CClinicalTrials.gg
Sign In
CompletedNCT00779324Updated Jul 12, 2022Results posted

Amantadine for the Treatment of Traumatic Brain Injury Irritability and Aggression: A Multi-site Study

An interventional study of Amantadine Hydrochloride and Placebo in Brain Injury and Aggression, sponsored by Wake Forest University Health Sciences. Completed at 6 sites in United States. Open to participants aged 16 Years to 75 Years. Per ClinicalTrials.gov, last updated 2022-07-12.

Sponsored by Wake Forest University Health Sciences · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
168
Allocation
Randomized
Ages
16 Years to 75 Years
Sex
All
01

Study summary

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

Read the detailed description

PURPOSE OF PROJECT: To study the effect of amantadine 100 mg administered twice daily compared to placebo on irritability from baseline to treatment Day 28.

SUMMARY OF PROJECT: It is anticipated that 168 subjects with 168 corresponding subject informants will be recruited for the study. Carolinas Rehabilitation, the lead center, and 5 collaborating centers will enroll approximately 28 subjects each.

Subjects will be recruited primarily from the clinics. Also, letters will be sent to patients in our data base. If the first encounter with research personnel is by telephone, the research assistant will obtain verbal (telephone) consent from the subject's informant for the Neuropsychiatric Inventory (NPI) for subject irritability. The score on this questionnaire must be ≥ 6 for qualification. This allows pre-screening to take place and avoid an unnecessary clinic visit.

Subjects who consent and qualify will be randomized in a 1:1 ratio, amantadine to placebo. Stratification to randomization group will occur based on the presence of depression defined by a Beck's Depression Inventory-II (BDI-II) score ≥ 13. Randomized subjects will receive amantadine or placebo 100 mg twice daily every morning and 12 Noon. There will be 4 clinic visits. Visits will occur at baseline, for consenting and screening, day 28, day 60 and day 90. At all 4 clinic visits, both the subject and the informant will be given questionnaires regarding the subject's behavior and mood. Follow up phone calls will occur each week that the subject is not seen in the clinic until the end of the study. Follow up phone calls will assess for study medication compliance, adverse events and concomitant medication changes. Day 60 ends the period of the Randomized Clinical Trial phase of the study and the subjects will begin the 1 month continuation phase of the study when all participants receive active amantadine.

The following questionnaires will be used as measures of irritability for the subject and the informant: Neuropsychiatric Inventory (NPI), State Trait Anger Expression Inventory (STAXI-2), and Global Impression of Change.

The following questionnaires will be dispensed to the subject only: Short Form -12, Satisfaction With Life Scale, Patient Health Questionnaire, Beck Depression Inventory, Brief Symptom Inventory, Family Assessment Device, Fatigue Impact Scale, and tests of cognitive function. The Glasgow Outcome Score-Extended will be completed by the research assistant using information obtained primarily from the informant.

The Investigator will complete the Clinical Global Impression of change at Visits 1, 2, 3, and 4.

History and Physical Exam, creatinine level (kidney function) will be obtained for safety and tolerability. Serum pregnancy tests will be drawn at screening for females of childbearing potential.

02

Conditions studied

  • Brain Injury
  • Aggression

Keywords

  • traumatic brain injury
  • irritability
  • aggression
  • amantadine
  • behavior
03

In context

Brain Injuries

2,113 studies on the registry are indexed under Brain Injuries; 385 are open to participants now.

This study's enrollment of 168 is above the median of 48 across 1,331 interventional studies indexed under Brain Injuries.

Browse Brain Injuries studies →

Lead sponsor

Wake Forest University Health Sciences is the lead sponsor of 1,320 studies on the registry; 199 are open to participants now.

Of its 323 completed or terminated interventional studies of FDA-regulated products, 243 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
16 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
168 participants (actual)

Study arms

  • Experimental
    Amantadine

    Amantadine 100 mg every morning and Noon

    Drug: Amantadine Hydrochloride

  • Placebo comparator
    Placebo

    Placebo tablets

    Drug: Placebo

Interventions

  • DrugAmantadine Hydrochloride

    100 mg every morning and noon

    Also known as: Symmetrel

  • DrugPlacebo

    one placebo tablet every morning and 12 Noon

06

What researchers measure

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).

    Time frame: Day 28

Secondary outcomes

  1. Change in Neuropsychiatric Inventory - Irritability Domain Assessed 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).

    Time frame: Day 28

  2. Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant 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).

    Time frame: Day 28

  3. Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants 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).

    Time frame: Day 28

  4. Clinical Global Impressions Day 28

    Study physician's impression of change since study onset. Clinicians Global Impressions of Change (CGI) is a sensitive, standardized tool to assess psychopharmacologic treatment response completed by the study physician. The Global Improvement (GI) CGI subscale documented the clinician's impression of change. The GI uses a 7-point scale to assess beneficial and negative effects. Low GI values (1 -3) indicate improvement; higher values (4-7) represent worsening.

    Time frame: 28 Days

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

    As described above for the primary measure, assessed as a secondary measure at Day 60. 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).

    Time frame: 60 days

  6. Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 60

    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).

    Time frame: Day 60

  7. Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observers Day 60

    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).

    Time frame: Day 60

  8. Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 60

    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).

    Time frame: Day 60

  9. Clinical Global Impressions Day 60

    Study physician's impression of change since study onset. Clinicians Global Impressions of Change (CGI) is a sensitive, standardized tool to assess psychopharmacologic treatment response completed by the study physician. The Global Improvement (GI) CGI subscale documented the clinician's impression of change. The GI uses a 7-point scale to assess beneficial and negative effects. Low GI values (1 -3) indicate improvement; higher values (4-7) represent worsening.

    Time frame: 60 days

07

Results

Posted Sep 10, 2021

Participant flow

Participant recruitment occurred 2009 - 2013 via referrals, letters from physicians, newsletters, and local brain injury support groups.

Participant flow — Overall Study
MilestoneAmantadinePlacebo
Started8286
Completed 28-day mid-point8081
Completed7582
Not completed74
Withdrew: Lost to follow-up21
Withdrew: Withdrawal by subject42
Withdrew: Missed visit11

Outcome measures

PrimaryProportion 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).

Time frame:
Day 28
Reported as:
Number · percentage of participants NPI improve>2
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Observer Day 28
percentage of participants NPI improve>2AmantadinePlacebo
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Observer Day 2866.366.7
Statistical analysis
  • Amantadine vs Placebo · Chi-squared · p = 0.9554 · Difference in percents: -0.4 · 95% CI -14.7 to 13.9
SecondaryChange in Neuropsychiatric Inventory - Irritability Domain Assessed 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).

Time frame:
Day 28
Reported as:
Median · score on a scale
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observer Day 28
score on a scaleAmantadinePlacebo
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observer Day 28-4 ± 3.39-4 ± 3.36
Statistical analysis
  • Amantadine vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.96
SecondaryProportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant 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).

Time frame:
Day 28
Reported as:
Number · percentage of participants NPI improve>2
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 28
percentage of participants NPI improve>2AmantadinePlacebo
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 2851.340.5
Statistical analysis
  • Amantadine vs Placebo · Chi-squared · p = 0.1662 · Difference in percents: 10.8 · 95% CI -4.2 to 25.8
SecondaryChange in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants 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).

Time frame:
Day 28
Reported as:
Median · score on a scale
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 28
score on a scaleAmantadinePlacebo
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 28-3 ± 3.58-2 ± 3.9
Statistical analysis
  • Amantadine vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.3488
SecondaryClinical Global Impressions Day 28

Study physician's impression of change since study onset. Clinicians Global Impressions of Change (CGI) is a sensitive, standardized tool to assess psychopharmacologic treatment response completed by the study physician. The Global Improvement (GI) CGI subscale documented the clinician's impression of change. The GI uses a 7-point scale to assess beneficial and negative effects. Low GI values (1 -3) indicate improvement; higher values (4-7) represent worsening.

Time frame:
28 Days
Reported as:
Median · score on a scale
Clinical Global Impressions Day 28
score on a scaleAmantadinePlacebo
Clinical Global Impressions Day 283.00 ± 1.143.00 ± 0.92
SecondaryProportion of Participants With >2-point Increase on Neuropsychiatric Inventory Irritability Domain Rated by Observers Day 60

As described above for the primary measure, assessed as a secondary measure at Day 60. 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).

Time frame:
60 days
Reported as:
Number · percentage of participants NPI improve>2
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory Irritability Domain Rated by Observers Day 60
percentage of participants NPI improve>2AmantadinePlacebo
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory Irritability Domain Rated by Observers Day 6074.768.3
Statistical analysis
  • Amantadine vs Placebo · Chi-squared · p = 0.38 · Difference in percents: 6.4 · 95% CI -7.2 to 20
SecondaryProportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 60

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).

Time frame:
Day 60
Reported as:
Number · percentage of participants NPI improve>2
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 60
percentage of participants NPI improve>2AmantadinePlacebo
Proportion of Participants With >2-point Increase on Neuropsychiatric Inventory - Irritability Domain Rated by Participant Day 6060.548.8
Statistical analysis
  • Amantadine vs Placebo · Chi-squared · p = 0.1373 · Difference in percents: 11.7 · 95% CI -3.3 to 26.7
SecondaryChange in Neuropsychiatric Inventory - Irritability Domain Assessed by Observers Day 60

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).

Time frame:
Day 60
Reported as:
Median · score on a scale
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observers Day 60
score on a scaleAmantadinePlacebo
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Observers Day 60-5 ± 3.12-4 ± 3.42
Statistical analysis
  • Amantadine vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.12
SecondaryChange in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 60

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).

Time frame:
Day 60
Reported as:
Median · score on a scale
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 60
score on a scaleAmantadinePlacebo
Change in Neuropsychiatric Inventory - Irritability Domain Assessed by Participants Day 60-3 ± 2.83-2 ± 2.83
Statistical analysis
  • Amantadine vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.0353
SecondaryClinical Global Impressions Day 60

Study physician's impression of change since study onset. Clinicians Global Impressions of Change (CGI) is a sensitive, standardized tool to assess psychopharmacologic treatment response completed by the study physician. The Global Improvement (GI) CGI subscale documented the clinician's impression of change. The GI uses a 7-point scale to assess beneficial and negative effects. Low GI values (1 -3) indicate improvement; higher values (4-7) represent worsening.

Time frame:
60 days
Reported as:
Median · score on a scale
Clinical Global Impressions Day 60
score on a scaleAmantadinePlacebo
Clinical Global Impressions Day 603.00 ± 1.053.00 ± 1.08

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Amantadine—3/82 (3.7%)36/82 (43.9%)
Placebo—2/86 (2.3%)33/86 (38.4%)
Most frequent serious events
Most frequent serious events
EventAmantadinePlacebo
Urinary tract infectionInfections and infestations1/820/86
ParanoiaPsychiatric disorders1/820/86
Other general medicalGeneral disorders1/820/86
Myocardial infarctionCardiac disorders0/821/86
Other infectionInfections and infestations0/821/86
Most frequent other events
Most frequent other events
EventAmantadinePlacebo
Other general medicalGeneral disorders10/8213/86
Insomnia/ sleep disturbanceNervous system disorders7/8210/86
ConnstipationGastrointestinal disorders6/821/86
OtherGeneral disorders3/826/86
headacheNervous system disorders5/822/86
DiarrheaGastrointestinal disorders5/821/86

Baseline characteristics

Age, Continuous
Age, Continuous(years)AmantadinePlaceboTotal
Mean40.18 ± 12.6738.23 ± 12.3639.21 ± 12.52
Sex: Female, Male
Sex: Female, Male(Participants)AmantadinePlaceboTotal
Female182038
Male6466130
08

Study locations

6 sites
  • Indiana University and the Rehabilitation Hospital of Indiana
    Indianapolis, Indiana 46254, United States
  • Spaulding Rehabilitation
    Boston, Massachusetts 02114, United States
  • Carolinas Rehabilitation
    Charlotte, North Carolina 28203, United States
  • The Ohio State University
    Columbus, Ohio 43210, United States
  • TIRR Memorial Herman
    Houston, Texas 77030, United States
  • University of Washington
    Seattle, Washington 98195, United States
09

References and documents

Publications

  • 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. PubMed 29742960 ↗
  • 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. PubMed 28891908 ↗
  • 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. PubMed 25774566 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 12, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00779324
Lead sponsor
Wake Forest University Health Sciences
Collaborators
Indiana University, University of Washington, The Institute for Rehabilitaion and Research Foundation, Spaulding Rehabilitation Hospital, Ohio State University, Icahn School of Medicine at Mount Sinai
Responsible party
Sponsor
First posted
Oct 24, 2008
Start date
Aug 2009
Primary completion
Apr 2013
Completion
May 2013
Results posted
Sep 10, 2021
Last update
Jul 12, 2022

Study contacts

Flora M Hammond, MD
principal investigator · Carolinas Rehabilitation

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Brain Injuries→

Other studies from this sponsor

Wake Forest University Health Sciences

Start the discussion