Trial Outcomes & Findings for Atomoxetine and Huntington's Disease (NCT NCT00368849)

NCT ID: NCT00368849

Last Updated: 2012-12-20

Results Overview

The Conners' Adult Attention Rating Scale (CAARS) is one of the most frequently used self-rating measures for adult Attention Deficit Hyperactivity Disorder (ADHD) and was given as a self-report measure of attention. It has 66 items with each item ranging from 0 to 3 points. Higher total scores represent greater impairment. The outcome reported was change in score from baseline for each treatment arm.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: There are two time points for this measure: baseline and after 4 weeks of treatment
• Results posted on: 2012-12-20

Participant Flow

Participants (number = 20) were recruited using advertisements and through the University of Iowa Huntington Disease (HD) Registry at a rate of 1.40 individuals per month from September 2006 through November 2007 (i.e., 14.3 months).

Participants were screened before baseline for the presence of attentional problems through interview, medical status (including safety laboratories and electrocardiogram), and history for inclusion/exclusion criteria.

Participant milestones

Measure	Atomoxetine (4 Weeks) Then Placebo (4 Weeks) Participants received 40 milligram twice a day atomoxetine for four weeks. After a two week wash out, they then received twice a day matching placebo for four weeks.	Placebo (4 Weeks) Then Atomoxetine (4 Weeks) Participants received twice a day matching placebo for four weeks. After a two week washout, they then received 40 milligram twice a day atomoxetine for four weeks.
Overall Study STARTED	10	10
Overall Study COMPLETED	10	8
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Atomoxetine (4 Weeks) Then Placebo (4 Weeks) Participants received 40 milligram twice a day atomoxetine for four weeks. After a two week wash out, they then received twice a day matching placebo for four weeks.	Placebo (4 Weeks) Then Atomoxetine (4 Weeks) Participants received twice a day matching placebo for four weeks. After a two week washout, they then received 40 milligram twice a day atomoxetine for four weeks.
Overall Study Withdrawal by Subject	0	1
Overall Study Physician Decision	0	1

Baseline Characteristics

Atomoxetine and Huntington's Disease

Baseline characteristics by cohort

Measure	All Participants n=20 Participants Age, sex, and region of enrollment were available for all 20 participants.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	46.20 years STANDARD_DEVIATION 10.288 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants

PRIMARY outcome

Timeframe: There are two time points for this measure: baseline and after 4 weeks of treatment

Population: Analysis was based on number of completers

The Conners' Adult Attention Rating Scale (CAARS) is one of the most frequently used self-rating measures for adult Attention Deficit Hyperactivity Disorder (ADHD) and was given as a self-report measure of attention. It has 66 items with each item ranging from 0 to 3 points. Higher total scores represent greater impairment. The outcome reported was change in score from baseline for each treatment arm.

Outcome measures

Measure	Atomoxetine n=18 Participants Individuals in this arm received 40 milligram twice a day atomoxetine	Placebo n=20 Participants Individuals in this arm received twice a day matching placebo.
Conners' Adult Attention Rating Scale (CAARS)	-2.88 units on a scale Standard Error 1.1	-2.24 units on a scale Standard Error 1.1

PRIMARY outcome

Timeframe: There are two time points for this measure: baseline and after 4 weeks of treatment

Population: Analysis was based on number of completers.

The attention composite comprises performance on Wechsler Adult Intelligence Scale III Symbol-Digit and Letter Number Sequencing Subtests, Trail Making Test Part A, computerized simple-choice reaction time, and computerized working memory (i.e., 2-Back). The composite score is the average combined z score for each test. Higher, positive values indicate better than average performance and negative and lower values indicate worse than average. The outcome reported was change in score from baseline for each treatment arm.

Outcome measures

Measure	Atomoxetine n=18 Participants Individuals in this arm received 40 milligram twice a day atomoxetine	Placebo n=20 Participants Individuals in this arm received twice a day matching placebo.
Attention Composite Score	-0.13 Units on a scale Standard Error 0.07	0.02 Units on a scale Standard Error 0.06

PRIMARY outcome

Timeframe: There are two time points for this measure: baseline and after 4 weeks of treatment

Population: Analysis was based on number of completers.

The executive composite comprises performance on Trail Making Test Part B, Stroop Color and Word Test, and the Controlled Oral Word Association Test (i.e., Verbal Fluency). The composite score is the average combined z score for each test. Positive values indicate better than average performance and negative values worse than average. The outcome reported was change in score from baseline for each treatment arm.

Outcome measures

Measure	Atomoxetine n=18 Participants Individuals in this arm received 40 milligram twice a day atomoxetine	Placebo n=20 Participants Individuals in this arm received twice a day matching placebo.
Executive Composite Score	-1.68 units on a scale Standard Error 1.4	-2.94 units on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: There are two time points for this measure: baseline and after 4 weeks of treatment

Population: Analysis was based on number of completers.

Psychiatric symptoms were evaluated with the Symptom Checklist-90-Revised, a self report measure of psychiatric symptoms. The measure produces raw scores and normed scores (T scores Mean = 50), with higher values representing greater impairment. The outcome reported was change in score from baseline for each treatment arm.

Outcome measures

Measure	Atomoxetine n=18 Participants Individuals in this arm received 40 milligram twice a day atomoxetine	Placebo n=20 Participants Individuals in this arm received twice a day matching placebo.
Symptom Checklist-90-Revised (SCL-90-R)	-4.20 units on a scale Standard Error 1.9	-4.64 units on a scale Standard Error 1.8

SECONDARY outcome

Timeframe: There are two time points for this measure: baseline and after 4 weeks of treatment

Population: Analysis was based on number of completers.

Although changes in motor symptoms were not hypothesized, the Unified Huntington Disease Rating Scale motor examination was administered at every visit. An experienced motor rater completes a motor examination and rates the participant on several motor tasks. Total score ranges from 0 - 124, with higher scores indicating a worse outcome. The outcome reported was change in score from baseline for each treatment arm.

Outcome measures

Measure	Atomoxetine n=18 Participants Individuals in this arm received 40 milligram twice a day atomoxetine	Placebo n=20 Participants Individuals in this arm received twice a day matching placebo.
Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score	0.42 units on a scale Standard Error 1.8	-0.35 units on a scale Standard Error 1.7

Adverse Events

Atomoxetine

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Matching Placebo

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Atomoxetine n=18 participants at risk；n=20 participants at risk Individuals in this arm received 40 milligram twice a day atomoxetine.	Matching Placebo n=20 participants at risk Individuals in this arm received twice a day matching placebo.
Psychiatric disorders Inpatient Hospitalization	0.00% 0/20 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	5.0% 1/20 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Renal and urinary disorders An Important Medical Event	0.00% 0/20 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	5.0% 1/20 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Psychiatric disorders An Important Medical Event	0.00% 0/20 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	5.0% 1/20 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)

Other adverse events

Measure	Atomoxetine n=18 participants at risk；n=20 participants at risk Individuals in this arm received 40 milligram twice a day atomoxetine.	Matching Placebo n=20 participants at risk Individuals in this arm received twice a day matching placebo.
Metabolism and nutrition disorders Weight Loss	11.1% 2/18 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	10.0% 2/20 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Gastrointestinal disorders Constipation	11.1% 2/18 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	0.00% 0/20 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Metabolism and nutrition disorders Appetite Loss	22.2% 4/18 • Number of events 4 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	0.00% 0/20 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Gastrointestinal disorders Nausea	11.1% 2/18 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	0.00% 0/20 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Gastrointestinal disorders Xerostomia	38.9% 7/18 • Number of events 7 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	10.0% 2/20 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Nervous system disorders Dizziness	16.7% 3/18 • Number of events 3 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	10.0% 2/20 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Nervous system disorders Insomnia	22.2% 4/18 • Number of events 4 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	5.0% 1/20 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Nervous system disorders Headache	11.1% 2/18 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	5.0% 1/20 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Renal and urinary disorders Difficulty Urinating	11.1% 2/18 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	— 0/0 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Renal and urinary disorders Urine Retention	11.1% 2/18 • Number of events 2 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	0.00% 0/20 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/18 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	5.0% 1/20 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)
Nervous system disorders Somnolence	5.6% 1/18 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)	5.0% 1/20 • Number of events 1 • Adverse events were reported from September 2006 through November 2007 (14.3 months)

Additional Information

Leigh J. Beglinger, Ph.D.

The University of Iowa

Phone: 319-335-8765

Email: leigh-beglinger@uiowa.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place