Recruitment

Recruitment Status
Terminated
Estimated Enrollment
30

Inclusion Criteria

Disturbance from these symptoms causes significant impairment of social or occupational functioning and represents a significant decline from previous level of functioning.
Disordered sleep
Fatigability
...
Disturbance from these symptoms causes significant impairment of social or occupational functioning and represents a significant decline from previous level of functioning.
Disordered sleep
Fatigability
Ability to give informed consent.
Symptoms in criteria (a) and (b) must have their onset after trauma, or there was a significant worsening of pre-existing symptoms after trauma.
Ability to read, write, and speak English
Age 18 - 55 years, inclusive
Post-traumatic amnesia > 24 hours
Difficulty in attention or memory.
Apathy or lack of spontaneity
TBI-related abnormality on neuroimaging (either CT or MRI).
Changes in personality
GCS 3 - 12 (GCS obtained in Emergency Room and noted in medical record)

Exclusion Criteria

Breastfeeding
Pre-existing major depressive disorder, aggressive behavior, hostility
Concomitant treatment with blood pressure medication (both for high and low blood pressure).
...
Breastfeeding
Pre-existing major depressive disorder, aggressive behavior, hostility
Concomitant treatment with blood pressure medication (both for high and low blood pressure).
Concomitant therapy with monoamine oxidase inhibitors (such as Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine))
Implanted cardiac pacemaker or auto-defibrillator or pump
Motor tics or a family history of Tourette's syndrome (diagnosed by presence of both multiple motor and one or more vocal tics over the period of a year, with no more than three consecutive tic-free months)
Concomitant treatment with coumadin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine).
Claustrophobia
History of drug dependence or alcoholism.
Pregnancy
Known peripheral vasculopathy, including Raynaud's phenomenon.
Known severe anxiety or restlessness which prevents from doing day to day activities.
Present history of alcohol and substance abuse disorder determined by DSM-IV
Non-adherence to use of effective method of contraception for females of able to become pregnant for time from enrollment to the study until 2 weeks after completion of the study drug.
Pre-existing schizophrenia
Body mass index (BMI) > 30
Current participation in other interventional clinical trial
Known preexisting psychosis, bipolar illness.
Pre-existing epilepsy
Evidence of penetrating brain injury.
Known preexisting hypertension, heart failure, myocardial infarction, or ventricular arrhythmia.
Inability to lie supine for two hours
Known glaucoma (consistently raised intraocular pressure with or without associated optic nerve damage)
Ferromagnetic metal in the cranial cavity or eye, e.g., aneurysm clip, implanted neural stimulator, cochlear implant, or ocular foreign body
History of seizures, or interictal epileptiform discharges (IEDs) on EEG in absence of seizures.
Non-removable body piercing
Known hypersensitivity to methylphenidate (hives, difficulty breathing, and swelling of face, lips, tongue, or throat).
Pre-existing disabling developmental disorder
Multiple sclerosis, pre- or co-existing
Contraindication to TMS, such as metal in the cranial cavity or implanted electronic hardware.
Stroke (other than stroke at the time of TBI)

Summary

Conditions
Traumatic Brain Injury
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 55 years
Gender
Both males and females

Description

Males and females (n=30), between the ages of 18 and 55 years in the chronic stage after TBI who experience deficits in neuropsychological function from TBIs incurred 6 months after the injury, will be recruited from military treatment facilities or civilian clinics when presenting for clinical mana...

Males and females (n=30), between the ages of 18 and 55 years in the chronic stage after TBI who experience deficits in neuropsychological function from TBIs incurred 6 months after the injury, will be recruited from military treatment facilities or civilian clinics when presenting for clinical management of TBI or post-concussive symptoms. 1. Study participants will be evaluated using brain MRI, psychometric measures adapted from the TBI Common Data Elements, attention tests and information about details of the injury and experience of post-concussive symptoms will be recorded. Transcranial magnetic stimulation (TMS) with placebo and with methylphenidate (60 mg by mouth) challenge will be performed to predict a stimulant response. 2. Subjects will be studied with [11C]-raclopride PET in two imaging sessions. One session will be after administration of placebo and the other after methylphenidate, 60 mg by mouth. Both placebo and methylphenidate will be given 60 minutes prior to injection of [11C]-raclopride to allow for peak uptake of methylphenidate in the brain. The binding potential of [11C]-raclopride relative to a non-displaceable reference region (cerebellum), BPND, will be used as a measure of D2/D3 receptor availability. The difference in BPND between methylphenidate and placebo (ΔBPND) is used to measure of tonic DA release. 3. Subjects will then be treated with oral methylphenidate, using a forced titration up to a dose of 30 mg given twice daily for 4 weeks. At that point, the neuropsychologic tests are repeated. Outcome measures: The primary outcome is change in information processing speed during neuropsychologic testing.

Inclusion Criteria

Disturbance from these symptoms causes significant impairment of social or occupational functioning and represents a significant decline from previous level of functioning.
Disordered sleep
Fatigability
...
Disturbance from these symptoms causes significant impairment of social or occupational functioning and represents a significant decline from previous level of functioning.
Disordered sleep
Fatigability
Ability to give informed consent.
Symptoms in criteria (a) and (b) must have their onset after trauma, or there was a significant worsening of pre-existing symptoms after trauma.
Ability to read, write, and speak English
Age 18 - 55 years, inclusive
Post-traumatic amnesia > 24 hours
Difficulty in attention or memory.
Apathy or lack of spontaneity
TBI-related abnormality on neuroimaging (either CT or MRI).
Changes in personality
GCS 3 - 12 (GCS obtained in Emergency Room and noted in medical record)

Exclusion Criteria

Breastfeeding
Pre-existing major depressive disorder, aggressive behavior, hostility
Concomitant treatment with blood pressure medication (both for high and low blood pressure).
...
Breastfeeding
Pre-existing major depressive disorder, aggressive behavior, hostility
Concomitant treatment with blood pressure medication (both for high and low blood pressure).
Concomitant therapy with monoamine oxidase inhibitors (such as Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine))
Implanted cardiac pacemaker or auto-defibrillator or pump
Motor tics or a family history of Tourette's syndrome (diagnosed by presence of both multiple motor and one or more vocal tics over the period of a year, with no more than three consecutive tic-free months)
Concomitant treatment with coumadin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine).
Claustrophobia
History of drug dependence or alcoholism.
Pregnancy
Known peripheral vasculopathy, including Raynaud's phenomenon.
Known severe anxiety or restlessness which prevents from doing day to day activities.
Present history of alcohol and substance abuse disorder determined by DSM-IV
Non-adherence to use of effective method of contraception for females of able to become pregnant for time from enrollment to the study until 2 weeks after completion of the study drug.
Pre-existing schizophrenia
Body mass index (BMI) > 30
Current participation in other interventional clinical trial
Known preexisting psychosis, bipolar illness.
Pre-existing epilepsy
Evidence of penetrating brain injury.
Known preexisting hypertension, heart failure, myocardial infarction, or ventricular arrhythmia.
Inability to lie supine for two hours
Known glaucoma (consistently raised intraocular pressure with or without associated optic nerve damage)
Ferromagnetic metal in the cranial cavity or eye, e.g., aneurysm clip, implanted neural stimulator, cochlear implant, or ocular foreign body
History of seizures, or interictal epileptiform discharges (IEDs) on EEG in absence of seizures.
Non-removable body piercing
Known hypersensitivity to methylphenidate (hives, difficulty breathing, and swelling of face, lips, tongue, or throat).
Pre-existing disabling developmental disorder
Multiple sclerosis, pre- or co-existing
Contraindication to TMS, such as metal in the cranial cavity or implanted electronic hardware.
Stroke (other than stroke at the time of TBI)

Locations

Bethesda, Maryland, 20814
Bethesda, Maryland, 20814

Tracking Information

NCT #
NCT02148783
Collaborators
National Institutes of Health (NIH)
Investigators
  • Study Director: Ramon R Diaz-Arrastia, MD, PhD Uniformed Services University / NINDS Principal Investigator: Eric Wassermann, MD National Institute of Neurological Disorders and Stroke (NINDS)
  • Study Director: Ramon R Diaz-Arrastia, MD, PhD Uniformed Services University / NINDS Eric Wassermann, MD National Institute of Neurological Disorders and Stroke (NINDS)