NCT00779324

Brief Summary

The purpose of this study is to study the effect of amantadine on irritability and aggression caused by traumatic brain injury.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
168

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Aug 2009

Longer than P75 for not_applicable

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 23, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 24, 2008

Completed
9 months until next milestone

Study Start

First participant enrolled

August 1, 2009

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2013

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2013

Completed
8.4 years until next milestone

Results Posted

Study results publicly available

September 10, 2021

Completed
Last Updated

July 12, 2022

Status Verified

August 1, 2021

Enrollment Period

3.7 years

First QC Date

October 23, 2008

Results QC Date

September 18, 2015

Last Update Submit

July 8, 2022

Conditions

Brain InjuryAggression

Keywords

traumatic brain injuryirritabilityaggressionamantadinebehavior

Outcome Measures

Primary Outcomes (1)

  • Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Observer Day 28

    The Neuropsychiatric Inventory (NPI) is a 40-item rating scale developed to assess 12 behavioral domains. Only the NPI-Irritability (NPI-I) domain was used for this study. NPI-I measures irritability with items including: bad temper, rapid mood changes, sudden anger, impatience, crankiness, argumentative. The rater selects the frequency (1-3) and severity (1-4) of the most problematic of these behavioral aspect(s) over the preceding month. The NPI score is the product of the frequency and severity for the NPI most problematic item score. The primary outcome measure was the proportion of participants with greater than two-point increase on the Neuropsychiatric Inventory Irritability domain. The total range is 1 (least irritability) - 12 (worst irritability).

    Day 28

Secondary Outcomes (9)

  • Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observer Day 28

    Day 28

  • Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 28

    Day 28

  • Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 28

    Day 28

  • Clinical Global Impressions Day 28

    28 Days

  • Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory Irritability Domain Rated by Observers Day 60

    60 days

  • +4 more secondary outcomes

Study Arms (2)

Amantadine

EXPERIMENTAL

Amantadine 100 mg every morning and Noon

Drug: Amantadine Hydrochloride

Placebo

PLACEBO COMPARATOR

Placebo tablets

Drug: Placebo

Interventions

Amantadine HydrochlorideDRUG

100 mg every morning and noon

Also known as: Symmetrel
Amantadine
PlaceboDRUG

one placebo tablet every morning and 12 Noon

Placebo

Eligibility Criteria

Age16 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Closed head injury (defined as impaired brain function resulting from externally inflicted trauma without penetrating injury) at least 6 months prior to enrollment
  • Irritability that is either new or worse than the level of irritability before the traumatic brain injury, by report of the Observer or person with TBI
  • Age at time of enrollment: 16 to 75 years
  • Voluntary informed consent and authorization of participant and informant
  • Subject and informant willing to comply with the protocol
  • Informant-rated NPI Irritability Domain score 6 or greater (moderate-to-severe irritability)
  • Medically and neurologically stable during the month prior to enrollment
  • If taking antidepressant, anxiolytic, hypnotic, or stimulant medications, no change anticipated in these medications during the month prior to enrollment or during the 90-day participation
  • No change in therapies or medications planned during the 90-day participation
  • No surgeries planned during the 90-day participation
  • Vision, hearing, speech, motor function, and comprehension sufficient to complete interviews
  • Observer (e.g.: family member, close friend, employer) with whom subject interacts sufficiently to observe occurrences of irritability. The observer interacts with the participant for a period long enough and of a nature to be able to judge the participant's irritability. The interactions would need to be adequate to judge observer distress over the irritability, severity of irritability and frequency of irritability on the following scale: \< once weekly; once per week; several times per week, but not every day; essentially continuous.

You may not qualify if:

  • Previous participation in the Carolinas TBI Model System amantadine irritability study
  • Ingestion of amantadine hydrochloride during the month prior to enrollment
  • Potential subject without a reliable informant
  • Penetrating head injury as defined by head injury due to gunshot, projectile or foreign object
  • Injury \< 6 months prior to enrollment
  • Inability to interact sufficiently for communication with caregiver
  • Clinical signs of active infection
  • Diagnosis of seizure in the month prior to enrollment
  • Creatinine clearance \<60 mL/min
  • Pregnancy (Beta-HCG + females of child-bearing potential) and lactating females
  • Concurrent use of first generation neuroleptic agents or phenelzine
  • History of schizophrenia or psychosis
  • Active concern of schizophrenia or psychosis
  • Diagnosis of progressive or additional neurologic disease that affects brain function, except stroke that occurs at th same time as the TBI
  • Previous allergy or adverse reaction to amantadine hydrochloride

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Indiana University and the Rehabilitation Hospital of Indiana

Indianapolis, Indiana, 46254, United States

Location

Spaulding Rehabilitation

Boston, Massachusetts, 02114, United States

Location

Carolinas Rehabilitation

Charlotte, North Carolina, 28203, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

TIRR Memorial Herman

Houston, Texas, 77030, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (3)

  • Hammond FM, Sherer M, Malec JF, Zafonte RD, Dikmen S, Bogner J, Bell KR, Barber J, Temkin N. Amantadine Did Not Positively Impact Cognition in Chronic Traumatic Brain Injury: A Multi-Site, Randomized, Controlled Trial. J Neurotrauma. 2018 Oct 1;35(19):2298-2305. doi: 10.1089/neu.2018.5767. Epub 2018 Jun 7.

    PMID: 29742960DERIVED

  • Hammond FM, Malec JF, Zafonte RD, Sherer M, Bogner J, Dikmen S, Whitney MP, Bell KR, Perkins SM, Moser EA. Potential Impact of Amantadine on Aggression in Chronic Traumatic Brain Injury. J Head Trauma Rehabil. 2017 Sep/Oct;32(5):308-318. doi: 10.1097/HTR.0000000000000342.

    PMID: 28891908DERIVED

  • Hammond FM, Sherer M, Malec JF, Zafonte RD, Whitney M, Bell K, Dikmen S, Bogner J, Mysiw J, Pershad R; Amantadine Irritability Multisite Study Group. Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study. J Neurotrauma. 2015 Aug 15;32(16):1230-8. doi: 10.1089/neu.2014.3803. Epub 2015 Mar 31.

    PMID: 25774566DERIVED

Related Links

MeSH Terms

Conditions

Brain InjuriesAggressionBrain Injuries, TraumaticBehavior

Interventions

Amantadine

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and InjuriesAberrant Motor Behavior in DementiaBehavioral SymptomsSocial Behavior

Intervention Hierarchy (Ancestors)

AdamantaneBridged-Ring CompoundsHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Results Point of Contact

Title
Flora Hammond, MD
Organization
Indiana University School of Medicine
flora.hammond@rhin.com
3173292106

Study Officials

  • Flora M Hammond, MD

    Carolinas Rehabilitation

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 23, 2008

First Posted

October 24, 2008

Study Start

August 1, 2009

Primary Completion

April 1, 2013

Study Completion

May 1, 2013

Last Updated

July 12, 2022

Results First Posted

September 10, 2021

Record last verified: 2021-08

Locations

US(6)