Traumatic Brain InjuryNCT02025439

Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness

A study testing rTMS and Amantadine in people with Traumatic Brain Injury, run by Edward Hines Jr. VA Hospital at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to examine the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with Amantadine relative to rTMS Alone and Amantadine Alone for persons in chronic states of seriously impaired consciousness. Read more about this study

Who is it for?: Ages 18 to 64 years
Conditions the study is for: Traumatic Brain Injury
What is being tested?: rTMS and Amantadine
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: 2 sitesUnited States
Study dates: Feb 2014to Jul 2016
Phase: Interventional
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 64 years
All sexes
No healthy volunteers
Adult

Who may be able to join

18-64 years of age
Suffered a severe brain injury of traumatic origin at least 1-year prior to study enrollment
Remain in a state of disordered consciousness
Brain injuries will include injury with resulting coup-contre-coup injuries, excluding persons with trauma due to blunt injuries and/or non-traumatic encephalopathy

Who cannot join

Have 1 or more Amantadine contraindications: On monoamino oxidase inhibitor-B, hypersensitivity/idiosyncrasy to sympathomimetic amines, uncontrolled hypertension, glaucoma or Congestive Heart Failure
Have contraindications to Amantadine Dose of 200 mg Daily as determined by estimated Glomerular Filtration Rate (eGFR) ≤ 60 (ml/min)
Abnormal results of Liver Function Test at screening
Receiving anti-epileptic medications to control active seizures or have had a documented seizure within three months of study enrollment
Incurred large cortically based ischemic infarction/encephalomalacia subsequent to TBI
Have documented history of previous TBI, psychiatric illness (DSM criteria) and/or organic brain syndrome such as Alzheimer's

Show all 15Show fewer

Are using medications which may interfere with Amantadine and cannot be safely titrated or discontinued
Are pregnant
Have implanted cardiac pacemaker or defibrillator, cochlear implant, nerve stimulator, intracranial metal clips
Have MRI and/or TMS contraindications such as: History of claustrophobia, metal in eyes/face, shrapnel/bullet remnants in brain
Are fully conscious as indicated by a score of 6 on the Motor Function scale and/or a score of 2 on the Communication scale of the CRS-R,
Are within first year of injury
Are <18 years of age and > 65 years of age
Have an injury or condition due to blunt trauma only or non-traumatic encephalopathy
Have programmable CSF shunt or are ventilator dependent

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Northwestern Memorial Hospital
Chicago, Illinois, 60611
Edward Hines, Jr. VA Hospital
Hines, Illinois, 60141

Other trials in United States

About this study

Read the detailed description

The R21 research objective is to examine the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with Amantadine (TMS + Amantadine) relative to rTMS Alone and Amantadine Alone for persons in chronic states of seriously impaired consciousness. The hypothesis is that provision of rTMS+Amantadine will provide a safe yet synergistic effect that induces or accelerates functional recovery. This hypothesis is based on (a) preliminary data indicating partially improved neurobehavioral functioning mechanistically related to rTMS-induced neural activity and connectivity as well as improved integrity of white fiber tracts, (b) relationship between dopamine (DA) and common traumatic brain injury (TBI) impairments, (c) role of DA in mediating consciousness, (d) the commonality between and DA and rTMS-targeted pathways, (e) clinical efficacy and safety of Amantadine, (f) mechanisms of action of Amantadine, and (g) the association between rTMS and Amantadine with up-regulating brain derived neurotrophic factor. The rationale is that pairing rTMS with Amantadine will have a complementary and synergistic effect on factors promoting conscious behavior. The specific aims are to: (1) Demonstrate that rTMS+Amantadine is safely tolerated, (2) Determine neurobehavioral effect of rTMS+Amantadine, and (3) Characterize pre-and post-treatment neural changes in neural activation. Aim 1 is based on our preliminary safety data and safety data regarding Amantadine. To address Aims 2 \& 3 we use a repeated measures baseline control design with randomized treatment orders yielding three treatment groups; rTMS + Amantadine, rTMS Alone and Amantadine Alone. Analyses for Aims 2 and 3 involve comparing these treatment groups according to neurobehavioral growth trajectories, mean amount of neural activation and connectivity within and between brain regions, and indices of fiber tract directionality.

Conditions: Traumatic Brain Injury
Being tested: rTMS, Amantadine
Keywords: Traumatic Brain Injury, Transcranial Magnetic Stimulation, Amantadine, Vegetative State, Minimally Conscious State
Medical subject headings: Brain Injuries, Traumatic, Persistent Vegetative State

What participants receive

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

rTMSDevice
Also called Repetitive Transcranial Magnetic Stimulation
AmantadineDrug
Also called Symadine, Symmetrel

Study groups in NCT02025439
Study group	Role	What they receive
rTMS Alone followed by rTMS+AMA	Experimental	Subjects assigned to rTMS Alone will receive 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week.After first completing rTMS Alone, subjects will receive rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily. Receives: Device: rTMS; Drug: Amantadine
AMA Alone followed by rTMS+AMA	Experimental	Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days. After first completing Amantadine Alone subjects will receive rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily. Receives: Device: rTMS; Drug: Amantadine

What is being measured

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

Intensity of Adverse Event
If an adverse event occurred, the intensity was also indicated. The intensity of an adverse event was determined using a scale from 1-5 with 5 being the worst. The purpose of the study is to examine safety of rTMS combined with AMA relative to rTMS Alone and AMA alone. Results are not reported "per arm" rather, the arms are combined so as to compare the outcome when the interventions are provided separately (i.e., rTMS alone and amantadine alone) vs interventions are combined (rTMS +Amantadine alone).
Measured: 30 days after treatment "alone" and an additional 30 days after treatment "combined" (i.e., 60 days)

Timeline

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

Feb 2014Jul 2016

First posted1 Jan 2014 (estimated)
Study startFeb 2014
Primary completionJul 2016
Study completionJul 2016

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.
Publications (2)Papers the sponsor has linked to this study.
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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02025439
Sponsor's protocol ID: 1R21HD075192
Status last verified: Aug 2020
First submitted: 23 Dec 2013
Last updated: 24 Aug 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Pape TL, Rosenow J, Lewis G. Transcranial magnetic stimulation: a possible treatment for TBI. J Head Trauma Rehabil. 2006 Sep-Oct;21(5):437-51. doi: 10.1097/00001199-200609000-00063.
PubMed 16983227
Louise-Bender Pape T, Rosenow J, Lewis G, Ahmed G, Walker M, Guernon A, Roth H, Patil V. Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. Brain Stimul. 2009 Jan;2(1):22-35. doi: 10.1016/j.brs.2008.09.004. Epub 2008 Oct 23.
PubMed 20633400

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 24 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness
ClinicalTrials.gov ID: NCT02025439
Acronym / sponsor ID: 1R21HD075192
Conditions: Traumatic Brain Injury
Keywords: Traumatic Brain Injury, Transcranial Magnetic Stimulation, Amantadine, Vegetative State, Minimally Conscious State
Study type: Interventional
Recruitment status: Completed
Enrolment: 4 participants (actual)
Lead sponsor: Edward Hines Jr. VA HospitalUS federal agency
Study start: Feb 2014
Primary completion: Jul 2016 (actual)
Study completion: Jul 2016 (actual)
First posted: 1 Jan 2014 (estimated)
Results: Posted 24 Aug 2020

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
rTMS Alone followed by rTMS+AMA	Experimental	Device: rTMS, Drug: AmantadineSubjects assigned to rTMS Alone will receive 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week.After first completing rTMS Alone, subjects will receive rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily.
AMA Alone followed by rTMS+AMA	Experimental	Device: rTMS, Drug: AmantadineSubjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days. After first completing Amantadine Alone subjects will receive rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily.

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

18-64 years of age
Suffered a severe brain injury of traumatic origin at least 1-year prior to study enrollment
Remain in a state of disordered consciousness
Brain injuries will include injury with resulting coup-contre-coup injuries, excluding persons with trauma due to blunt injuries and/or non-traumatic encephalopathy

Key exclusion criteria (15 listed)

Have 1 or more Amantadine contraindications: On monoamino oxidase inhibitor-B, hypersensitivity/idiosyncrasy to sympathomimetic amines, uncontrolled hypertension, glaucoma or Congestive Heart Failure
Have contraindications to Amantadine Dose of 200 mg Daily as determined by estimated Glomerular Filtration Rate (eGFR) ≤ 60 (ml/min)
Abnormal results of Liver Function Test at screening
Receiving anti-epileptic medications to control active seizures or have had a documented seizure within three months of study enrollment
Incurred large cortically based ischemic infarction/encephalomalacia subsequent to TBI

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
rTMSAlso: Repetitive Transcranial Magnetic Stimulation	Device	AMA Alone followed by rTMS+AMA, rTMS Alone followed by rTMS+AMA
AmantadineAlso: Symadine, Symmetrel	Drug	AMA Alone followed by rTMS+AMA, rTMS Alone followed by rTMS+AMA

Primary outcome

Intensity of Adverse Event
Time frame: 30 days after treatment "alone" and an additional 30 days after treatment "combined" (i.e., 60 days)
If an adverse event occurred, the intensity was also indicated. The intensity of an adverse event was determined using a scale from 1-5 with 5 being the worst. The purpose of the study is to examine safety of rTMS combined with AMA relative to rTMS Alone and AMA alone. Results are not reported "per arm" rather, the arms are combined so as to compare the outcome when the interventions are provided separately (i.e., rTMS alone and amantadine alone) vs interventions are combined (rTMS +Amantadine alone).

Results and safety

Results posted to the registry on 24 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
rTMS Alone Followed by rTMS+AMA	2	2
AMA Alone Followed by rTMS+AMA	2	2

Primary outcome: Intensity of Adverse Event

Time frame: 30 days after treatment "alone" and an additional 30 days after treatment "combined" (i.e., 60 days). Mean (Standard Deviation). Unit: score on a scale

Measure	rTMS Alone n = 2	rTMS+AMA n = 4	AMA Alone n = 2
Value	0.5 (0.52)	0.98 (0.38)	0.33 (0.51)

rTMS Alone vs rTMS+AMA: Mean Difference (Final Values): 0.071, p <0.05, t-test, 2 sided

Population analysed: Results are reported both "per arm" at the end of 30 days when a single treatment (either rTMS or AMA) was ended, and additional results are reported with both arms combined to report the outcome after 60 days

Adverse events

Time frame: 3 months and 6 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
rTMS Alone	0 of 2 (0%)	2 of 2 (100%)	0 of 2
rTMS+AMA	0 of 4 (0%)	4 of 4 (100%)	0 of 4
AMA Alone	0 of 2 (0%)	2 of 2 (100%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16983227Pape TL, Rosenow J, Lewis G. Transcranial magnetic stimulation: a possible treatment for TBI. J Head Trauma Rehabil. 2006 Sep-Oct;21(5):437-51. doi: 10.1097/00001199-200609000-00063.
Background: PubMed 20633400Louise-Bender Pape T, Rosenow J, Lewis G, Ahmed G, Walker M, Guernon A, Roth H, Patil V. Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. Brain Stimul. 2009 Jan;2(1):22-35. doi: 10.1016/j.brs.2008.09.004. Epub 2008 Oct 23.

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.

Theresa BenderPape, DrPH principal investigator

Edward Hines Jr. VA Hospital

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

Questions about this trial

What is this clinical trial studying?

A study testing rTMS and Amantadine in people with Traumatic Brain Injury, run by Edward Hines Jr. VA Hospital at 2 sites 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 4 inclusion and 15 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: finished, as of the sponsor's last update on 24 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2020). 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?

Intensity of Adverse Event (time frame: 30 days after treatment "alone" and an additional 30 days after treatment "combined" (i.e., 60 days)). 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 NCT02025439, which also lists 2 linked publications.

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 24 Aug 2020.