Dopamine Receptor Imaging to Predict Response to Stimulant Therapy in Chronic TBI

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.

Conditions

• Traumatic Brain Injury

Interventions

DRUG

methylphenidate

This is an open-labeled 4 week methylphenidate administration, 30 mg twice daily by mouth. Placebo and methylphenidate will also be administered as a single dose before one of the two PET and TMS sessions, in a single blinded manner (the participant will not know whether active drug or placebo was administered). PET imaging with \[11C\]-raclopride, a D2/D3 receptor ligand will be performed after administration of placebo or oral methylphenidate to measure endogenous DA release in TBI patients. Structural MRI will be performed before methylphenidate administration. TMS after placebo or methylphenidate will be performed to measure intracortical inhibition and dopaminergic activity.

DRUG

Placebo

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• Uniformed Services University of the Health Sciences

  lead FED

Principal Investigators

• Ramon R Diaz-Arrastia, MD, PhD · Uniformed Services University / NINDS

• Eric Wassermann, MD · National Institute of Neurological Disorders and Stroke (NINDS)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-09-30

Primary Completion

2018-08-31

Completion

2018-08-31

Countries

• United States

Study Locations