Trial Outcomes & Findings for The Effects of Atomoxetine on Cognition and Brain Function Based on Catechol-O-methyltransferase(COMT) Genotype (NCT NCT00548327)
NCT ID: NCT00548327
Last Updated: 2013-06-14
Results Overview
Main outcome measures were BOLD fMRI response (activation) while performing a prefrontal cortex-dependent task such as N-Back Working Memory with increasing levels of task difficulty. It was expected to have a greater level of activation in BOLD fMRI in schizophrenic patients with respect to normal volunteers, and a greater activation in individuals (either normal volunteers or patients) who share the val/val genotype with respect to the met/met genotype. Based on prior fMRI studies and on power analysis of neuropsychological variables, at least 28 and 26 subjects are respectively needed to achieve significant power in functional neuroimaging and neuropsychological studies.These sizes provide an 80% power to observe significant differences between drug conditions at the 0.05 level.
TERMINATED
PHASE2
11 participants
2 hours after the first or the second dose of Atomoxetine or placebo on 14th day
2013-06-14
Participant Flow
Normal volunteers or patients with schizophrenia will be initially recruited from among individuals who have volunteered for previous genetic studies and for whom genetic data is already available. Power calculations set target accrual at 30 participants per genotype for 3 COMT genotypes per cohort (i.e., 90 patients and 90 healthy volunteers).
Subjects need to satisfy the inclusion/exclusion criteria for the genetic studies protocol before participating. Normal volunteers will be enrolled as outpatients and patients as inpatients. Females do both arms during the same phase of the menstrual cycle. Patients with Schizophrenia are stabilized for at least 6 weeks before the protocol.
Participant milestones
| Measure |
Healthy Participants
This is a double-blind, placebo-control, cross-over study of Atomoxetine in healthy volunteers. It includes 3 genotypes, the VAL/VAL, VAL/MET and MET/MET. Subjects are 2 weeks on placebo, 2 weeks on active compound and one week wash-out period between arms.
Amoxetine schedule: 25 mg Day 1 (or Day 22), 40 mg Day 2-3 (or Days 23-24), 60 mg Days 4-5 (or Days 25-26), 80 mg Days 6-14 (or Days 27-35).
Placebo schedule: Atomoxetine 25 mg Placebo Day 1 (or Day 22), Atomoxetine 40 mg Placebo Day 2-3 (or Days 23-24), Atomoxetine 60 mg Placebo Days 4-5 (or Days 25-26), Atomoxetine 80 mg Placebo Days 6-14 (or Days 27-35).
|
Patients With Schizophrenia
This is a double-blind, placebo-control, cross-over study of Atomoxetine in patients with schizophrenia. It includes 3 genotypes, the VAL/VAL, VAL/MET and MET/MET. Subjects are 2 weeks on placebo, 2 weeks on active compound and one week wash-out period between arms.
Amoxetine schedule: 25 mg Day 1 (or Day 22), 40 mg Day 2-3 (or Days 23-24), 60 mg Days 4-5 (or Days 25-26), 80 mg Days 6-14 (or Days 27-35).
Placebo schedule: Atomoxetine 25 mg Placebo Day 1 (or Day 22), Atomoxetine 40 mg Placebo Day 2-3 (or Days 23-24), Atomoxetine 60 mg Placebo Days 4-5 (or Days 25-26), Atomoxetine 80 mg Placebo Days 6-14 (or Days 27-35).
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
5
|
|
Overall Study
COMPLETED
|
6
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Healthy Participants
This is a double-blind, placebo-control, cross-over study of Atomoxetine in healthy volunteers. It includes 3 genotypes, the VAL/VAL, VAL/MET and MET/MET. Subjects are 2 weeks on placebo, 2 weeks on active compound and one week wash-out period between arms.
Amoxetine schedule: 25 mg Day 1 (or Day 22), 40 mg Day 2-3 (or Days 23-24), 60 mg Days 4-5 (or Days 25-26), 80 mg Days 6-14 (or Days 27-35).
Placebo schedule: Atomoxetine 25 mg Placebo Day 1 (or Day 22), Atomoxetine 40 mg Placebo Day 2-3 (or Days 23-24), Atomoxetine 60 mg Placebo Days 4-5 (or Days 25-26), Atomoxetine 80 mg Placebo Days 6-14 (or Days 27-35).
|
Patients With Schizophrenia
This is a double-blind, placebo-control, cross-over study of Atomoxetine in patients with schizophrenia. It includes 3 genotypes, the VAL/VAL, VAL/MET and MET/MET. Subjects are 2 weeks on placebo, 2 weeks on active compound and one week wash-out period between arms.
Amoxetine schedule: 25 mg Day 1 (or Day 22), 40 mg Day 2-3 (or Days 23-24), 60 mg Days 4-5 (or Days 25-26), 80 mg Days 6-14 (or Days 27-35).
Placebo schedule: Atomoxetine 25 mg Placebo Day 1 (or Day 22), Atomoxetine 40 mg Placebo Day 2-3 (or Days 23-24), Atomoxetine 60 mg Placebo Days 4-5 (or Days 25-26), Atomoxetine 80 mg Placebo Days 6-14 (or Days 27-35).
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
The Effects of Atomoxetine on Cognition and Brain Function Based on Catechol-O-methyltransferase(COMT) Genotype
Baseline characteristics by cohort
| Measure |
Healthy Participants
n=6 Participants
This is a double-blind, placebo-control, cross-over study of Atomoxetine in healthy volunteers. It includes 3 genotypes, the VAL/VAL, VAL/MET and MET/MET. Subjects are 2 weeks on placebo, 2 weeks on active compound and one week wash-out period between arms.
Amoxetine schedule: 25 mg Day 1 (or Day 22), 40 mg Day 2-3 (or Days 23-24), 60 mg Days 4-5 (or Days 25-26), 80 mg Days 6-14 (or Days 27-35).
Placebo schedule: Atomoxetine 25 mg Placebo Day 1 (or Day 22), Atomoxetine 40 mg Placebo Day 2-3 (or Days 23-24), Atomoxetine 60 mg Placebo Days 4-5 (or Days 25-26), Atomoxetine 80 mg Placebo Days 6-14 (or Days 27-35).
|
Patients With Schizophrenia
n=5 Participants
This is a double-blind, placebo-control, cross-over study of Atomoxetine in patients with schizophrenia. It includes 3 genotypes, the VAL/VAL, VAL/MET and MET/MET. Subjects are 2 weeks on placebo, 2 weeks on active compound and one week wash-out period between arms.
Amoxetine schedule: 25 mg Day 1 (or Day 22), 40 mg Day 2-3 (or Days 23-24), 60 mg Days 4-5 (or Days 25-26), 80 mg Days 6-14 (or Days 27-35).
Placebo schedule: Atomoxetine 25 mg Placebo Day 1 (or Day 22), Atomoxetine 40 mg Placebo Day 2-3 (or Days 23-24), Atomoxetine 60 mg Placebo Days 4-5 (or Days 25-26), Atomoxetine 80 mg Placebo Days 6-14 (or Days 27-35).
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<=18 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Age, Customized
Between 18 and 45 years
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Age, Customized
>=45 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 hours after the first or the second dose of Atomoxetine or placebo on 14th dayPopulation: Data were not collected for analysis because the study was terminated before target accrual
Main outcome measures were BOLD fMRI response (activation) while performing a prefrontal cortex-dependent task such as N-Back Working Memory with increasing levels of task difficulty. It was expected to have a greater level of activation in BOLD fMRI in schizophrenic patients with respect to normal volunteers, and a greater activation in individuals (either normal volunteers or patients) who share the val/val genotype with respect to the met/met genotype. Based on prior fMRI studies and on power analysis of neuropsychological variables, at least 28 and 26 subjects are respectively needed to achieve significant power in functional neuroimaging and neuropsychological studies.These sizes provide an 80% power to observe significant differences between drug conditions at the 0.05 level.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 2 hours after the first or the second dose of Atomoxetine or placebo on 14th dayPopulation: Data were not collected for analysis because the study was terminated before target accrual
Neuropsychological testing consists of a battery of 10-12 individual tests to measure cognitive function. We expect both a drug effect and a genotype effect on neuropsychological tasks that measure dorsolateral prefrontal cortex (DLPFC) executive function, mostly in individuals who share the val/val genotype with respect to the met/met genotype.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 14th and 35th daysPopulation: Data were not collected for analysis because the study was terminated before target accrual
The Positive and Negative Syndrome Scale (PANSS) is a 7-point rating scale with (1) indicating the absence of a symptom or behavior and (7) indicating the most severe symptom. The PANSS includes three scales(Positive and Negative Syndromes and General Psychopathology)and five clusters (Anergia, Thought Disturbance, Activation, Paranoid/Belligerence and Depression.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 14th and 35th daysPopulation: Data were not collected for analysis because the study was terminated before target accrual
The Profile of Mood States is an instrument that provides a rapid method of assessing transient, fluctuating mood states. The POMS consists of 65 adjectives rated by subjects on a 5-point scale and six factors that derive from this scale are: 1)tension-anxiety, 2)depression-dejection, 3)anger-hostility, 4)fatigue-inertia, 5)vigor-activity and 6)Confusion-bewilderment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 14th and 35th daysPopulation: Data were not collected for analysis because the study was terminated before target accrual
The Hamilton Anxiety Rating Scale is a psychological questionnaire to rate the severity of anxiety.It contains 14 symptom-oriented questions.Each of these symptoms is given a severity rating, from not present(scored as 0)to very severe(scored as 4)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: before and 3 hours after dosing on the 14th day receiving AtomoxetinePopulation: Data were not collected for analysis because the study was terminated before target accrual
Blood for drug plasma levels is obtained before and 3 hours after dosing on the 14th day receiving Atomoxetine.
Outcome measures
Outcome data not reported
Adverse Events
Atomoxetine-Patient
Placebo-Patient
Atomoxetine-Healthy Volunteer
Placebo-Healthy Volunteer
Serious adverse events
| Measure |
Atomoxetine-Patient
n=5 participants at risk
|
Placebo-Patient
n=5 participants at risk
|
Atomoxetine-Healthy Volunteer
n=6 participants at risk
|
Placebo-Healthy Volunteer
n=6 participants at risk
|
|---|---|---|---|---|
|
Psychiatric disorders
Psychosis
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
Other adverse events
| Measure |
Atomoxetine-Patient
n=5 participants at risk
|
Placebo-Patient
n=5 participants at risk
|
Atomoxetine-Healthy Volunteer
n=6 participants at risk
|
Placebo-Healthy Volunteer
n=6 participants at risk
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Loss of Appetite
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
33.3%
2/6 • Number of events 2 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Cardiac disorders
Palpitations
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Psychiatric disorders
Difficulty sleeping
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Gastrointestinal disorders
Dry Mouth
|
40.0%
2/5 • Number of events 2 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
40.0%
2/5 • Number of events 2 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
66.7%
4/6 • Number of events 4 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
40.0%
2/5 • Number of events 2 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Psychiatric disorders
Fatigue
|
40.0%
2/5 • Number of events 2 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
40.0%
2/5 • Number of events 2 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
50.0%
3/6 • Number of events 3 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Reproductive system and breast disorders
Sexual dysfuntion
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Renal and urinary disorders
Urinary difficulties
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Skin and subcutaneous tissue disorders
Sweating
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Nervous system disorders
Dizziness
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Nervous system disorders
Restlessness
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Gastrointestinal disorders
Heartburn
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
20.0%
1/5 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
General disorders
Chills
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Skin and subcutaneous tissue disorders
Itching
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
|
Psychiatric disorders
unusual thoughts
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/5 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
16.7%
1/6 • Number of events 1 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
0.00%
0/6 • Two years, from 2008 to 2011.
Adverse events are collected during the arm or at the end of each arm.
|
Additional Information
Jose A. Apud MD, PhD
Clinical Brain Disoders Branch-National Institute of Mental Health (NIMH)-National Institute of Health (NIH)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place