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Quetiapine and Concerta in the Treatment for ADHD and Aggressive Behavior.

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ClinicalTrials.gov Identifier: NCT00550147
Recruitment Status : Completed
First Posted : October 29, 2007
Results First Posted : May 13, 2015
Last Update Posted : May 13, 2015
Sponsor:
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Attention Deficit Disorder With Hyperactivity
Interventions Drug: Oros Methylphenidate
Drug: quetiapine
Enrollment 30
Recruitment Details Subjects were recruited during the time period 2004-2005, using flyers and letters sent to local schools, clinics, and community agencies, as well as from referrals to the site at which the study was conducted.
Pre-assignment Details All eligible subjects were assigned to the first phase of treatment (Oros MPH alone).
Arm/Group Title OROS Methylphenidate and Quetiapine
Hide Arm/Group Description This is the Baseline Visit, immediately after enrollment and prior to taking any medication. All enrolled subjects start taking OROS methylphenidate until Visit 5. At visit 5, if there is significant improvement (decrease in aggressive symptoms), then subject is discontinued from the study. If there is not significant improvement, then subject continues in study and begins taking OROS methylphenidate plus quetiapine. 24 of 30 subjects entered the OROS methylphenidate and quetiapine arm. 4 subjects made significant improvement at visit 5 and were discontinued from the study; 2 subjects were withdrawn from the study prior to visit 5. Therefore, 6 of 30 subjects did not enter the OROS methylphenidate and quetiapine arm. Only 24 of 30 subjects entered this arm. Visit 10 is measured at the end of OROS MPH+Quetiapine treatment
Period Title: OROS Methylphenidate Monotherapy
Started 30
Completed 24
Not Completed 6
Reason Not Completed
significant improvement at visit 5             4
Withdrawal by Subject             2
Period Title: Quetiapine Addition Treatment Period
Started 24
Completed 18
Not Completed 6
Reason Not Completed
Adverse Event             3
Noncompliance             2
Moved out of state             1
Arm/Group Title OROS Methylphenidate and Quetiapine
Hide Arm/Group Description All enrolled subjects start taking OROS methylphenidate. At visit 5, if there is significant improvement (decrease in aggressive symptoms), then subject is discontinued from the study. If there is not significant improvement, then subject continues in study and begins taking OROS methylphenidate plus quetiapine. Therefore enters the OROS methylphenidate and quetiapine arm. 24 of 30 subjects entered the OROS methylphenidate and quetiapine arm. 4 subjects made significant improvement at visit 5 and were discontinued from the study, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. 2 subjects were withdrawn from the study prior to visit 5, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. Therefore, 6 of 30 subjects did not enter the OROS methylphenidate and quetiapine arm. Only 24 of 30 subjects entered this arm.
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
<=18 years
30
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
13.2  (1.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
9
  30.0%
Male
21
  70.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
1.Primary Outcome
Title RAAPP: Rating of Aggression Against People and/or Property Scale
Hide Description The RAAPP is a global rating scale of aggression that is completed by a clinician based on interview and observation data. It is scored from 1 (no aggression reported) to 5 (intolerable behavior).
Time Frame See Arm/Group - Repeated Measures
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).
Arm/Group Title Baseline Visit 5 - MPH Monotherapy - Week 4 Visit 10 - MPH+Quetiapine - Week 13
Hide Arm/Group Description:
Baseline score at study entry
Score following treatment with MPH monotherapy after Week 4
Score following treatment with combined MPH and quetiapine after Week 13
Overall Number of Participants Analyzed 24 24 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
4.3  (0.4) 3.2  (0.6) 2.0  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Visit 5 - MPH Monotherapy - Week 4, Visit 10 - MPH+Quetiapine - Week 13
Comments This was a repeated-measures analysis, using a single group of subjects who were administered quetiapine in addition to OROS mph. See Kronenberger et al. (2007, Journal of Child and Adolescent Psychopharmacology) for additional information.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test (comparing augmentation period start score with end score), 23 df. Value is Visit 10 score minus Visit 5 score (null hypothesis=0).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.125
Confidence Interval (2-Sided) 95%
-1.52 to -0.72
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1933
Estimation Comments This was a comparison of pre-post change in a single group, with treatment administered open-label.
2.Secondary Outcome
Title CGI-S: Clinical Global Improvement Scale
Hide Description The CGI-S is a 1-7 investigator rating of overall severity of target behavioral symptoms, which will be completed at each visit as a secondary efficacy measure of global behavioral functioning. A score of 1 indicates "normal, not ill at all" and a score of 7 indicates "among the most extremely ill patients".
Time Frame See Arm/Group - Repeated Measures
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).
Arm/Group Title Baseline Visit 5 - MPH Monotherapy - Week 4 Visit 10 - MPH + Quetiapine - Week 13
Hide Arm/Group Description:
Baseline scores at study entry
Score following treatment with MPH monotherapy after Week 4
Score following treatment with MPH+quetiapine after Week 13
Overall Number of Participants Analyzed 24 24 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
5.3  (0.6) 4.1  (0.8) 2.8  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Visit 5 - MPH Monotherapy - Week 4, Visit 10 - MPH + Quetiapine - Week 13
Comments This was a repeated-measures analysis, using a single group of subjects who were administered quetiapine in addition to OROS mph. Results reported here are for the augmentation period (Visit 5-10). See Kronenberger et al. (2007, Journal of Child and Adolescent Psychopharmacology) for additional information.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test (comparing augmentation period start score with end score), 23 df. Value is Visit 10 score minus Visit 5 score (null hypothesis=0).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.33
Confidence Interval 95%
-1.75 to -0.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2056
Estimation Comments This was a comparison of pre-post change in a single group, with treatment administered open-label.
3.Secondary Outcome
Title Modified Overt Aggression Scale (MOAS)
Hide Description The Modified Overt Aggression Scale (MOAS) is a clinician-rated scale of aggressive outbursts experienced in the past week. Weightings are assigned for severity and frequency of aggression. MOAS total severity score will be completed as a secondary efficacy measure of aggressive behavior. The range for the MOAS is 0-235. A score of 0 indicates "no aggression" and a score of 235 indicates "the most severe and frequent aggressive outbursts".
Time Frame See arm/group - repeated measures
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).
Arm/Group Title Baseline Visit 5 - MPH Monotherapy - Week 4 Visit 10 - MPH + Quetiapine - Week 13
Hide Arm/Group Description:
Baseline scores at study entry
Score following treatment with MPH monotherapy after Week 4
Score following treatment with MPH+quetiapine after Week 13
Overall Number of Participants Analyzed 24 24 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
229.0  (194.3) 73.7  (57.9) 26.3  (33.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Visit 5 - MPH Monotherapy - Week 4, Visit 10 - MPH + Quetiapine - Week 13
Comments This was a repeated-measures analysis, using a single group of subjects who were administered quetiapine in addition to OROS mph. Results reported here are for the augmentation period (Visit 5-10). See Kronenberger et al. (2007, Journal of Child and Adolescent Psychopharmacology) for additional information.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test (comparing augmentation period start score with end score), 23 df. Value is Visit 10 score minus Visit 5 score (null hypothesis=0).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -47.3
Confidence Interval 95%
-74.3 to -20.2
Parameter Dispersion
Type: Standard Error of the mean
Value: 13.06
Estimation Comments This was a comparison of pre-post change in a single group, with treatment administered open-label.
4.Secondary Outcome
Title Swanson, Nolan and Pelham IV (SNAP-IV) Oppositional-Defiant Disorder Subscale
Hide Description The Swanson, Nolan and Pelham (SNAP-IV) is a 90-item, parent-completed questionnaire consisting of symptoms of ADHD, aggression, depression, and mania. Parents rate each item from 0(not at all) to 3 (very much) based on their child's behavior during the past week. The scores from the Oppositional-Defiant Disorder section of this questionnaire will be used as secondary efficacy measures of parent-reported aggressive behavior. These scores range from 0-24.
Time Frame See arm/group - repeated measures analysis
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).
Arm/Group Title Baseline Visit 5 - MPH Monotherapy - Week 4 Visit 10 - MPH+Quetiapine - Week 13
Hide Arm/Group Description:
Baseline scores at Study Entry
Score following treatment with MPH Monotherapy after Week 4
Score following treatment with MPH+quetiapine after Week 13
Overall Number of Participants Analyzed 24 24 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
19.0  (4.1) 14.5  (6.2) 10.3  (6.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Visit 5 - MPH Monotherapy - Week 4, Visit 10 - MPH+Quetiapine - Week 13
Comments This was a repeated-measures analysis, using a single group of subjects who were administered quetiapine in addition to OROS mph. Results reported here are for the augmentation period (Visit 5-10). See Kronenberger et al. (2007, Journal of Child and Adolescent Psychopharmacology) for additional information.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test (comparing augmentation period start score with end score), 23 df. Value is Visit 10 score minus Visit 5 score (null hypothesis=0).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.17
Confidence Interval (2-Sided) 95%
-7.04 to -1.29
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.39
Estimation Comments This was a comparison of pre-post change in a single group, with treatment administered open-label.
5.Secondary Outcome
Title Attention Deficit/Hyperactivity Disorder Rating Scale -IV- Parent Version (ADHDRS-IV-Parent Version)
Hide Description The Attention Deficit/Hyperactivity Disorder Rating Scale -IV- Parent Version (ADHDRS-IV-Parent:Inv) (Faries, Yalcin, Harder, & Heiligenstein, 2001) is an interviewer-administered semi structured interview with the parent, focusing on the 18 DSM-IV symptoms. Ratings are made on a 0 (never or rarely) to 3 (very often) scale. The range of the ADHDRS-IV is 0-54. A zero (0) scores indicates no ADHD symptoms and 54 indicates most severe ADHD symptoms. The ADHDRS-IV-Parent:Inv provides an overall severity score, symptom count, and ADHD diagnosis for the child.
Time Frame See Arm/Group - repeated measures
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).
Arm/Group Title Baseline Visit 5 - MPH Monotherapy - Week 4 Visit 10 - MPH+Quetiapine - Week 13
Hide Arm/Group Description:
Baseline scores at study entry
Score following treatment with MPH monotherapy after week 4
Score following treatment with MPH+Quetiapine after Week 13
Overall Number of Participants Analyzed 24 24 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
45.7  (5.8) 32.7  (10.8) 19.4  (9.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Visit 5 - MPH Monotherapy - Week 4, Visit 10 - MPH+Quetiapine - Week 13
Comments This was a repeated-measures analysis, using a single group of subjects who were administered quetiapine in addition to OROS mph. Results reported here are for the augmentation period (Visit 5-10). See Kronenberger et al. (2007, Journal of Child and Adolescent Psychopharmacology) for additional information.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments Paired t-test (comparing augmentation period start score with end score), 23 df. Value is Visit 10 score minus Visit 5 score (null hypothesis=0).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.29
Confidence Interval 95%
-17.76 to -8.82
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.16
Estimation Comments This was a comparison of pre-post change in a single group, with treatment administered open-label.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OROS Methylphenidate and Quetiapine
Hide Arm/Group Description All enrolled subjects start taking OROS methylphenidate. At visit 5, if there is significant improvement (decrease in aggressive symptoms), then subject is discontinued from the study. If there is not significant improvement, then subject continues in study and begins taking OROS methylphenidate plus quetiapine. Therefore enters the OROS methylphenidate and quetiapine arm. 24 of 30 subjects entered the OROS methylphenidate and quetiapine arm. 4 subjects made significant improvement at visit 5 and were discontinued from the study, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. 2 subjects were withdrawn from the study prior to visit 5, and, therefore, did not enter the OROS methylphenidate and quetiapine arm. Therefore, 6 of 30 subjects did not enter the OROS methylphenidate and quetiapine arm. Only 24 of 30 subjects entered this arm.
All-Cause Mortality
OROS Methylphenidate and Quetiapine
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
OROS Methylphenidate and Quetiapine
Affected / at Risk (%) # Events
Total   0/24 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
OROS Methylphenidate and Quetiapine
Affected / at Risk (%) # Events
Total   23/24 (95.83%)    
Gastrointestinal disorders   
stomachache/nausea *  7/24 (29.17%)  7
vomiting *  4/24 (16.67%)  4
General disorders   
headache *  4/24 (16.67%)  4
fatigue/sedation *  12/24 (50.00%)  12
difficulty sleeping *  7/24 (29.17%)  7
flu-like syndrome *  5/24 (20.83%)  5
lability/irritability *  4/24 (16.67%)  4
dizziness *  3/24 (12.50%)  3
Metabolism and nutrition disorders   
reduced appetite *  4/24 (16.67%)  4
Respiratory, thoracic and mediastinal disorders   
repiratory illness *  9/24 (37.50%)  9
Skin and subcutaneous tissue disorders   
bruises/cuts/bumps *  3/24 (12.50%)  3
*
Indicates events were collected by non-systematic assessment
There were no unanticipated limitations/caveats. All of the typical caveats of open-label studies apply: As a result, bias, placebo effects, demand characteristics, and other non-treatment related effects may have contributed to results.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: David W. Dunn, MD
Organization: Indiana University School of Medicine
Phone: 317-944-8162
Responsible Party: Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier: NCT00550147     History of Changes
Obsolete Identifiers: NCT00198211
Other Study ID Numbers: 0307-31 (IRB#)
First Submitted: October 25, 2007
First Posted: October 29, 2007
Results First Submitted: April 3, 2009
Results First Posted: May 13, 2015
Last Update Posted: May 13, 2015