PEACE: Pilot Evaluation of Atomoxetine on Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Adolescents With Cannabis abusE
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether atomoxetine is effective in reducing ADHD (Attention Deficit/Hyperactivity Disorder) symptoms in adolescents with ADHD and comorbid cannabis abuse.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
In the past adolescents with cannabis abuse have been excluded from studies in which atomoxetine for ADHD symptoms was studied. In this study the efficacy of atomoxetine on symptoms of ADHD in adolescents with ADHD and comorbid cannabis abuse will be studied.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Atomoxetine 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
Drug: Atomoxetine
0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale-IV-Parent Version: Investigator Scored Total Score at 12 Weeks [12 weeks]
Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. Higher scores indicate greater impairment. The scale is scored by an investigator while interviewing the parent.
Secondary Outcome Measures
- Clinical Global Impression-ADHD-Improvement (CGI-ADHD-I) at 12 Weeks [12 weeks]
Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment. (1=very much improved, 7=very much worsened)
- Change From Baseline to 12 Weeks in Global Impression of Perceived Difficulties (GIPD) - Participant Rated Version [Baseline, 12 weeks]
The Global Impression of Perceived Difficulties (GIPD) scale is a five-item rating of ADHD-related difficulties. For each item, difficulties during the past week are rated on a 7 point scale (1=normal, not difficult at all; 7= extremely difficult). The GIPD total score is the sum of all subscores (items) and ranges from 5 to 35. Higher scores indicate greater impairment. The scale is completed by the participant.
- Change From Baseline to 12 Weeks in the Children's Depression Rating Scale-Revised (CDRS-R) [Baseline, 12 weeks]
Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale (1 = no symptom difficulties; 5 or 7 = severe clinically significant difficulties) A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression.
- Change From Baseline to 12 Weeks in the Pediatric Anxiety Rating Scale (PARS) [Baseline, 12 weeks]
The Pediatric Anxiety Rating Scale (PARS) is used to rate the severity of anxiety in children and adolescents, ages 6 to 17 years. The total score for the PARS is derived by summing 5 of the 7 severity/impairment/interference items (2,3,5,6,7). The total score ranges from 0 (none) to 25 (extreme severity). Items 1 (overall number of anxiety symptoms) and 4 (overall severity of physical symptoms) are not included in the total score calculation.
- Change From Baseline to 12 Weeks in the Marijuana Craving Questionnaire (MCQ) [Baseline, 12 weeks]
The MCQ is a 12-item self-rated questionnaire to assess cannabis craving with 4 factors: compulsivity (an inability to control marijuana use), emotionality (use of marijuana in anticipation of relief from withdrawal/negative mood), expectancy (anticipation of positive outcomes from smoking marijuana) and purposefulness (intention and planning to use marijuana for positive outcomes). Scores are calculated on a 7-point scale (1=strongly disagree; 7=strongly agree). A separate score is calculated for each factor; scores range from 3-21 each with higher scores indicating greater craving.
- Change From Baseline in Neurocognitive Functioning as Measured at 12 Weeks by a Test Battery: Stop-Signal Task [Baseline, 12 weeks]
Consists of 2 types of trials: go trials and stop trials. Go trials require participants to locate the position of an aircraft displayed to the left or right of a fixation point on a computer screen by pressing a left or right button. In 25% of the go stimili an additional stop stimulus (auditory signal) is presented shortly after the go stimulus. Participant then needs to inhibit their response. By varying the time period between go and stop stimulus, 50% of the trials are inhibited successfully, 50% not. The latency of inhibition is estimated. This task takes about 25 minutes.
- Change From Baseline in Neurocognitive Functioning as Measured at 12 Weeks by a Test Battery: Contingency Task [Baseline, 12 weeks]
For the Contingency Task participants estimate the duration of a time interval of 1 second by pushing a button. Responses that are within a dynamic time interval are being classified as correct. This way, 50 % of the responses are correct, 50% incorrect. Three contingency conditions: neutral, reward and response cost. The performance of this task takes about 15 minutes.
- Change From Baseline in Neurocognitive Functioning as Measured at 12 Weeks by a Test Battery: Time Reproduction Task [Baseline, 12 weeks]
For the Time Reproduction Task participants need to reproduce the duration of a visual stimulus (lightbulb) by pressing a button. The intervals vary between 2 - 20 seconds. The performance of this task takes about 15 minutes.
- C-SSRS Suicidal Ideation By Visit at Week 4: Non-Specific Active Suicidal Thoughts [Week 4]
Solicits suicide-related information with structured questioning. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, intensity of ideation. Suicidal ideation consists of 5 yes/no items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses at a given week are listed.
- C-SSRS Intensity of Ideation (Most Common Ideation Type and Most Severe Ideation Type) By Visit at Week 4 [Week 4]
Participants rate most common and most severe ideation type by frequency (1=<once per week/5=many times/day), duration (1=fleeting/5=>8 times per hour persistent, continuous), controllability (1=easily able to control thoughts/8=no attempt), deterrents to active attempts (1=deterrent definitely stopped you/8=N/A, wish to die only), and reason for ideation (1=completely for attention/revenge/reaction/5=completely to stop the pain). Only items with yes responses at a given week are listed. A participant could have a yes response in more than one item.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis ADHD based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)
-
At least 1.5 standard deviations above the age norm for their diagnostic subtype using published norms for the ADHD Rating Scale-IV-Parent Version
-
Cannabis Abuse or dependence based on the DSM-IV-TR, and using a minimum of 5 joints per week
Exclusion Criteria:
-
Weight under 20 kilograms (kg)
-
Patients at serious suicidal risk
-
Patients with alcohol or drug abuse (other than cannabis)
-
Patients who in the investigator's judgement are likely to need psychotropic medication + psychotherapy apart from atomoxetine
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Den Haag | Netherlands | 2566 ER |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 12382
- B4Z-UT-LYEL
Study Results
Participant Flow
| Recruitment Details | The study was discontinued early owing to difficulties in recruiting the target sample after seven patients had been recruited. Therefore, only disposition, demographic, and safety data are reported. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Period Title: Overall Study | |
| STARTED | 7 |
| COMPLETED | 4 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Overall Participants | 7 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
16.3
(0.95)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
14.3%
|
| Male |
6
85.7%
|
| Race/Ethnicity, Customized (Number) [Number] | |
| Caucasian |
5
71.4%
|
| East Asian |
1
14.3%
|
| West Asian |
1
14.3%
|
| Region of Enrollment (participants) [Number] | |
| Netherlands |
7
100%
|
| Columbia Suicide Rating Scale (C-SSRS) Suicidal Behavior (Number) [Number] | |
| Aborted Attempt |
1
14.3%
|
| Non-Suicidal Self Injurious Behavior |
2
28.6%
|
| Presence of Suicidal Behavior |
1
14.3%
|
| Actual Attempt |
1
14.3%
|
Outcome Measures
| Title | Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale-IV-Parent Version: Investigator Scored Total Score at 12 Weeks |
|---|---|
| Description | Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. Higher scores indicate greater impairment. The scale is scored by an investigator while interviewing the parent. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Clinical Global Impression-ADHD-Improvement (CGI-ADHD-I) at 12 Weeks |
|---|---|
| Description | Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment. (1=very much improved, 7=very much worsened) |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Change From Baseline to 12 Weeks in Global Impression of Perceived Difficulties (GIPD) - Participant Rated Version |
|---|---|
| Description | The Global Impression of Perceived Difficulties (GIPD) scale is a five-item rating of ADHD-related difficulties. For each item, difficulties during the past week are rated on a 7 point scale (1=normal, not difficult at all; 7= extremely difficult). The GIPD total score is the sum of all subscores (items) and ranges from 5 to 35. Higher scores indicate greater impairment. The scale is completed by the participant. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Change From Baseline to 12 Weeks in the Children's Depression Rating Scale-Revised (CDRS-R) |
|---|---|
| Description | Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale (1 = no symptom difficulties; 5 or 7 = severe clinically significant difficulties) A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Change From Baseline to 12 Weeks in the Pediatric Anxiety Rating Scale (PARS) |
|---|---|
| Description | The Pediatric Anxiety Rating Scale (PARS) is used to rate the severity of anxiety in children and adolescents, ages 6 to 17 years. The total score for the PARS is derived by summing 5 of the 7 severity/impairment/interference items (2,3,5,6,7). The total score ranges from 0 (none) to 25 (extreme severity). Items 1 (overall number of anxiety symptoms) and 4 (overall severity of physical symptoms) are not included in the total score calculation. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Change From Baseline to 12 Weeks in the Marijuana Craving Questionnaire (MCQ) |
|---|---|
| Description | The MCQ is a 12-item self-rated questionnaire to assess cannabis craving with 4 factors: compulsivity (an inability to control marijuana use), emotionality (use of marijuana in anticipation of relief from withdrawal/negative mood), expectancy (anticipation of positive outcomes from smoking marijuana) and purposefulness (intention and planning to use marijuana for positive outcomes). Scores are calculated on a 7-point scale (1=strongly disagree; 7=strongly agree). A separate score is calculated for each factor; scores range from 3-21 each with higher scores indicating greater craving. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Change From Baseline in Neurocognitive Functioning as Measured at 12 Weeks by a Test Battery: Stop-Signal Task |
|---|---|
| Description | Consists of 2 types of trials: go trials and stop trials. Go trials require participants to locate the position of an aircraft displayed to the left or right of a fixation point on a computer screen by pressing a left or right button. In 25% of the go stimili an additional stop stimulus (auditory signal) is presented shortly after the go stimulus. Participant then needs to inhibit their response. By varying the time period between go and stop stimulus, 50% of the trials are inhibited successfully, 50% not. The latency of inhibition is estimated. This task takes about 25 minutes. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Change From Baseline in Neurocognitive Functioning as Measured at 12 Weeks by a Test Battery: Contingency Task |
|---|---|
| Description | For the Contingency Task participants estimate the duration of a time interval of 1 second by pushing a button. Responses that are within a dynamic time interval are being classified as correct. This way, 50 % of the responses are correct, 50% incorrect. Three contingency conditions: neutral, reward and response cost. The performance of this task takes about 15 minutes. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | Change From Baseline in Neurocognitive Functioning as Measured at 12 Weeks by a Test Battery: Time Reproduction Task |
|---|---|
| Description | For the Time Reproduction Task participants need to reproduce the duration of a visual stimulus (lightbulb) by pressing a button. The intervals vary between 2 - 20 seconds. The performance of this task takes about 15 minutes. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 0 |
| Title | C-SSRS Suicidal Ideation By Visit at Week 4: Non-Specific Active Suicidal Thoughts |
|---|---|
| Description | Solicits suicide-related information with structured questioning. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, intensity of ideation. Suicidal ideation consists of 5 yes/no items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses at a given week are listed. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 7 |
| Number [Participants] |
1
14.3%
|
| Title | C-SSRS Intensity of Ideation (Most Common Ideation Type and Most Severe Ideation Type) By Visit at Week 4 |
|---|---|
| Description | Participants rate most common and most severe ideation type by frequency (1=<once per week/5=many times/day), duration (1=fleeting/5=>8 times per hour persistent, continuous), controllability (1=easily able to control thoughts/8=no attempt), deterrents to active attempts (1=deterrent definitely stopped you/8=N/A, wish to die only), and reason for ideation (1=completely for attention/revenge/reaction/5=completely to stop the pain). Only items with yes responses at a given week are listed. A participant could have a yes response in more than one item. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| It was planned to use the full analysis set (FAS) for the efficacy and safety analyses, which included data from all participants who received at least one dose of atomoxetine and had at least one post-baseline assessment. |
| Arm/Group Title | Atomoxetine |
|---|---|
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. |
| Measure Participants | 7 |
| Frequency (Most Common) Once a Week |
1
14.3%
|
| Frequency (Most Severe) Once a Week |
1
14.3%
|
| Duration (Most Common) Fleeting |
1
14.3%
|
| Duration (Most Severe) Fleeting |
1
14.3%
|
| Control (Most Common) Little Diffficulty |
1
14.3%
|
| Control (Most Severe) Little Diffficulty |
1
14.3%
|
| Deterrent (Most Common) Uncertain It Stopped You |
1
14.3%
|
| Deterrent (Most Severe) Uncertain it Stopped You |
1
14.3%
|
| Reasons (Most Common) Mostly to Get Attention |
1
14.3%
|
| Reasons (Most Severe) Mostly to Get Attention |
1
14.3%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Atomoxetine | |
| Arm/Group Description | 0.5 milligrams per kilogram (mg/kg) daily for 1 week followed by 1.2 mg/kg daily for 11 weeks, orally, capsules. | |
All Cause Mortality |
||
| Atomoxetine | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Atomoxetine | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Atomoxetine | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | |
| Gastrointestinal disorders | ||
| Dry mouth | 1/7 (14.3%) | 1 |
| Nausea | 5/7 (71.4%) | 8 |
| Vomiting | 1/7 (14.3%) | 1 |
| General disorders | ||
| Asthenia | 1/7 (14.3%) | 1 |
| Irritability | 2/7 (28.6%) | 2 |
| Malaise | 1/7 (14.3%) | 1 |
| Infections and infestations | ||
| Influenza | 1/7 (14.3%) | 1 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 1/7 (14.3%) | 1 |
| Nervous system disorders | ||
| Disturbance in attention | 1/7 (14.3%) | 1 |
| Dizziness | 1/7 (14.3%) | 1 |
| Headache | 2/7 (28.6%) | 2 |
| Psychiatric disorders | ||
| Decreased activity | 1/7 (14.3%) | 1 |
| Depression | 1/7 (14.3%) | 1 |
| Stress | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Hyperhidrosis | 1/7 (14.3%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
- 12382
- B4Z-UT-LYEL