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Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1)

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ClinicalTrials.gov Identifier: NCT00429273
Recruitment Status : Completed
First Posted : January 31, 2007
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
James McCracken, University of California, Los Angeles

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Attention Deficit Disorder With Hyperactivity
Interventions Drug: Guanfacine
Drug: Methylphenidate (MPH)
Enrollment 212

Recruitment Details  
Pre-assignment Details

212 randomized (deemed eligible and enrolled). 71 randomized to Group 1: 3 dropped prior to receiving drug; thus 68 started drug.

70 randomized to Group 2: 1 dropped before receiving drug; thus 69 started drug.

71 randomized to Group 3:1 dropped before receiving drug; thus 70 started drug.

Arm/Group Title Group 1: Guan-Guan+Placebo Group 2: Placebo-Placebo+DMPH Group 3: Guan-Guan+DMPH
Hide Arm/Group Description weeks 1-4: Guanfacine weeks 5-8: Guanfacine+Placebo weeks 1-4: Placebo weeks 5-8: Placebo+DMPH weeks 1-4: Guanfacine weeks 5-8: Guanfacine+DMPH (comb)
Period Title: Overall Study
Started 68 69 70
Completed 60 61 61
Not Completed 8 8 9
Reason Not Completed
Lost to Follow-up             1             2             2
Physician Decision             6             5             5
Adverse Event             1             1             2
Arm/Group Title Group 1: Guan-Guan+Placebo Group 2: Placebo-Placebo+DMPH Group 3: Guan-Guan+DMPH (Comb) Total
Hide Arm/Group Description weeks 1-4: Guanfacine weeks 5-8: Guanfacine +Placebo weeks 1-4: Placebo weeks 5-8: Placebo+DMPH weeks 1-4: Guanfacine weeks 5-8: Guanfacine+DMPH (comb) Total of all reporting groups
Overall Number of Baseline Participants 68 69 70 207
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 68 participants 69 participants 70 participants 207 participants
10.1  (2.1) 10.1  (2.0) 9.9  (2.2) 10.0  (2.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 69 participants 70 participants 207 participants
Female
23
  33.8%
23
  33.3%
19
  27.1%
65
  31.4%
Male
45
  66.2%
46
  66.7%
51
  72.9%
142
  68.6%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 69 participants 70 participants 207 participants
White
51
  75.0%
51
  73.9%
41
  58.6%
143
  69.1%
African American
7
  10.3%
10
  14.5%
19
  27.1%
36
  17.4%
Asian, Pacific Islander
7
  10.3%
4
   5.8%
5
   7.1%
16
   7.7%
Other
3
   4.4%
4
   5.8%
5
   7.1%
12
   5.8%
Hispanic
16
  23.5%
10
  14.5%
18
  25.7%
44
  21.3%
[1]
Measure Analysis Population Description: of the 212 participants randomized, 207 received at least one dose of study drug and form the safety and intent-to-treat samples.
1.Primary Outcome
Title ADHD IV Rating Scale (Attention Deficit Hyperactivity Disorder Rating Scale)
Hide Description

The primary clinical efficacy variable for treatment was the ADHD-RS-IV Total Score and two sub-scales (Inattentive and Hyperactive-Impulsive ).

The rating scale has 18 questions with answer options: None (0), Mild (1), Moderate (2) and Severe (3).

Scores are obtained by summing each item; The higher the score, the worse the outcome.

Total score range: 0-54 Total Inattentive score range: 0-27 Total Hyperactive/Impulsive score range: 0-27

Time Frame Measured at baseline Week 4 and Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Every contrast includes estimates of maturation/time trend and the within subject covariance structure based on all participants using full information maximum likelihood estimation.
Arm/Group Title Estimated Difference Between Guan and Placebo Estimated Difference Between DMPH and Placebo Estimated Difference Between Placebo and Combo
Hide Arm/Group Description:
Contrasts based on all observations of patients treated with guam and all patients on placebo controlling for time effects. For placebo this included patients in the guan-guan arm at baseline, the guan-combo arm at baseline, and the placebo-DMPH arm at baseline and 4 weeks, while the estimates for guan are based on the guan-guan arm both at 4 weeks and 8 weeks, and the guan-combo arm at 4 weeks only. Participant specific effects and time effects are controlled for based on estimates from all participants and all time points.
Contrasts based on all observations of patients treated with dmph and all patients on placebo controlling for time effects. For placebo this included patients in the guan-guan arm at baseline, the guan-combo arm at baseline, and the placebo-DMPH arm at baseline and 4 weeks, while the estimates for DMPH are based on the placebo-guan arm at 8 weeks. Participant specific effects and time effects are controlled for based on estimates from all participants and all time points.
Contrasts based on all observations of patients treated with combo and all patients on placebo controlling for time effects. For placebo this included patients in the guan-guan arm at baseline, the guan-combo arm at baseline, and the placebo-DMPH arm at baseline and 4 weeks, while the estimates for DMPH are based on the guan-combo arm at 8 weeks. Participant specific effects and time effects are controlled for based on estimates from all participants and all time points.
Overall Number of Participants Analyzed 207 207 207
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Total ADHD-RS Score -7.77  (1.70) -7.99  (1.22) -10.66  (1.99)
Inattentive Subscale -4.14  (0.99) -4.10  (0.71) -5.89  (1.15)
Hyperactive Impulsive Subscale -3.73  (0.92) -4.0  (0.69) -5.10  (1.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estimated Difference Between Guan and Placebo, Estimated Difference Between DMPH and Placebo, Estimated Difference Between Placebo and Combo
Comments Analyses are based on a generalized linear mixed model (GLMM) modelling the effects of the medication when calibrated to optimal dosage and controlling for time effects and within-subject effects. The design is a combined within-between subject design, where each participant is exposed to, and provides information about multiple tx modalities.
Type of Statistical Test Other
Comments Test for differences in treatment outcomes between three different tx
Statistical Test of Hypothesis P-Value <.01
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter F-Value for variance component
Estimated Value 18.90
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1: Guan-Guan+Placebo Group 2: Placebo-Placebo+DMPH Group 3: Guan-Guan+DMPH
Hide Arm/Group Description week 1-4: Guanfacine weeks 5-8: Guanfacine+Placebo week 1-4: Placebo week 5-8: Placebo+DMPH week 1-4: Guanfacine week 5-8: Guanfacine+DMPH (comb)
All-Cause Mortality
Group 1: Guan-Guan+Placebo Group 2: Placebo-Placebo+DMPH Group 3: Guan-Guan+DMPH
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/68 (0.00%)      0/69 (0.00%)      0/70 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Group 1: Guan-Guan+Placebo Group 2: Placebo-Placebo+DMPH Group 3: Guan-Guan+DMPH
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/68 (0.00%)      0/69 (0.00%)      0/70 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1: Guan-Guan+Placebo Group 2: Placebo-Placebo+DMPH Group 3: Guan-Guan+DMPH
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   66/68 (97.06%)      66/69 (95.65%)      69/70 (98.57%)    
Gastrointestinal disorders       
Abdominal Pain Upper *  11/68 (16.18%)  11 10/69 (14.49%)  10 10/70 (14.29%)  10
Abdominal Pain *  19/68 (27.94%)  19 18/69 (26.09%)  18 16/70 (22.86%)  16
General disorders       
Insomnia *  18/68 (26.47%)  18 20/69 (28.99%)  20 24/70 (34.29%)  24
Lethargy *  23/68 (33.82%)  23 9/69 (13.04%)  9 16/70 (22.86%)  16
Fatigue *  22/68 (32.35%)  22 5/69 (7.25%)  5 12/70 (17.14%)  12
Metabolism and nutrition disorders       
Decreased Appetite *  15/68 (22.06%)  15 31/69 (44.93%)  31 25/70 (35.71%)  25
Psychiatric disorders       
Headache *  34/68 (50.00%)  34 23/69 (33.33%)  23 23/70 (32.86%)  23
Irritability *  15/68 (22.06%)  15 12/69 (17.39%)  12 18/70 (25.71%)  18
Sedation *  12/68 (17.65%)  12 4/69 (5.80%)  4 16/70 (22.86%)  16
Somnolence *  16/68 (23.53%)  16 3/69 (4.35%)  3 15/70 (21.43%)  15
Affect Lability *  7/68 (10.29%)  7 14/69 (20.29%)  14 8/70 (11.43%)  8
Vascular disorders       
Dizziness *  8/68 (11.76%)  8 6/69 (8.70%)  6 7/70 (10.00%)  7
*
Indicates events were collected by non-systematic assessment
Larger group sizes would enable more conclusive tests of treatment differences; Study design began with guanfacine first and addition of a stimulant second, making difficult to compare to those study designs adding guanfacine to ongoing stimulants.
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: James T. McCracken, M.D.
Organization: University of California, Los Angeles
Phone: 310-825-0470
Responsible Party: James McCracken, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00429273     History of Changes
Other Study ID Numbers: P50MH077248-01 ( U.S. NIH Grant/Contract )
P50MH077248-01 ( U.S. NIH Grant/Contract )
DDTR B2-NDH
10-000453 ( Other Identifier: Office for Protection of Human Subjects )
First Submitted: January 29, 2007
First Posted: January 31, 2007
Results First Submitted: January 18, 2017
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017