Recruitment

Recruitment Status
Terminated
Estimated Enrollment
30

Inclusion Criteria

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

Exclusion Criteria

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

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

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

Exclusion Criteria

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

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)
About Us
Innovation
Privacy
Terms
Copyright
Get Well Soon © Copyright 2024