Recruitment

Recruitment Status
Terminated
Estimated Enrollment
30

Inclusion Criteria

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

Exclusion Criteria

Evidence of penetrating brain injury.
Stroke (other than stroke at the time of TBI)
History of drug dependence or alcoholism.
...
Evidence of penetrating brain injury.
Stroke (other than stroke at the time of TBI)
History of drug dependence or alcoholism.
Present history of alcohol and substance abuse disorder determined by DSM-IV
Inability to lie supine for two hours
History of seizures, or interictal epileptiform discharges (IEDs) on EEG in absence of seizures.
Pre-existing epilepsy
Pregnancy
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.
Non-removable body piercing
Implanted cardiac pacemaker or auto-defibrillator or pump
Body mass index (BMI) > 30
Known hypersensitivity to methylphenidate (hives, difficulty breathing, and swelling of face, lips, tongue, or throat).
Multiple sclerosis, pre- or co-existing
Claustrophobia
Known severe anxiety or restlessness which prevents from doing day to day activities.
Pre-existing major depressive disorder, aggressive behavior, hostility
Contraindication to TMS, such as metal in the cranial cavity or implanted electronic hardware.
Known glaucoma (consistently raised intraocular pressure with or without associated optic nerve damage)
Concomitant treatment with blood pressure medication (both for high and low blood pressure).
Pre-existing schizophrenia
Known preexisting hypertension, heart failure, myocardial infarction, or ventricular arrhythmia.
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)
Ferromagnetic metal in the cranial cavity or eye, e.g., aneurysm clip, implanted neural stimulator, cochlear implant, or ocular foreign body
Concomitant therapy with monoamine oxidase inhibitors (such as Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine))
Pre-existing disabling developmental disorder
Concomitant treatment with coumadin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine).
Known preexisting psychosis, bipolar illness.
Current participation in other interventional clinical trial
Breastfeeding
Known peripheral vasculopathy, including Raynaud's phenomenon.

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

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

Exclusion Criteria

Evidence of penetrating brain injury.
Stroke (other than stroke at the time of TBI)
History of drug dependence or alcoholism.
...
Evidence of penetrating brain injury.
Stroke (other than stroke at the time of TBI)
History of drug dependence or alcoholism.
Present history of alcohol and substance abuse disorder determined by DSM-IV
Inability to lie supine for two hours
History of seizures, or interictal epileptiform discharges (IEDs) on EEG in absence of seizures.
Pre-existing epilepsy
Pregnancy
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.
Non-removable body piercing
Implanted cardiac pacemaker or auto-defibrillator or pump
Body mass index (BMI) > 30
Known hypersensitivity to methylphenidate (hives, difficulty breathing, and swelling of face, lips, tongue, or throat).
Multiple sclerosis, pre- or co-existing
Claustrophobia
Known severe anxiety or restlessness which prevents from doing day to day activities.
Pre-existing major depressive disorder, aggressive behavior, hostility
Contraindication to TMS, such as metal in the cranial cavity or implanted electronic hardware.
Known glaucoma (consistently raised intraocular pressure with or without associated optic nerve damage)
Concomitant treatment with blood pressure medication (both for high and low blood pressure).
Pre-existing schizophrenia
Known preexisting hypertension, heart failure, myocardial infarction, or ventricular arrhythmia.
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)
Ferromagnetic metal in the cranial cavity or eye, e.g., aneurysm clip, implanted neural stimulator, cochlear implant, or ocular foreign body
Concomitant therapy with monoamine oxidase inhibitors (such as Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine))
Pre-existing disabling developmental disorder
Concomitant treatment with coumadin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine, clomipramine, desipramine).
Known preexisting psychosis, bipolar illness.
Current participation in other interventional clinical trial
Breastfeeding
Known peripheral vasculopathy, including Raynaud's phenomenon.

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)