the brain, has been associated with the pathophysiology of psychosis, particularly the cognitive symptoms. Since 22q11DS is associated with progressive cognitive and functional deterioration in combination with psychosis, it could be hypothesized that a neurodegenerative process, as a consequence of chronic high (neurotoxic) concentrations of glutamate could result in neuronal damage. This suggests that abnormal glutamatergic neurotransmission could explain the vulnerability for psychopathology and cognitive decline in 22q11DS.
The main objective of this (pilot) study is to investigate the role of glutamate in cognitive functioning in adults with 22q11DS using a glutamatergic challenge (riluzole )and high-field MRS. We will relate glutamate concentrations in the hippocampus, striatum and anterior cingulate cortex (ACC) with performance on a cognitive test battery (CANTAB).
This study is a double-blind, cross-over placebo controlled (pilot) study. To measure in-vivo glutamate concentrations in the brain, all participants will receive a MRS scan on two occasions, one following placebo and one following a glutamatergic challenge (riluzole, 50 mg.). The order of placebo and drug will be counterbalanced. On both occasions, a cognitive test battery (CANTAB) will be assessed after the MRS scan.
|- Main changes (audit trail)|
|- RECORD||11-mrt-2015 - 25-apr-2015|