Effects of Huperzine A in Treatment of Moderate to Severe TBI
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Intervention: Huperzine A; Placebo
Intervention description: Huperzine A will be administered for 12 weeks as outlined in the Arm Description; Placebo Arm (blinded randomization) for Huperzine A Intervention
Intervention MeSH terms: Huperzine A
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: cognition; seizures; electroencephalography; transcranial magnetic stimulation; huperzine; chinese club moss

Summary:

      We will explore the use of Huperzine A in patients who have sustained a moderate to severe
      Traumatic Brain Injury. We aim to determine whether Huperzine A, as compared with placebo,
      would have an effect on memory function after TBI. Additionally, we aim to determine whether
      use of Huperzine A in these patients can change brain activity (as indexed by EEG and
      Transcranial Magnetic Stimulation - TMS), and reduce prevalence/frequency of post-traumatic
      seizures. We also aim to evaluate the safety of Huperzine A in this population as compared
      with placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females aged 18 to 65

          -  Moderate or severe TBI, based on admission Emergency Room GCS 3-12

          -  All subjects will be greater than 2 weeks, but no more than 1 year, after the
             qualifying TBI, and will be symptomatic at enrollment (i.e. all subjects will exhibit
             evidence of ongoing posttraumatic amnesia via the Galveston Orientation Amnesia test
             (GOAT), or score at least 1.5 SD below the mean for completion time on Part B of the
             Trail Making Test.

          -  Agreement to undergo no changes in concomitant medications (including dietary
             supplements) or therapeutic interventions during the first 12 weeks of the study (that
             is, the 12 weeks of dosing with study drug), except where medically indicated. Stable
             concomitant drug regimen (greater than two weeks pre-enrollment without changes)

          -  Normal swallowing

          -  English-speaking (since not all of the outcome metrics are normed outside of the
             English language)

          -  Patient can be on seizure medication.

        Exclusion Criteria:

          -  Patients taking acetylcholinesterase inhibitors and other cholinergic and
             anticholinergic drugs (e.g., tacrine, physostigmine, velnacrine, donepezil,
             rivastigmine, metrifonate) and CYP1A inducing drugs.

          -  Evidence of more than 1 seizure in the past 4 weeks prior to enrollment: Patients may
             not be enrolled if there is evidence of more than one seizure (clinical or
             electrographic, but not including epileptiform or other irritative discharges) during
             the 4 weeks prior to enrollment.

          -  Premorbid history of epilepsy with seizure frequency >1 per month: Patients with a
             history of idiopathic epilepsy may not be enrolled if their seizure frequency was > 1
             per month in the 3 months prior to injury. If pre-injury seizure frequency was < 1 per
             month but there is documented evidence that post-injury seizure frequency is > 1 per
             month or there is documented evidence of an increase in the severity or duration of a
             single seizure relative to the premorbid history, the patient must be excluded.

          -  Evidence of premorbid major CNS disorder, developmental disorder, psychiatric disorder
             or substance abuse: Prior to sustaining TBI, patient was diagnosed and/or treated for
             a major neurologic condition, pervasive developmental disorder (e.g., mental
             retardation, autism), psychiatric disorder or substance abuse that continued to
             produce functional disability up to the time of injury.

          -  Individuals with disorders of consciousness, as defined at the time of screening of
             having vegetative and/or minimally conscious state, will not be enrolled. However,
             these patients may be followed until they:

               -  Meet eligibility criteria

               -  Are more than 12 weeks post injury

               -  Are discharged

          -  Pregnancy, as determined by urine hCG testing before randomization

          -  Breast feeding females

          -  Significant hematologic, renal or hepatic dysfunction [Hepatic/renal dysfunction is
             generally identified as lab results > two times the upper limits of normal (ULN), and
             hematologic dysfunction is determined by clinically significant abnormal lab results],
             on baseline laboratory examination.

          -  Slow heart rate (bradycardia) or other heart conditions related to rate

          -  History of peptic ulcer disease

          -  History of asthma or emphysema

          -  History of GI/urinary tract blockages (i.e. ileus, IBS)

          -  History of glaucoma