Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 11:43 PM
Ignite Modification Date:
2025-12-24 @ 11:43 PM
NCT ID:
NCT03221751
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:
NCT03221751
Study Brief:
Protocol Section:
NCT03221751