Ignite Creation Date:
2025-12-24 @ 11:43 PM
Ignite Modification Date:
2026-02-21 @ 7:44 PM
Study NCT ID:
NCT03221751
Status:
TERMINATED
Last Update Posted:
2024-02-26
First Post:
2017-07-13
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Prazosin and Cerebrospinal Fluid (CSF) Biomarkers in Mild Traumatic Brain Injury (mTBI)
Sponsor:
VA Office of Research and Development
Organization:
Study Overview
Official Title:
Prazosin and CSF Biomarkers in mTBI
Status:
TERMINATED
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
staffing issues and COVID
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PoND
Brief Summary:
Mild traumatic brain injury (mTBI) from explosions is the "signature injury" of Veterans who have deployed to the wars in Afghanistan and Iraq. Although the immediate effects of a single mTBI usually resolve over days or weeks, multiple mTBIs can lead to both persistent symptoms and, years later, to two fatal progressive brain diseases, chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD). It is believed that CTE and AD are caused by nerve damaging chemicals called tau and beta amyloid produced by the brain but which are not removed from the brain in a normal manner in persons with mTBIs. The investigators will determine in Veterans who experienced mTBIs whether a clinically available drug called prazosin increases removal of tau and beta amyloid from the brain. This will be accomplished by seeing if prazosin reduces the amount of tau and beta amyloid in the spinal fluid that surrounds the brain. If the investigators find such reductions, prazosin will be evaluated as a preventative treatment for CTE and AD in future studies.
Detailed Description:
A majority of neurodegenerative dementing disorders, including Alzheimer's disease, (AD), dementia with Lewy bodies (DLB) and chronic traumatic encephalopathy (CTE), now appear to be caused by the accumulation and aggregation of proteins that cause progressive damage to the brain. Recent preclinical results suggest that clearance of such neurotoxic proteins from the brain may be greatly increased during states where noradrenergic (NA) tone is decreased or blocked, such as anesthesia and normal sleep, but impaired in animal models of mild Traumatic Brain Injury (mTBI). These results also suggest that clearance through this mechanism, which has been termed the 'glymphatic' system, is likely to be decreased in conditions where NA signaling is inappropriately maintained during sleep, such as posttraumatic stress disorder (PTSD). Importantly, the rate at which toxins are cleared through the glymphatic system has been found to be under alpha-1 adrenergic receptor (AR) control, and the application of noradrenergic blockers such as the alpha-1 AR antagonist drug, prazosin, has been shown to increase waking clearance of these proteins to levels normally found during sleep or anesthesia. This suggests two important possibilities: first, that conditions in which the brain NA signaling is increased and sleep is impaired, such as posttraumatic stress disorder (PTSD) and mTBI, may predispose people to decreased clearance of neurotoxic proteins associated with the development and progression of dementia; and second, that the use of prazosin may be able to prevent such effects.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 1I21RX002180-01 | NIH | None | https://reporter.nih.gov/quic… | View |