Traumatic Brain InjuryPhase 2NCT01676311

Effects of Huperzine A in Treatment of Moderate to Severe TBI

A Phase 2 study testing Huperzine A in people with Traumatic Brain Injury, run by Spaulding Rehabilitation Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Traumatic Brain Injury
What is being tested?: Huperzine A
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 14 participants
Where: 1 siteUnited States
Study dates: Dec 2013to Aug 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 16Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Spaulding Rehabilitation Hospital
Charlestown, Massachusetts, 02129

Other trials in United States

About this study

Official title: Huperzine A for the Treatment of Cognitive, Mood, and Functional Deficits After Moderate and Severe TBI

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
Being tested: Huperzine A, Placebo
Keywords: cognition, seizures, electroencephalography, transcranial magnetic stimulation, huperzine, chinese club moss
Medical subject headings: Brain Injuries, Traumatic, Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Huperzine ADrug
Also called huperzia serrata, chinese club moss
Huperzine A will be administered for 12 weeks as outlined in the Arm Description
PlaceboDrug
Placebo Arm (blinded randomization) for Huperzine A Intervention

Study groups in NCT01676311
Study group	Role	What they receive
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. Receives: Drug: Huperzine A
Placebo	Placebo comparator	Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Baseline, 6 weeks, 12 weeks, 24 weeks and at 52 weeks.

Secondary outcomes (4)

Amplitude of Event Related Potentials (ERPs) P50 and P300
Event Related Potentials (ERPs): P50 and P300 are neurophysiological measurements that index cortical electrical activity associated with a given stimulus. P50 and P300 were measured using auditory stimuli. P50 represents an index of activity in the cholinergic system and has been used to characterize presynaptic cholinergic deficit. P300 is a measure of general cognitive processing elicited during attention, memory, and executive tasks.
Measured: Baseline, 12 Weeks
Latency of Event Related Potentials (ERPs) P50 and P300
Event Related Potentials (ERPs): P50 and P300 are neurophysiological measurements that index cortical electrical activity associated with a given stimulus. P50 and P300 were measured using auditory stimuli. P50 represents an index of activity in the cholinergic system and has been used to characterize presynaptic cholinergic deficit and P300 is a measure of general cognitive processing elicited during attention, memory, and executive tasks.
Measured: Baseline, 12 weeks
Number of Participants Who Experienced Post-traumatic Seizure During 12-week Treatment Window
To determine whether Huperzine A changes the prevalence of post-traumatic seizure after moderate and severe TBI as compared to placebo at 12 weeks post-enrollment (immediate seizures prevalence).
Measured: Baseline and weekly for 12 weeks.
Number of Participants With Self-reported Side Effects During 12-week Treatment Window
To evaluate the safety and tolerability of Huperzine A in this patient population as compared to placebo the frequency of self-reported side effects during the 12-week treatment window were grouped categorically by system (behavioral, cardiac-respiratory, dermatological,gastrointestinal, genitourinary/neurological, hematological, musculoskeletal, neurological).
Measured: Baseline and weekly for 12 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2013Aug 2018

First posted30 Aug 2012 (estimated)
Study startDec 2013
Primary completionAug 2018
Study completionAug 2018

Why it stopped: Insufficient accrual rate: 14 participants enrolled (target of 30).

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01676311
Sponsor's protocol ID: 2012-p-002490
Status last verified: Oct 2019
First submitted: 28 Aug 2012
Last updated: 5 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma

All Traumatic Brain Injury trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Huperzine A for the Treatment of Cognitive, Mood, and Functional Deficits After Moderate and Severe TBI
ClinicalTrials.gov ID: NCT01676311
Acronym / sponsor ID: 2012-p-002490
Conditions: Traumatic Brain Injury
Keywords: cognition, seizures, electroencephalography, transcranial magnetic stimulation, huperzine, chinese club moss
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Insufficient accrual rate: 14 participants enrolled (target of 30).
Enrolment: 14 participants (actual)
Lead sponsor: Spaulding Rehabilitation HospitalUniversity, hospital or other
Study start: Dec 2013 (actual)
Primary completion: Aug 2018 (actual)
Study completion: Aug 2018 (actual)
First posted: 30 Aug 2012 (estimated)
Results: Posted 7 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Huperzine A	Experimental	Drug: Huperzine AHuperzine 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.
Placebo	Placebo comparator	Drug: PlaceboPlacebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A).

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (16 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Huperzine AAlso: huperzia serrata, chinese club mossHuperzine A will be administered for 12 weeks as outlined in the Arm Description	Drug	Huperzine A
PlaceboPlacebo Arm (blinded randomization) for Huperzine A Intervention	Drug	Placebo

Primary outcome

California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory
Time frame: Baseline, 6 weeks, 12 weeks, 24 weeks and at 52 weeks.
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).

4 secondary outcomes

Amplitude of Event Related Potentials (ERPs) P50 and P300
Time frame: Baseline, 12 Weeks
Latency of Event Related Potentials (ERPs) P50 and P300
Time frame: Baseline, 12 weeks
Number of Participants Who Experienced Post-traumatic Seizure During 12-week Treatment Window
Time frame: Baseline and weekly for 12 weeks.
Number of Participants With Self-reported Side Effects During 12-week Treatment Window
Time frame: Baseline and weekly for 12 weeks.

Results and safety

Results posted to the registry on 7 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Huperzine A	7	7
Placebo	7	5

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

Time frame: Baseline, 6 weeks, 12 weeks, 24 weeks and at 52 weeks.. Mean (Standard Deviation). Unit: score on a scale

Measure	Huperzine A n = 7	Placebo n = 5
CVLT-II-TL - Baseline	28.57 (12.35)	34.40 (18.73)
CVLT-II-TL - Week 6	31.43 (11.37)	45.00 (17.65)
CVLT-II-TL - Week 12	38.29 (14.20)	49.60 (18.27)
CVLT-II-TL - Week 24	33.29 (14.29)	44.60 (14.12)
CVLT-II-TL - Week 52	37.43 (11.30)	49.40 (15.00)
CVLT-II-SDFR - Baseline	3.86 (4.38)	5.80 (4.66)
CVLT-II-SDFR - Week 6	4.14 (3.53)	7.83 (4.12)
CVLT-II-SDFR - Week 12	6.29 (4.99)	10.40 (5.46)

Huperzine A vs Placebo: p = 0.38, Regression, Linear
Huperzine A vs Placebo: p = 0.38, Regression, Linear
Huperzine A vs Placebo: p = 0.42, Regression, Linear

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Huperzine A	2 of 7 (28.6%)	7 of 7 (100%)	0 of 7
Placebo	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6

Limitations and caveats (from the sponsor): Enrollment - not able to enroll target N, therefore small number of subjects analyzed. Neurophysiologic measures - difficulty collecting data from subjects for several reasons.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Traumatic Brain Injury

Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ross Zafonte, DO principal investigator

Spaulding Rehabilitation Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Huperzine A in people with Traumatic Brain Injury, run by Spaulding Rehabilitation Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory (time frame: Baseline, 6 weeks, 12 weeks, 24 weeks and at 52 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01676311.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2019.