Parkinson's DiseaseNCT00286949

Treatment of Executive Dysfunction in Parkinson's Disease

A study testing Atomoxetine in people with Parkinson's Disease, run by Johns Hopkins University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Atomoxetine (Strattera) is a drug that is currently approved for treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. Atomoxetine works to enhance levels of brain chemicals that may be affected in people with executive dysfunction, (difficulties with organization, task completion, and… Read more about this study

Who is it for?: Ages 21 to 65 years
Conditions the study is for: Parkinson's Disease
What is being tested?: Atomoxetine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 6 Jan 2005to 30 Jun 2008
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Men and women with idiopathic Parkinson's Disease, as defined by United Kingdom (UK) Brain Bank Criteria.
Adults, ages 21 to 65 years old.
Clinically significant executive dysfunction, as defined by the reported presence of problems with disorganization, distractibility, task completion, planning or problem solving that represents a decline from premorbid (pre-PD) status and is confirmed by the patient's informant.
Mini-Mental State Exam (MMSE) score > 26.
Absence of Dementia due to Parkinson's Disease, as defined by Diagnostic and Statistical Manual-IVth edition-Text revision (DSM-IV-TR).
Clinical Dementia Rating (CDR) Scale score < 1.

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Functional Assessment Staging (FAST) score < 4.
Hamilton Depression Rating Scale (HDRS) Score < 11.
Able to provide informed consent and participate in follow-up visits during the 8-week study duration.
Availability of informant who knows the patient well and is willing to provide collateral information on the patient's clinical status and response to treatment.
On stable antiparkinsonian therapy for 3 months.
Any stage of PD severity, e.g., Hoehn and Yahr stage I-V, but must be able to participate in testing battery and be capable of independent function so as to manifest executive dysfunction.
Stable medical health with stable medication regimen for 3 months.
If history of major depression or anxiety disorder, must have stable symptoms and be on stable therapy for 3 months.
For women of childbearing potential, negative pregnancy test and reliable use of contraception.

Who cannot join

Prior exposure to atomoxetine within the last 6 months.
Current problems with urinary hesitancy or urinary retention.
Uncontrolled hypertension or tachycardia.
Narrow angle glaucoma.
Current presence of hallucinations without insight or uncontrolled delusions (patients with benign visual hallucinations of any sensory modality with insight, e.g., passage or presence hallucinations, or controlled stable delusions will be enrolled).
Illicit substance use or alcohol abuse or dependence within the last 6 months.

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Current symptomatic Major Depressive Disorder or Anxiety Disorder that warrants additional treatment, as assessed on clinical interview, or 21-item Hamilton Depression Scale > 10.
For women, current pregnancy or nursing.
Current use of potent CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, quinidine.
Current use of stimulant or wakefulness therapy, e.g., methylphenidate or modafinil.
Current hepatic dysfunction, defined as values of two times or greater than the upper limit of normal on the aspartate aminotransferase (AST) or alanine aminotransferase (ALT) hepatic enzymes or any disorder affecting the liver that in the opinion of the enrolling investigator would interfere with hepatic metabolism of the medication or interfere with the participant's ability to complete the study.
Current use of monoamine oxidase inhibitors that are typically used for treatment of depression (isocarboxazid, phenelzine, and tranylcypromine).

Trial locations and contacts

1 site in 1 country.

United States1 site

Johns Hopkins Hospital
Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: Atomoxetine for the Treatment of Executive Dysfunction in Patients With Parkinson's Disease: A Pilot Open-label Study

The goal of this study is to provide preliminary data on the effectiveness and tolerability of atomoxetine for the treatment of executive dysfunction in patients with PD.

Read the detailed description

Parkinson's disease (PD), while defined by its motor abnormalities and associated dopaminergic loss, is invariably accompanied by cognitive impairment. Early in the disease course, the deficits are characterized by executive dysfunction with difficulties on tasks that involve information processing, attention, sorting, planning, set-shifting, and working memory and are subserved by neural connections with prefrontal brain regions. There has been little effort to identify treatments for these PD-related cognitive impairments, despite their disabling and distressing effects. Accordingly, the goal of this proposal is to conduct a small pilot study to determine the effectiveness and tolerability of atomoxetine, a selective norepinephrine reuptake inhibitor, for the treatment of executive dysfunction in patients with PD.

Atomoxetine (Strattera) is currently approved by the FDA for treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. Atomoxetine enhances dopaminergic and noradrenergic transmission in frontal regions that are also implicated in executive dysfunction and thus has the potential to improve executive dysfunction in PD as well as other neurological conditions. Results of the study will be used to develop a larger placebo-controlled trial of atomoxetine, if appropriate, as well as inform the design of other clinical trials on potential treatments for cognitive dysfunction in PD.

The overall hypothesis is that atomoxetine will be an effective and safe treatment for executive dysfunction in PD.

Conditions: Parkinson's Disease
Being tested: Atomoxetine
Keywords: Parkinson's disease, executive dysfunction, impairment, motor skills, cognitive
Medical subject headings: Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AtomoxetineDrug
Also called Strattera (Brand Name)
Open Label uncontrolled active Drug intervention

Study groups in NCT00286949
Study group	Role	What they receive
Atomoxetine (Strattera)	Other	Open-Label Uncontrolled Active Drug Intervention, No comparator Receives: Drug: Atomoxetine

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
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).
Measured: 8 weeks
Connors Adult Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale-Long Form (CAARS-L) Inattention/Memory Subscale
The 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.
Measured: baseline and 8 weeks
Frontal Systems Behavioral Scale (FrSBe) Executive Function Subscore
Frontal 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.
Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Jan 200530 Jun 2008

First posted6 Feb 2006 (estimated)
Study start6 Jan 2005
Primary completion30 Jun 2008
Study completion30 Jun 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00286949
Sponsor's protocol ID: WIRB#20040223
Other IDs: B4Z-US-X029
Status last verified: Oct 2017
First submitted: 3 Feb 2006
Last updated: 6 Nov 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Marsh L, Biglan K, Gerstenhaber M, Williams JR. Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: a pilot open-label study. Mov Disord. 2009 Jan 30;24(2):277-82. doi: 10.1002/mds.22307.
PubMed 19025777

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Atomoxetine for the Treatment of Executive Dysfunction in Patients With Parkinson's Disease: A Pilot Open-label Study
ClinicalTrials.gov ID: NCT00286949
Acronym / sponsor ID: WIRB#20040223
Conditions: Parkinson's Disease
Keywords: Parkinson's disease, executive dysfunction, impairment, motor skills, cognitive
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Johns Hopkins UniversityUniversity, hospital or other
Collaborators: Eli Lilly and Company
Study start: 6 Jan 2005 (actual)
Primary completion: 30 Jun 2008 (actual)
Study completion: 30 Jun 2008 (actual)
First posted: 6 Feb 2006 (estimated)
Results: Posted 18 Sep 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The goal of this study is to provide preliminary data on the effectiveness and tolerability of atomoxetine for the treatment of executive dysfunction in patients with PD.

Detailed description

The overall hypothesis is that atomoxetine will be an effective and safe treatment for executive dysfunction in PD.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Atomoxetine (Strattera)	Other	Drug: AtomoxetineOpen-Label Uncontrolled Active Drug Intervention, No comparator

Who may qualify

Ages: 21 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Men and women with idiopathic Parkinson's Disease, as defined by United Kingdom (UK) Brain Bank Criteria.
Adults, ages 21 to 65 years old.
Clinically significant executive dysfunction, as defined by the reported presence of problems with disorganization, distractibility, task completion, planning or problem solving that represents a decline from premorbid (pre-PD) status and is confirmed by the patient's informant.
Mini-Mental State Exam (MMSE) score > 26.
Absence of Dementia due to Parkinson's Disease, as defined by Diagnostic and Statistical Manual-IVth edition-Text revision (DSM-IV-TR).

Key exclusion criteria (12 listed)

Prior exposure to atomoxetine within the last 6 months.
Current problems with urinary hesitancy or urinary retention.
Uncontrolled hypertension or tachycardia.
Narrow angle glaucoma.
Current presence of hallucinations without insight or uncontrolled delusions (patients with benign visual hallucinations of any sensory modality with insight, e.g., passage or presence hallucinations, or controlled stable delusions will be enrolled).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AtomoxetineAlso: Strattera (Brand Name)Open Label uncontrolled active Drug intervention	Drug	Atomoxetine (Strattera)

Primary outcome

Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)
Time frame: 8 weeks
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).
Connors Adult Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale-Long Form (CAARS-L) Inattention/Memory Subscale
Time frame: baseline and 8 weeks
The 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.
Frontal Systems Behavioral Scale (FrSBe) Executive Function Subscore
Time frame: 8 weeks
Frontal 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.

Results and safety

Results posted to the registry on 18 Sep 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Atomoxetine Open Label	12	12

Primary outcome: Clinical Global Impression of Change-Clinician Rated Score (CGIC-C)

Time frame: 8 weeks. Count of participants. Unit: Participants

Measure	Atomoxetine Open Label n = 12
Very Much Improved	3
Much Improved	6
Minimally Improved	1
No Change	2
Minimally Worse	0
Much Worse	0
Very Much Worse	0

Primary outcome: Connors Adult Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale-Long Form (CAARS-L) Inattention/Memory Subscale

Time frame: baseline and 8 weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	Atomoxetine (Strattera) n = 12
Baseline Visit	60 (10)
Final Visit (8 weeks)	52 (10)

Primary outcome: Frontal Systems Behavioral Scale (FrSBe) Executive Function Subscore

Time frame: 8 weeks. Mean (Standard Deviation). Unit: T-score

Measure	Atomoxetine n = 12
Baseline Visit	67 (11)
Final Visit	58 (15)

Adverse events

Time frame: 8 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Atomoxetine	0 of 12 (0%)	12 of 12 (100%)	0 of 12

Limitations and caveats (from the sponsor): Data interpretation limited by open-label uncontrolled design, small sample size, subjects young (\< age 65 years); multiple comparisons, intersubject variability, possible inclusion bias, ceiling and practice effects for neuropsychological data.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19025777Marsh L, Biglan K, Gerstenhaber M, Williams JR. Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: a pilot open-label study. Mov Disord. 2009 Jan 30;24(2):277-82. doi: 10.1002/mds.22307.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Laura Marsh, MD principal investigator

Johns Hopkins University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Atomoxetine in people with Parkinson's Disease, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Global Impression of Change-Clinician Rated Score (CGIC-C) (time frame: 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00286949, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.