Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00220584
Status:
COMPLETED
Last Update Posted:
2012-12-13
First Post:
2005-09-15
Brief Title:
An Open-Label Trial of Donepezil in Fragile X Syndrome
Sponsor:
Stanford University
Organization:
Stanford University
Study Overview
Official Title:
An Open-Label Trial of Donepezil in Fragile X Syndrome
Status:
COMPLETED
Status Verified Date:
2012-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Fragile X syndrome is the most common known inherited cause of neurodevelopmental disability Functional magnetic resonance imaging fMRI studies from our laboratory indicate that specific brain regions using the neurochemical acetylcholine show significantly reduced activation during learning Since donepezil is a medication that enhances acetylcholine function in the brain the purpose of this study is to determine if donepezil has any beneficial effect on behavior or cognition in subjects with fragile X syndrome
Detailed Description:
Fragile X syndrome is the most common genetically inherited cause of neurodevelopmental disability in humans affecting approximately 12000 to 4000 live births Affected individuals have significant long-term problems with learning and often with behavior as well The disorder is caused by the presence of a greatly expanded CGG repeat within the FMR1 gene on the long arm of the X chromosome Abnormal methylation of this repeat and adjacent areas within the FMR1 gene impedes transcription ultimately resulting in reduced production of the FMR1 protein FMRP This protein is expressed in neurons with particularly high levels of gene transcription occurring in the nucleus basalis basal forebrain and hippocampus A recent functional imaging study from our group showed girls with fragile X to have greatly reduced levels of brain activation in the basal forebrain and hippocampal activation during a memory task The nucleus basalis is a cholinergic nucleus with widespread connections to the neocortex It is critical to visuospatial attention in rodents and primates and is presumed to play a similar role in humans The finding of decreased basal forebrain activation in girls with fragile X considered in light of histological evidence showing high transcription levels of FMR1 in healthy nucleus basalis suggests the possibility of a functional cholinergic deficit in fragile X syndrome
Donepezil is an acetylcholinesterase inhibitor which slows the degradation of synaptic acetylcholine thereby increasing its availability It is approved for the treatment of mild-moderate Alzheimers disease It has been studied in several other neurologic disorders--including vascular dementia Lewy Body dementia and Downs syndrome with and without dementia--where it has shown varying degrees of efficacy but consistently high degrees of safety and tolerability The goal of the proposed study is to determine if enhancing cholinergic activity with donepezil has beneficial effects on behavior or cognition in subjects with fragile X syndrome
Donepezil is an acetylcholinesterase inhibitor which slows the degradation of synaptic acetylcholine thereby increasing its availability It is approved for the treatment of mild-moderate Alzheimers disease It has been studied in several other neurologic disorders--including vascular dementia Lewy Body dementia and Downs syndrome with and without dementia--where it has shown varying degrees of efficacy but consistently high degrees of safety and tolerability The goal of the proposed study is to determine if enhancing cholinergic activity with donepezil has beneficial effects on behavior or cognition in subjects with fragile X syndrome
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None