Effects of Huperzine A in Treatment of Moderate to Severe TBI
Verified March 2015 by Spaulding Rehabilitation Hospital
Information provided by (Responsible Party):
Ross D. Zafonte, MD, Spaulding Rehabilitation Hospital
First received: August 28, 2012
Last updated: March 24, 2015
Last verified: March 2015
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.
Traumatic Brain Injury
Drug: Huperzine A
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
||Huperzine A for the Treatment of Cognitive, Mood, and Functional Deficits After Moderate and Severe TBI
Primary Outcome Measures:
- Change in Cognition (learning and memory)from baseline [ Time Frame: Measured for approximately one year ] [ Designated as safety issue: No ]
To determine whether Huperzine A, as compared to placebo, has a differential effect on learning and memory functions after moderate to severe TBI, as measured by the California Verbal Learning Test- II (CVLT-II). This CVLT-II will be measured at baseline, 6 weeks, 12 weeks and at 52 weeks.
Secondary Outcome Measures:
- Changes in neurophysiological markers (EEG and TMS)from baseline [ Time Frame: Measured for approximately one year ] [ Designated as safety issue: No ]
To determine whether administration of Huperzine A produces significant differences in neurophysiologic markers (as indexed by EEG event related potentials (P50 and P300) and TMS-indexed cortical excitability (cholinergic activity)) associated with cognition relative to a placebo. This will be measured at baseline, 6 weeks, 12 weeks, 24 weeks and 52 weeks.
- Changes in seizure activity from baseline [ Time Frame: Measured for approximately 12 weeks ] [ Designated as safety issue: No ]
To determine whether Huperzine A reduces the prevalence/frequency of post-traumatic seizures after moderate and severe TBI as compared to placebo at 12 weeks post-enrollment (immediate seizures prevalence). Seizures will be continually monitored through the study.
- Safety of Huperzine-A [ Time Frame: Measured for approximately one year ] [ Designated as safety issue: Yes ]
To evaluate the safety and tolerability of Huperzine A in this patient population as compared to placebo. Safety and tolerability will be assessed by a comparison of the frequency and intensity of adverse effects, as measured throughout the study participation.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2015 (Final data collection date for primary outcome measure)
Experimental: Huperzine A
Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A.
Drug: Huperzine A
Huperzine A will be administered for 12 weeks as outlined in the Arm Description
- huperzia serrata
- chinese club moss
Placebo Comparator: Placebo
Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A).
|Ages Eligible for Study:
||18 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01676311
|Spaulding Rehabilitation Hospital
|Charlestown, Massachusetts, United States, 02129 |
Spaulding Rehabilitation Hospital
||Ross Zafonte, DO
||Spaulding Rehabilitation Hospital
No publications provided
||Ross D. Zafonte, MD, Principal Investigator, Spaulding Rehabilitation Hospital
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 28, 2012
||March 24, 2015
||United States: Food and Drug Administration
United States: Institutional Review Board
Keywords provided by Spaulding Rehabilitation Hospital:
transcranial magnetic stimulation
chinese club moss
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 26, 2015
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs