Traumatic Brain InjuryPhase 4NCT00693121
Amantadine for Treatment of Symptoms of the Post-traumatic Confusional State
A Phase 4 study testing Amantadine hydrochloride in people with Traumatic Brain Injury and Posttraumatic Confusional State, run by Methodist Rehabilitation Center at 1 site in United States.
Trial summary
Patients with traumatic brain injury often experience a period of acute confusion that may include agitation as they recover from their injuries. While this confusion generally resolves with time, patients may pose increased risk of injury to themselves or others during this period. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Traumatic Brain Injury, Posttraumatic Confusional State, Delirium
- What is being tested?
- Amantadine hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2003to Mar 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Acute Traumatic Brain Injury (≤90 days postinjury)
- Responsive (not fulfilling criteria for Minimally Conscious State)
- Meet PTCS criteria on 2 consecutive examinations (as determined by the Confusion Assessment Protocol)
- Initial neurorehabilitation hospital admission
- Anticipated ≥2 week length-of-stay after meeting PTCS criteria
Who cannot join
- Preexisting seizure disorder
- Prior history of hospitalization for psychiatric condition
Trial locations and contacts
1 site in 1 country.
United States1 site
Methodist Rehabilitation Center
Jackson, Mississippi, 39216
About this study
Official title: Amantadine Hydrochloride for Treatment of Symptoms of the Post-traumatic Confusional State Among Neurorehabilitation Admissions With TBI: A Randomized, Double-Blind, Placebo-Controlled Trial
Patients with traumatic brain injury often experience a period of acute confusion that may include agitation as they recover from their injuries. While this confusion generally resolves with time, patients may pose increased risk of injury to themselves or others during this period. Their behavior may also increase stress for family members and interfere with their ability to benefit from rehabilitation therapies. A number of different medications have been used to treat confusion to decrease agitation, decrease risk of injury, and improve participation in rehabilitation therapies. To this point, there has not been a research or scientific basis for knowing which medication is the best for a specific patient. The overall goal of this study is to conduct a scientific investigation to help determine which medication works best to treat confusion.
Study hypothesis: Amantadine will reduce the severity and number of symptoms of acute confusion after traumatic brain injury.
Read the detailed description
Patients with TBI who require inpatient rehabilitation are frequently confused at the time of admission for rehabilitation. Our investigations of confusion conducted as part of the TBIMSM have clarified the nature of confusion in early recovery after TBI. Early confusion (PTCS) has been found to be a complex syndrome characterized by disorientation, cognitive impairment, restlessness, decreased level of daytime arousal, sleep disturbance, fluctuation of symptoms, and psychotic-type symptoms. PTCS complicates early management of patients with TBI, and may contribute to increased risk of injury to patients and hospital staff, increased stress among family members and staff, decreased participation in therapies, increased cost of care, and an increased likelihood of being discharged to psychiatric or long-term care settings. These facts indicate the need for effective management of PTCS. Consensus regarding optimal treatment of the cognitive and behavioral symptoms encountered among patients with PTCS does not exist currently. While many agents have been tried to address such symptoms in TBI, few have been investigated systematically. These circumstances indicate the need for appropriate clinical trials to provide guidance to clinicians for medical treatment of PTCS. In response, the NIDRR-Traumatic Brain Injury Model System of Mississippi proposed a randomized, double-blinded, placebo-controlled, parallel group trial for the pharmacological treatment of PTCS. The agent selected for this clinical trial is amantadine, an NMDA and indirect dopamine agonist. This agent will be compared to placebo on response measures of efficacy and safety.
Study hypothesis: Amantadine will reduce the severity and number of symptoms of PTCS.
- Being tested
- Amantadine hydrochloride, Placebo capsule
- Keywords
- Traumatic Brain Injury, Posttraumatic Confusional State, Delirium, Amantadine, Clinical trial
- Medical subject headings
- Brain Injuries, Traumatic, Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amantadine hydrochlorideDrug
100mg administered orally twice daily x 14 days
Placebo capsuleDrug
capsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Identical capsule to amantadine hydrochloride active intervention, administered twice daily x 14 days Receives: Drug: Placebo capsule |
| Amantadine | Active comparator | Amantadine hydrochloride 100mg capsule administered twice daily x 14 days Receives: Drug: Amantadine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confusion Assessment Protocol (number of symptoms)
Measured: 14 days
Secondary outcomes (2)
number of participants withdrawn from study due to fulfillment of "escape criteria"
Measured: 14 days
Time to reach "non-confused" Confusion Assessment Protocol score
Measured: <14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2008 (estimated)
- Study startApr 2003
- Primary completionNov 2007
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Methodist Rehabilitation Center
- Sponsor type
- University, hospital or other
- Collaborators
- U.S. Department of Education
- Investigators
- Stuart A Yablon, M.D., Principal investigator, Brain Injury Program, Methodist Rehabilitation CenterMark Sherer, Ph.D., Study director, Department of Research, Memorial Hermann/TIRR, Houston, TXRisa N Richardson, Ph.D., Study director, Polytrauma Program, James A. Haley Veterans Hospital, Tampa, FL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00693121
- Sponsor's protocol ID
- MethodistRC Project 1
- Other IDs
- NIDRR grant #: H133A020514
- Status last verified
- Jun 2008
- First submitted
- 4 Jun 2008
- Last updated
- 18 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Sherer M, Yablon SA, Nakase-Richardson R, Nick TG. Effect of severity of post-traumatic confusion and its constituent symptoms on outcome after traumatic brain injury. Arch Phys Med Rehabil. 2008 Jan;89(1):42-7. doi: 10.1016/j.apmr.2007.08.128.
PubMed 18164329Nakase-Richardson R, Yablon SA, Sherer M. Prospective comparison of acute confusion severity with duration of post-traumatic amnesia in predicting employment outcome after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):872-6. doi: 10.1136/jnnp.2006.104190. Epub 2006 Dec 18.
PubMed 17178822Sherer M, Nakase-Thompson R, Yablon SA, Gontkovsky ST. Multidimensional assessment of acute confusion after traumatic brain injury. Arch Phys Med Rehabil. 2005 May;86(5):896-904. doi: 10.1016/j.apmr.2004.09.029.
PubMed 15895334Nakase-Thompson R, Sherer M, Yablon SA, Nick TG, Trzepacz PT. Acute confusion following traumatic brain injury. Brain Inj. 2004 Feb;18(2):131-42. doi: 10.1080/0269905031000149542.
PubMed 14660226
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amantadine Hydrochloride for Treatment of Symptoms of the Post-traumatic Confusional State Among Neurorehabilitation Admissions With TBI: A Randomized, Double-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT00693121
- Acronym / sponsor ID
- MethodistRC Project 1
- Keywords
- Traumatic Brain Injury, Posttraumatic Confusional State, Delirium, Amantadine, Clinical trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Methodist Rehabilitation CenterUniversity, hospital or other
- Collaborators
- U.S. Department of Education
- Study start
- Apr 2003
- Primary completion
- Nov 2007 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 6 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with traumatic brain injury often experience a period of acute confusion that may include agitation as they recover from their injuries. While this confusion generally resolves with time, patients may pose increased risk of injury to themselves or others during this period. Their behavior may also increase stress for family members and interfere with their ability to benefit from rehabilitation therapies. A number of different medications have been used to treat confusion to decrease agitation, decrease risk of injury, and improve participation in rehabilitation therapies. To this point, there has not been a research or scientific basis for knowing which medication is the best for a specific patient. The overall goal of this study is to conduct a scientific investigation to help determine which medication works best to treat confusion.
Study hypothesis: Amantadine will reduce the severity and number of symptoms of acute confusion after traumatic brain injury.
Detailed description
Patients with TBI who require inpatient rehabilitation are frequently confused at the time of admission for rehabilitation. Our investigations of confusion conducted as part of the TBIMSM have clarified the nature of confusion in early recovery after TBI. Early confusion (PTCS) has been found to be a complex syndrome characterized by disorientation, cognitive impairment, restlessness, decreased level of daytime arousal, sleep disturbance, fluctuation of symptoms, and psychotic-type symptoms. PTCS complicates early management of patients with TBI, and may contribute to increased risk of injury to patients and hospital staff, increased stress among family members and staff, decreased participation in therapies, increased cost of care, and an increased likelihood of being discharged to psychiatric or long-term care settings. These facts indicate the need for effective management of PTCS. Consensus regarding optimal treatment of the cognitive and behavioral symptoms encountered among patients with PTCS does not exist currently. While many agents have been tried to address such symptoms in TBI, few have been investigated systematically. These circumstances indicate the need for appropriate clinical trials to provide guidance to clinicians for medical treatment of PTCS. In response, the NIDRR-Traumatic Brain Injury Model System of Mississippi proposed a randomized, double-blinded, placebo-controlled, parallel group trial for the pharmacological treatment of PTCS. The agent selected for this clinical trial is amantadine, an NMDA and indirect dopamine agonist. This agent will be compared to placebo on response measures of efficacy and safety.
Study hypothesis: Amantadine will reduce the severity and number of symptoms of PTCS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo capsuleIdentical capsule to amantadine hydrochloride active intervention, administered twice daily x 14 days |
| Amantadine | Active comparator | Drug: Amantadine hydrochlorideAmantadine hydrochloride 100mg capsule administered twice daily x 14 days |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Acute Traumatic Brain Injury (≤90 days postinjury)
- Responsive (not fulfilling criteria for Minimally Conscious State)
- Meet PTCS criteria on 2 consecutive examinations (as determined by the Confusion Assessment Protocol)
- Initial neurorehabilitation hospital admission
- Anticipated ≥2 week length-of-stay after meeting PTCS criteria
Key exclusion criteria (2 listed)
- Preexisting seizure disorder
- Prior history of hospitalization for psychiatric condition
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 |
|---|---|---|
| Amantadine hydrochloride100mg administered orally twice daily x 14 days | Drug | Amantadine |
| Placebo capsulecapsule, identical to amantadine hydrochloride capsule, administered twice daily x 14 days | Drug | Placebo |
Primary outcome
Confusion Assessment Protocol (number of symptoms)
Time frame: 14 days
2 secondary outcomes
number of participants withdrawn from study due to fulfillment of "escape criteria"
Time frame: 14 days
Time to reach "non-confused" Confusion Assessment Protocol score
Time frame: <14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2023.
- Background: PubMed 18164329Sherer M, Yablon SA, Nakase-Richardson R, Nick TG. Effect of severity of post-traumatic confusion and its constituent symptoms on outcome after traumatic brain injury. Arch Phys Med Rehabil. 2008 Jan;89(1):42-7. doi: 10.1016/j.apmr.2007.08.128.
- Background: PubMed 17178822Nakase-Richardson R, Yablon SA, Sherer M. Prospective comparison of acute confusion severity with duration of post-traumatic amnesia in predicting employment outcome after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):872-6. doi: 10.1136/jnnp.2006.104190. Epub 2006 Dec 18.
- Background: PubMed 15895334Sherer M, Nakase-Thompson R, Yablon SA, Gontkovsky ST. Multidimensional assessment of acute confusion after traumatic brain injury. Arch Phys Med Rehabil. 2005 May;86(5):896-904. doi: 10.1016/j.apmr.2004.09.029.
- Background: PubMed 14660226Nakase-Thompson R, Sherer M, Yablon SA, Nick TG, Trzepacz PT. Acute confusion following traumatic brain injury. Brain Inj. 2004 Feb;18(2):131-42. doi: 10.1080/0269905031000149542.
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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.
Stuart A Yablon, M.D. principal investigator
Brain Injury Program, Methodist Rehabilitation Center
Mark Sherer, Ph.D. study director
Department of Research, Memorial Hermann/TIRR, Houston, TX
Risa N Richardson, Ph.D. study director
Polytrauma Program, James A. Haley Veterans Hospital, Tampa, FL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amantadine hydrochloride in people with Traumatic Brain Injury and Posttraumatic Confusional State, run by Methodist Rehabilitation Center 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 5 inclusion and 2 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 18 Oct 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Confusion Assessment Protocol (number of symptoms) (time frame: 14 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 NCT00693121, which also lists 4 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 18 Oct 2023.