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Effects of Atomoxetine on Brain Activation During Attention & Reading Tasks in Participants With ADHD & Comorbid Dyslexia

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ClinicalTrials.gov Identifier: NCT00716274
Recruitment Status : Completed
First Posted : July 16, 2008
Results First Posted : February 7, 2018
Last Update Posted : May 7, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions: Attention Deficit Hyperactivity Disorder
Dyslexia
Interventions: Drug: Atomoxetine
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized to either atomoxetine or placebo during study period II. Placebo participants were then assigned to atomoxetine in study period III. Atomoxetine participants were re-randomized to atomoxetine or placebo in study period III. Participants assigned to the healthy control group did not receive any study drug.

Reporting Groups
  Description
Atomoxetine Atomoxetine (ATX) 1.0 to 1.4 milligram/kilogram/day (mg/kg/day) was administered orally once daily in the morning for 16 weeks, during study period II, (SP II). All eligible participants who received atomoxetine during study period II and completed that period were re-randomized to atomoxetine or placebo in study period III (SP III).
Placebo Placebo (PLA) was packaged in the same way as active comparator to enforce double-blind study design. Placebo was given orally, daily for 16 weeks during SP II. All eligible participants who received placebo during SP II and completed that period were assigned atomoxetine in SP III.
ATX/ATX These participants were randomized to atomoxetine in SP II and were re-randomized to atomoxetine in SP III. Atomoxetine was dosed orally once-daily in the morning 0.5 mg/kg/day for 3 days and then titrated up to a dose between 1.2 and 1.4 mg/kg/day.
ATX/PLA These participants were randomized to atomoxetine in SP II and were re-randomized to placebo in SP III. Atomoxetine was dosed orally once-daily in the morning 0.5 mg/kg/day for 3 days and then titrated up to a dose between 1.2 and 1.4 mg/kg/day.
PLA/ATX These participants were randomized to placebo in SP II and were assigned to atomoxetine in SP III. Atomoxetine was dosed orally once-daily in the morning 0.5 mg/kg/day for 3 days and then titrated up to a dose between 1.2 and 1.4 mg/kg/day.
Healthy Participants Healthy Participants: Participants were evaluated to confirm that they did not meet criteria for Attention Deficit Hyperactivity Disorder (ADHD) or dyslexia. They received no treatment during the study.

Participant Flow for 2 periods

Period 1:   Study Period II (16-Weeks)
    Atomoxetine   Placebo   ATX/ATX   ATX/PLA   PLA/ATX   Healthy Participants
STARTED   45   44   0   0   0   21 
COMPLETED   36   35   0   0   0   19 
NOT COMPLETED   9   9   0   0   0   2 
Entry Criteria Not Met                2                0                0                0                0                0 
Protocol Violation                0                3                0                0                0                1 
Withdrawal by Subject                1                0                0                0                0                0 
Physician Decision                3                1                0                0                0                1 
Parent/Caregiver Decision                3                3                0                0                0                0 
Lost to Follow-up                0                2                0                0                0                0 

Period 2:   Study Period III (16-Weeks)
    Atomoxetine   Placebo   ATX/ATX   ATX/PLA   PLA/ATX   Healthy Participants
STARTED   0 [1]   0 [1]   18 [1]   18 [1]   35 [1]   19 [1] 
COMPLETED   0   0   16   17   32   19 
NOT COMPLETED   0   0   2   1   3   0 
Withdrawal by Subject                0                0                2                0                0                0 
Physician Decision                0                0                0                0                1                0 
Parent Caregiver Decision                0                0                0                1                1                0 
Adverse Event                0                0                0                0                1                0 
[1] Participants were assessed for maintenance of benefit after discontinuation of atomoxetine.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Atomoxetine Atomoxetine 1.0 to 1.4 mg/kg/day was administered orally once daily in the morning for 16 weeks, during SP II. All eligible participants who received atomoxetine during SP II and completed that period were re-randomized to atomoxetine or placebo in SP III.
Placebo Placebo was packaged in the same way as active comparator to enforce double-blind study design. Placebo was given orally, daily for 16 weeks during SP II. All eligible participants who received placebo during SP II and completed that period were assigned atomoxetine in SP III.
Healthy Participants Healthy Participants: Participants were evaluated to confirm that they did not meet criteria for ADHD or dyslexia. They received no treatment during the study.
Total Total of all reporting groups

Baseline Measures
   Atomoxetine   Placebo   Healthy Participants   Total 
Overall Participants Analyzed 
[Units: Participants]
 45   44   21   110 
Age 
[Units: Years]
Mean (Standard Deviation)
 12.2  (1.89)   12.1  (1.90)   12.4  (2.05)   12.20  (1.92) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female   18   17   13   48 
Male   27   27   8   62 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
       
Hispanic or Latino   6   2   4   12 
Not Hispanic or Latino   39   42   17   98 
Unknown or Not Reported   0   0   0   0 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
       
American Indian or Alaska Native   0   0   0   0 
Asian   2   0   0   2 
Native Hawaiian or Other Pacific Islander   0   0   0   0 
Black or African American   4   13   5   22 
White   33   29   12   74 
More than one race   0   0   0   0 
Unknown or Not Reported   6   2   4   12 
Region of Enrollment 
[Units: Participants]
Count of Participants
       
United States   45   44   21   110 


  Outcome Measures

1.  Primary:   Change From Baseline to Endpoint in Woodcock Johnson Tests of Achievement (WJ III) Word Attack Total Score in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 Weeks ]

2.  Primary:   Change From Baseline to Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version (ADHDRS) Total Score in the ADHD or ADHD + Dyslexia   [ Time Frame: Baseline, 16 weeks ]

3.  Secondary:   Change From Baseline to Endpoint in Basic Reading Skills Cluster WJ III in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 Weeks ]

4.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia   [ Time Frame: Baseline, 16 Weeks ]

5.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 Weeks ]

6.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With ADHD + Dyslexia   [ Time Frame: Baseline, 16 Weeks ]

7.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Test Scores in Participants With ADHD Alone   [ Time Frame: Baseline, 16 Weeks ]

8.  Secondary:   Change From Baseline to Endpoint in Comprehensive Test of Phonological Processing (CTOPP) Composite Scores in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 weeks ]

9.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Score in Participants With ADHD + Dyslexia   [ Time Frame: Baseline, 16 weeks ]

10.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Score in Participants With ADHD Alone   [ Time Frame: Baseline, 16 weeks ]

11.  Secondary:   Change From Baseline to Endpoint in Gray Oral Reading Tests-4 (GORT-4) in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 weeks ]

12.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With ADHD + Dyslexia   [ Time Frame: Baseline, 16 weeks ]

13.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With ADHD Alone   [ Time Frame: Baseline, 16 weeks ]

14.  Secondary:   Change From Baseline to Endpoint Test of Word Reading Efficiency (TOWRE) Total Score in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 Weeks ]

15.  Secondary:   Change From Baseline to Endpoint in TOWRE Total Score in Participants With ADHD or ADHD + Dyslexia   [ Time Frame: Baseline, 16 Weeks ]

16.  Secondary:   Change From Baseline to Endpoint in Working Memory Test Battery for Children (WMTB-C) in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 Weeks ]

17.  Secondary:   Change From Baseline to Endpoint WMTB-C in Participants With ADHD + Dyslexia   [ Time Frame: Baseline, 16 Weeks ]

18.  Secondary:   Change From Baseline to Endpoint WMTB-C in Participants With ADHD Alone   [ Time Frame: Baseline, 16 Weeks ]

19.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 Weeks ]

20.  Secondary:   Change From Baseline to Endpoint in ADHDRS-IV Total Score in Participants With Dyslexia Alone   [ Time Frame: Baseline, 16 Weeks ]

21.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Participants With Dyslexia Alone   [ Time Frame: Baseline, 32 Weeks ]

22.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD + Dyslexia   [ Time Frame: Baseline, 32 Weeks ]

23.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD Alone   [ Time Frame: Baseline, 32 Weeks ]

24.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With Dyslexia Alone   [ Time Frame: Baseline, 32 Weeks ]

25.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD + Dyslexia   [ Time Frame: Baseline, 32 Weeks ]

26.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD Alone   [ Time Frame: Baseline, 32 Weeks ]

27.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With Dyslexia Alone   [ Time Frame: Baseline, 32 Weeks ]

28.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With ADHD + Dyslexia   [ Time Frame: Baseline, 32 Weeks ]

29.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With ADHD Alone   [ Time Frame: Baseline, 32 Weeks ]

30.  Secondary:   Change From Baseline to Endpoint in Participants in TOWRE Total Score With Dyslexia Alone   [ Time Frame: Baseline, 32 Weeks ]

31.  Secondary:   Change From Baseline to Endpoint in Participants in TOWRE Total Score With ADHD or ADHD + Dyslexia   [ Time Frame: Baseline, 32 Weeks ]

32.  Secondary:   Change From Baseline to Endpoint in Participants in WMTB-C With Dyslexia Alone   [ Time Frame: Baseline, 32 Weeks ]

33.  Secondary:   Change From Baseline to Endpoint in Participants in WMTB-C With ADHD + Dyslexia   [ Time Frame: Baseline, 32 Weeks ]

34.  Secondary:   Change From Baseline to Endpoint in Participants in WMTB-C With ADHD Alone   [ Time Frame: Baseline, 32 Weeks ]

35.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Participants With Dyslexia Alone   [ Time Frame: Baseline, 32 Weeks ]

36.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia   [ Time Frame: Baseline, 32 Weeks ]

37.  Secondary:   Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With Dyslexia Alone   [ Time Frame: Baseline, 32 Weeks ]

38.  Secondary:   Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With ADHD or ADHD +Dyslexia   [ Time Frame: Baseline, 32 Weeks ]

39.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Participants With Dyslexia Alone   [ Time Frame: From Week 16, Up to 32 Weeks ]

40.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD + Dyslexia   [ Time Frame: From Week 16, Up to Week 32 ]

41.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Participants With ADHD Alone   [ Time Frame: From Week 16, Up to Week 32 ]

42.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With Dyslexia Alone   [ Time Frame: From Week 16, Up to Week 32 ]

43.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD + Dyslexia   [ Time Frame: From Week 16, Up to Week 32 ]

44.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Participants With ADHD Alone   [ Time Frame: From Week 16, Up to Week 32 ]

45.  Secondary:   Change From Baseline to Endpoint TOWRE Total Score in Participants With Dyslexia Alone   [ Time Frame: From Week 16, Up to Week 32 ]

46.  Secondary:   Change From Baseline to Endpoint in TOWRE Total Score in Participants With ADHD or ADHD + Dyslexia   [ Time Frame: From Week 16, Up to Week 32 ]

47.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With Dyslexia Alone   [ Time Frame: From Week 16, Up to Week 32 ]

48.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With ADHD+ Dyslexia   [ Time Frame: From Week 16, Up to Week 32 ]

49.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Participants With ADHD Alone   [ Time Frame: From Week 16, Up to Week 32 ]

50.  Secondary:   Change From Baseline to Endpoint in WMTB-C in Participants With Dyslexia Alone   [ Time Frame: From Week 16, Up to Week 32 ]

51.  Secondary:   Change From Baseline to Endpoint WMTB-C in Participants With ADHD + Dyslexia   [ Time Frame: From Week 16, Up to Week 32 ]

52.  Secondary:   Change From Baseline to Endpoint WMTB-C in Participants With ADHD Alone   [ Time Frame: From Week 16, Up to Week 32 ]

53.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Participants With Dyslexia Alone   [ Time Frame: From Week 16, Up to Week 32 ]

54.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Participants With ADHD or ADHD + Dyslexia   [ Time Frame: From Week 16, Up to Week 32 ]

55.  Secondary:   Change From Baseline to Endpoint in ADHDRS-IV Total Score in Participants With Dyslexia Alone   [ Time Frame: From Week 16, Up to Week 32 ]

56.  Secondary:   Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Participants With ADHD or ADHD + Dyslexia   [ Time Frame: From Week 16, Up to Week 32 ]

57.  Secondary:   The Number of Participants With Treatment Emergent Adverse Events (TEAE) in Participants With Dyslexia   [ Time Frame: 16 Weeks ]

58.  Secondary:   The Number of Participants With TEAE in Participants With ADHD or ADHD+Dyslexia.   [ Time Frame: 16 Weeks ]

59.  Secondary:   The Number of Participants With TEAE in Participants With Dyslexia   [ Time Frame: From 16 Weeks Up to Week 32 ]

60.  Secondary:   The Number of Participants With TEAE in Participants With ADHD or ADHD+Dyslexia.   [ Time Frame: From Week 16 Up to Week 32 ]

61.  Secondary:   Number of Participants With Adverse Events   [ Time Frame: 32 Weeks ]

62.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Healthy Participants   [ Time Frame: Baseline, 16 Weeks ]

63.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Healthy Participants   [ Time Frame: Baseline, 16 Weeks ]

64.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Healthy Participants   [ Time Frame: Baseline, 16 weeks ]

65.  Secondary:   Change From Baseline to Endpoint TOWRE Total Score in Healthy Participants   [ Time Frame: Baseline, 16 Weeks ]

66.  Secondary:   Change From Baseline to Endpoint in WMTB-C in Healthy Participants   [ Time Frame: Baseline, 16 Weeks ]

67.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Healthy Participants   [ Time Frame: Baseline, 16 Weeks ]

68.  Secondary:   Change From Baseline to Endpoint in ADHDRS-IV Total Score in Healthy Participants   [ Time Frame: Baseline, 16 Weeks ]

69.  Secondary:   Change From Baseline to Endpoint in WJ III Individual Scores in Healthy Participants   [ Time Frame: Baseline, 32 Weeks ]

70.  Secondary:   Change From Baseline to Endpoint in CTOPP Composite Scores in Healthy Participants   [ Time Frame: Baseline, 32 weeks ]

71.  Secondary:   Change From Baseline to Endpoint in GORT-4 in Healthy Participants   [ Time Frame: Baseline, 32 Weeks ]

72.  Secondary:   Change From Baseline to Endpoint in TOWRE Total Score in Healthy Participants   [ Time Frame: Baseline, 32 Weeks ]

73.  Secondary:   Change From Baseline to Endpoint in WMTB-C in Healthy Participants   [ Time Frame: Baseline, 32 Weeks ]

74.  Secondary:   Change From Baseline to Endpoint in BADD-A Total Score in Healthy Participants   [ Time Frame: Baseline, 32 Weeks ]

75.  Secondary:   Change From Baseline to Endpoint in ADHDRS-IV-Parent: Inv Total Score in Healthy Participants   [ Time Frame: Baseline, 32 Weeks ]

76.  Primary:   Change From Baseline to Endpoint in Functional Magnetic Resonance Imaging (fMRI) Activation in Participants With Dyslexia Alone (Pseudoword Rhyming and Semantic-category Tasks)   [ Time Frame: Baseline, 16 Weeks ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  

77.  Primary:   Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)   [ Time Frame: Baseline, 16 Weeks ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  

78.  Primary:   Change From Baseline to Endpoint in fMRI Activation in Participants With Attention Deficit Hyperactivity Disorder (ADHD) or ADHD + Dyslexia (Stroop Attention Tasks)   [ Time Frame: Baseline, 16 Weeks ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  

79.  Primary:   Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic-category Tasks)   [ Time Frame: Baseline, 16 Weeks ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  

80.  Secondary:   Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Pseudoword Rhyming and Semantic-category Tasks)   [ Time Frame: From Week 16, Up to Week 32 ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  

81.  Secondary:   Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Stroop Attention Tasks)   [ Time Frame: From Week 16, Up to 32 Weeks ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  

82.  Secondary:   Change From Baseline to Endpoint in fMRI Activation in Participants With Dyslexia Alone (Stroop Attention Tasks)   [ Time Frame: From Week 16, Up to Week 32 ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  

83.  Secondary:   Change From Baseline to Endpoint in fMRI Activation in Participants With ADHD or ADHD + Dyslexia (Pseudoword Rhyming and Semantic Tasks)   [ Time Frame: From Week 16, Up to Week 32 ]
Results not yet reported.   Anticipated Reporting Date:   08/2018  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979



Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00716274     History of Changes
Other Study ID Numbers: 12212
B4Z-US-LYEI ( Other Identifier: Eli Lilly and Company )
First Submitted: July 14, 2008
First Posted: July 16, 2008
Results First Submitted: June 26, 2017
Results First Posted: February 7, 2018
Last Update Posted: May 7, 2018