Effects of Huperzine A in Treatment of Moderate to Severe TBI

NCT ID: NCT01676311

Last Updated: 2019-11-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2018-08-31

Brief 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.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Huperzine A

Intervention Type: DRUG

Huperzine A will be administered for 12 weeks as outlined in the Arm Description

Placebo

Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo Arm (blinded randomization) for Huperzine A Intervention

Interventions

Huperzine A

Huperzine A will be administered for 12 weeks as outlined in the Arm Description

Intervention Type: DRUG

Placebo

Placebo Arm (blinded randomization) for Huperzine A Intervention

Intervention Type: DRUG

Other Intervention Names

huperzia serrata; chinese club moss

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spaulding Rehabilitation Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ross D. Zafonte, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ross Zafonte, DO

Role: PRINCIPAL_INVESTIGATOR

Spaulding Rehabilitation Hospital

Locations

Spaulding Rehabilitation Hospital

Charlestown, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2012-p-002490

Identifier Type: -

Identifier Source: org_study_id