Atomoxetine and Huntington's Disease

Study Overview
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Brief Summary
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The purpose of this research study is to evaluate the effect of atomoxetine (also known as Strattera) compared to placebo (inactive substance) on daily activities such as attention and focus, thinking ability and muscle movements in subjects with early Huntington Disease (HD) and attention deficit disorder (ADD).

Detailed Description
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No medications have been investigated to improve attention and executive functions in patients with Huntington's disease, despite the evidence that these cognitive domains can be abnormal even before motor symptom onset. Because cognitive symptoms are highly associated with functional disability, treatments aimed at improving cognitive functions would be of significant benefit to patients in the early stages of the disease. Atomoxetine is the ideal choice for such a trial. It has proven efficacy in adults with attention deficit hyperactivity disorder (ADHD) and it selectively targets norepinephrine and dopamine in the prefrontal cortex rather than in subcortical areas. This selectivity is an advantage for patients with HD, because motor side effects are less likely to be facilitated than with a psychostimulant. The present study is a feasibility study in which we propose to administer either 80 milligram (mg) atomoxetine for 4 weeks or placebo to 20 patients with early HD who also complain of mild cognitive symptoms. The groups will then crossover to the other condition (atomoxetine or placebo). Participants will be assessed on measures of ADHD symptoms and a sensitive battery of neuropsychological tests. Based on the shared neural circuitry in ADHD and HD, and the demonstrated effectiveness of atomoxetine on attention in adults with ADHD, improved performance on cognitive tests of attention and executive functions and on subjects' report of ADHD symptoms are expected in the atomoxetine treatment phase. No changes in motor status are predicted during the study.

Official Title
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Atomoxetine for Attention Deficits in Adults With Mild HD: A Randomized, Placebo-Controlled Crossover Study

Conditions
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Huntington Disease, Chorea

Intervention / Treatment
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* Drug: atomoxetine
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed Huntington's disease (HD) diagnosis Age 18 to 65 Must have mild HD Must have complaints of poor attention Exclusion Criteria: Childhood history of attention deficit hyperactivity disorder (ADHD) symptoms Diagnosis of schizophrenia, bipolar affective disorder, dementia, delirium or severe anxiety Current use of a monoamine oxidase inhibitor (MAOI) medication Pregnancy Uncontrolled hypertension Tachycardia Cardiovascular or cerebrovascular disease History of a loss of consciousness for greater than (or equal to) 5 minutes Having any neurological disorder or insult other than Huntington disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40 milligram twice a day atomoxetine<br>Participants received 40 milligram twice a day atomoxetine for 4 weeks. | Drug: atomoxetine<br>* This study utilizes a crossover design. Accordingly, half of the participants receive 40 milligram twice a day atomoxetine at arm one while the remaining half receive this intervention at arm two.<br>* Other names: Strattera;|
| Placebo Comparator: Twice a day matching placebo<br>Participants received twice a day matching placebo for 4 weeks. | Drug: Matching Placebo<br>* This study utilizes a crossover design. Accordingly, half of the participants receive twice a day matching placebo at arm one while the remaining half receive this intervention at arm two.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conners' Adult Attention Rating Scale (CAARS) | 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. | There are two time points for this measure: baseline and after 4 weeks of treatment | 
| Attention Composite Score | 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. | There are two time points for this measure: baseline and after 4 weeks of treatment | 
| Executive Composite Score | 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. | There are two time points for this measure: baseline and after 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom Checklist-90-Revised (SCL-90-R) | 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. | There are two time points for this measure: baseline and after 4 weeks of treatment | 
| Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score | 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. | There are two time points for this measure: baseline and after 4 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington Disease, Chorea, Attention, ADHD, ADD, Strattera, Atomoxetine