Effects of Huperzine A in Treatment of Moderate to Severe TBI

NCT01676311 | Terminated Phase 2 Results DMC

• 1 other identifier: 2012-p-002490
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Keywords

cognition; seizures; electroencephalography; transcranial magnetic stimulation; huperzine; chinese club moss

Outcome Measures

Primary Outcomes (1)

• California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory

  Measure of learning and memory function. Three indices of the CVLT-II were calculated. The full name, abbreviated name, and the minimum and maximum possible scores of each index are indicated below: 1. California Verbal Learning Test- 2nd Edition- Total Learning \[CVLT-II-TL\] (Minimum score=0; Maximum score= 80) 2. California Verbal Learning Test- 2nd Edition- Short delay free recall \[CVLT-II-SDFR\] (Minimum score=0; Maximum score=16) 3. California Verbal Learning Test- 2nd Edition- Long delay free recall \[CVLT-II-LDFR\] (Minimum score=0; Maximum score=16) High scores are indicative of greater memory and learning for each index (i.e. better outcome).

  Baseline, 6 weeks, 12 weeks, 24 weeks and at 52 weeks.

Secondary Outcomes (4)

• Amplitude of Event Related Potentials (ERPs) P50 and P300

  Baseline, 12 Weeks

• Latency of Event Related Potentials (ERPs) P50 and P300

  Baseline, 12 weeks

• Number of Participants Who Experienced Post-traumatic Seizure During 12-week Treatment Window

  Baseline and weekly for 12 weeks.

• Number of Participants With Self-reported Side Effects During 12-week Treatment Window

  Baseline and weekly for 12 weeks.

Study Arms (2)

Huperzine A

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Huperzine A DRUG

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

Also known as: huperzia serrata, chinese club moss

Huperzine A

Placebo DRUG

Placebo Arm (blinded randomization) for Huperzine A Intervention

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead

Study Sites (1)

Spaulding Rehabilitation Hospital

Charlestown, Massachusetts, 02129, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Seizures

Interventions

huperzine A

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Enrollment - not able to enroll target N, therefore small number of subjects analyzed. Neurophysiologic measures - difficulty collecting data from subjects for several reasons.

Results Point of Contact

• Title: Ross Zafonte, DO
• Organization: Spaulding Rehabilitation Hospital

rzafonte@mgh.harvard.edu

617-952-5227

Study Officials

• Ross Zafonte, DO

  Spaulding Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 28, 2012
• First Posted: August 30, 2012
• Study Start: December 1, 2013
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: November 5, 2019
• Results First Posted: October 7, 2019

Record last verified: 2019-10

Locations

US (1)