Dopamine Receptor Imaging to Predict Response to Stimulant Therapy in Chronic TBI
Status:
Terminated
Trial end date:
2018-08-01
Target enrollment:
Participant gender:
Summary
Deficits in memory, attention, cognitive, and executive functions are the most common
disabilities after traumatic brain injury (TBI). Dopamine (DA) neurotransmission is
implicated in these neural functions and dopaminergic pathways are recognized to be
frequently disrupted after TBI. One of the most widely used DAergic drugs is methylphenidate
(Ritalin®). Methylphenidate increases synaptic DA levels by binding to presynaptic dopamine
transporters (DAT) and blocking re-uptake. PET with methylphenidate challenge to measure
tonic DA release provides valuable insight into the molecular basis of attention-deficit
hyperactivity disorder (ADHD) and addiction, as well as practical information regarding
likely effectiveness of therapy (1). The objectives of this study are to use PET imaging with
[11C]-raclopride, a D2/D3 receptor ligand, before and after administering methylphenidate, to
measure endogenous DA release in patients who are experiencing problems with cognition,
attention and executive function in the chronic stage after TBI. In addition, we will use TMS
to test short intracortical inhibition, a gamma-aminobutyric acid receptor A (GABAA) -
mediated phenomenon, which is under partial DA control, as a measure of dopaminergic activity
on and off methylphenidate.
Phase:
Phase 2
Details
Lead Sponsor:
Uniformed Services University of the Health Sciences
Collaborator:
National Institutes of Health (NIH)
Treatments:
Central Nervous System Stimulants Dopamine Dopamine Agents Methylphenidate