Trial Outcomes & Findings for Treatment of Executive Dysfunction in Parkinson's Disease (NCT NCT00286949)
NCT ID: NCT00286949
Last Updated: 2017-11-06
Results Overview
CGIC-C score is a clinician's rating of change (improvement or worsening) over the course of the trial in an individual's symptoms and their global impact on function and clinical status, i.e., the global impact of the intervention that the patient is better, unchanged, or worse). Scale ranges1 to 7 which equates to from very much worse to very much improved. The CGIC-C score is not an appropriate baseline measure since it represents change after initiating an intervention. In addition, a baseline Clinical Global Impression of Severity-Clinician Rated Score (CGIS-C) is not appropriate to compare to CGIC-C, as a patient with severe disease might show clinically meaningful improvement (i.e., very much improved) from an intervention while still being severely affected on the CGIS-C score; by contrast, a patient with mild CGIS-C could have minimal or no change on the CGIC-C score. This study was not designed to assess the influence of disease severity on the primary outcome (CGIC-C).
COMPLETED
NA
12 participants
8 weeks
2017-11-06
Participant Flow
Parkinson's disease (PD) outpatients (recruited 2005-2008 via Johns Hopkins clinics and community) had clinically significant Executive Dysfunction, defined as moderately severe problems with disorganization, distractibility, task completion, planning or problem solving that impaired function, were a decline from pre-PD, and verified by informant.
All enrolled subjects were assigned to and received open label atomoxetine.
Participant milestones
| Measure |
Atomoxetine Open Label
This open-label, uncontrolled, single arm, flexible dose trial consisted of atomoxetine (Strattera) in 25 mg capsules initiated at 25 mg/day in the morning (Week 1) and advancing to 50mg/at (weeks 2-4), 75 mg/day (Week 5), and 100 mg/day (Weeks 6-8). Dose reductions were allowed to a minimum of 2.5 mg/day for intolerance.
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|---|---|
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Overall Study
STARTED
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12
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Overall Study
COMPLETED
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12
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treatment of Executive Dysfunction in Parkinson's Disease
Baseline characteristics by cohort
| Measure |
Atomoxetine
n=12 Participants
Atomoxetine (Strattera): Open label, no comparator
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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12 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Age, Continuous
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57.3 years
STANDARD_DEVIATION 7.2 • n=5 Participants
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Sex: Female, Male
Female
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7 Participants
n=5 Participants
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Sex: Female, Male
Male
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5 Participants
n=5 Participants
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Region of Enrollment
United States
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12 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: 8 weeksCGIC-C score is a clinician's rating of change (improvement or worsening) over the course of the trial in an individual's symptoms and their global impact on function and clinical status, i.e., the global impact of the intervention that the patient is better, unchanged, or worse). Scale ranges1 to 7 which equates to from very much worse to very much improved. The CGIC-C score is not an appropriate baseline measure since it represents change after initiating an intervention. In addition, a baseline Clinical Global Impression of Severity-Clinician Rated Score (CGIS-C) is not appropriate to compare to CGIC-C, as a patient with severe disease might show clinically meaningful improvement (i.e., very much improved) from an intervention while still being severely affected on the CGIS-C score; by contrast, a patient with mild CGIS-C could have minimal or no change on the CGIC-C score. This study was not designed to assess the influence of disease severity on the primary outcome (CGIC-C).
Outcome measures
| Measure |
Atomoxetine Open Label
n=12 Participants
Active open label drug, no comparator; Atomoxetine (Strattera)
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|---|---|
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Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
Very Much Improved
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3 Participants
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Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
Much Improved
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6 Participants
|
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Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
Minimally Improved
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1 Participants
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Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
No Change
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2 Participants
|
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Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
Minimally Worse
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0 Participants
|
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Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
Much Worse
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0 Participants
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Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
Very Much Worse
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0 Participants
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PRIMARY outcome
Timeframe: baseline and 8 weeksThe CAARS-L Inattention/Memory subscale, a primary self-rated outcome measure in this study, measures the frequency of behaviors associated with executive dysfunction, such as task incompletion, disorganization, distractibility, and difficulty planning, multi-tasking, and initiating tasks. CAARS-L scores are depicted as group Mean (SD) T scores, derived from comparison to CAARS norms based on gender and age in a normative sample. Similar to the FrSBE, higher T-scores are associated with greater symptom severity and T-scores above 65 represent symptoms of clinical significance.
Outcome measures
| Measure |
Atomoxetine Open Label
n=12 Participants
Active open label drug, no comparator; Atomoxetine (Strattera)
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|---|---|
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Connors Adult Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale-Long Form (CAARS-L) Inattention/Memory Subscale
Baseline Visit
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60 units on a scale
Standard Deviation 10
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Connors Adult Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale-Long Form (CAARS-L) Inattention/Memory Subscale
Final Visit (8 weeks)
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52 units on a scale
Standard Deviation 10
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PRIMARY outcome
Timeframe: 8 weeksFrontal Systems Behavioral Scale (FrSBe) Executive Function subscore is on of the 3 subscales of the FrSBE, a scale designed to identify and quantify behavioral problems associated with frontal lobe dysfunction. The other subscales are Apathy and Disinhibition. Each item is rated on a 5-point Likert scale. Totals are generated for each subscale and normative data is referenced (based on patient gender, age and education) and standardized T-scores are determined). For all FrSBe scales, T scores ≥ 65 are considered clinically significant and scores of 60 to 64 represent likely borderline impairment.
Outcome measures
| Measure |
Atomoxetine Open Label
n=12 Participants
Active open label drug, no comparator; Atomoxetine (Strattera)
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|---|---|
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Frontal Systems Behavioral Scale (FrSBe) Executive Function Subscore
Baseline Visit
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67 T-score
Standard Deviation 11
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Frontal Systems Behavioral Scale (FrSBe) Executive Function Subscore
Final Visit
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58 T-score
Standard Deviation 15
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Adverse Events
Atomoxetine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Atomoxetine
n=12 participants at risk
Open label, no comparator
Atomoxetine (Strattera)
|
|---|---|
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Psychiatric disorders
Hypomania
|
8.3%
1/12 • Number of events 1 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
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|
Nervous system disorders
Reduced Sleep
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50.0%
6/12 • Number of events 6 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Gastrointestinal disorders
Constipation
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41.7%
5/12 • Number of events 5 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
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Gastrointestinal disorders
Nausea/vomiting
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25.0%
3/12 • Number of events 3 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
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Nervous system disorders
Confusion
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25.0%
3/12 • Number of events 3 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
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Nervous system disorders
Slowed movements
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25.0%
3/12 • Number of events 3 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Skin and subcutaneous tissue disorders
Diaphoresis
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25.0%
3/12 • Number of events 3 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
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General disorders
Fatigue
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16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
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Psychiatric disorders
Depression
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16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
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Psychiatric disorders
Agitation
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16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
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Nervous system disorders
increased dream activity
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Nervous system disorders
Rigidity
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
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Nervous system disorders
Hyperkinetic movements
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16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Nervous system disorders
paresthesias
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Nervous system disorders
Headaches
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
General disorders
Dry mouth
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Cardiac disorders
Tachycardia
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
General disorders
Weight gain
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
16.7%
2/12 • Number of events 2 • 8 weeks
Vital signs, spontaneously reported adverse events (AEs), Udvalg for Kliniske Undersogelser (UKU) AE checklist,Unified Parkinson's Disease RatingScale (UPDRS)-Activities of Daily Living, Motor, and Complications of Therapy subscales,Hoehn and Yahr Stage,changes from baseline labor tests, and cardiovascular effects
|
Additional Information
Laura Marsh, M.D., Principal Investigator
Michael E. DeBakey VA Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place