Status:

COMPLETED

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

Lead Sponsor:

University of Pennsylvania

Collaborating Sponsors:

National Institute of Neurological Disorders and Stroke (NINDS)

Conditions:

Cognition Disorder

Attention Deficit Disorder

Eligibility:

All Genders

18-55 years

Phase:

PHASE2

Brief 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 fun...

Detailed Description

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 fun...

Eligibility Criteria

Inclusion

  • INCLUSION:
  • To be included in the protocol, study participants must meet the following criteria:
  • Age 18 - 55 years, inclusive
  • A history of having sustained a moderate or severe TBI \>= 6 months prior to enrollment. Evidence will be any one of the following 3 criteria:
  • GCS 3 - 12 (GCS obtained in Emergency Room and noted in medical record)
  • Post-traumatic amnesia \> 24 hours
  • TBI-related abnormality on neuroimaging (either CT or MRI). (Some missing information about the initial injury (i.e., documentation of initial GCS) is not necessarily exclusionary if the bulk of the available history indicates that the patient suffered a TBI and meets the inclusion criteria)
  • Persistent post-concussive symptoms, according to the DSM-IV Research Criteria for
  • Post-Concussional Disorder, including:
  • a) Difficulty in attention or memory. b) One or more of the following symptoms, which started shortly after the trauma and persist for at least three months: i) Fatigability ii) Disordered sleep iii) Changes in personality iv) Apathy or lack of spontaneity c) Symptoms in criteria (a) and (b) must have their onset after trauma, or there was a significant worsening of pre-existing symptoms after trauma.
  • d) Disturbance from these symptoms causes significant impairment of social or occupational functioning and represents a significant decline from previous level of functioning.
  • Ability to read, write, and speak English
  • Ability to give informed consent.
  • EXCLUSION:
  • Evidence of penetrating brain injury.
  • Contraindication to methylphenidate therapy:
  • Known glaucoma (consistently raised intraocular pressure with or without associated optic nerve damage)
  • 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)
  • Known hypersensitivity to methylphenidate (hives, difficulty breathing, and swelling of face, lips, tongue, or throat).
  • Known severe anxiety or restlessness which prevents from doing day to day activities.
  • Known preexisting hypertension, heart failure, myocardial infarction, or ventricular arrhythmia.
  • Known preexisting psychosis, bipolar illness.
  • History of seizures, or interictal epileptiform discharges (IEDs) on EEG in absence of seizures.
  • Known peripheral vasculopathy, including Raynaud s phenomenon.
  • History of drug dependence or alcoholism.
  • Concomitant treatment with coumadin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and tricyclic drugs (e.g., imipramine,clomipramine, desipramine).
  • Concomitant therapy with monoamine oxidase inhibitors (such as Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine)
  • Concomitant treatment with blood pressure medication (both for high and low blood pressure).
  • Pregnancy
  • Breastfeeding
  • History or evidence of disabling pre-existing or co-existing disabling neurologic or psychiatric disorders not related to TBI, such as:
  • Multiple sclerosis, pre- or co-existing
  • Stroke (other than stroke at the time of TBI)
  • Pre-existing disabling developmental disorder
  • Pre-existing epilepsy
  • Pre-existing major depressive disorder, aggressive behavior, hostility
  • Pre-existing schizophrenia
  • Contraindication to MRI scanning
  • Ferromagnetic metal in the cranial cavity or eye, e.g., aneurysm clip, implanted neural stimulator, cochlear implant, or ocular foreign body
  • Implanted cardiac pacemaker or auto-defibrillator or pump
  • Non-removable body piercing
  • Claustrophobia
  • Inability to lie supine for two hours
  • Contraindication to TMS, such as metal in the cranial cavity or implanted electronic hardware.
  • Current participation in other interventional clinical trial
  • 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.
  • Present history of alcohol and substance abuse disorder determined (by DSM-IV).
  • Body mass index (BMI) \> 40

Exclusion

    Key Trial Info

    Start Date :

    August 6 2014

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    June 21 2017

    Estimated Enrollment :

    11 Patients enrolled

    Trial Details

    Trial ID

    NCT02225106

    Start Date

    August 6 2014

    End Date

    June 21 2017

    Last Update

    November 15 2019

    Active Locations (1)

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    1

    National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, United States, 20892