Treatment of Executive Dysfunction in Parkinson's Disease

NCT ID: NCT00286949

Last Updated: 2017-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-06
• Study Completion Date: 2008-06-30

Brief 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 priority setting). Thus, atomoxetine has the potential to improve executive dysfunction in people with Parkinson's disease (PD).

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

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

Keywords

Parkinson's disease; executive dysfunction; impairment; motor skills; cognitive

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atomoxetine (Strattera)

Open-Label Uncontrolled Active Drug Intervention, No comparator

Group Type: OTHER

Atomoxetine

Intervention Type: DRUG

Open Label uncontrolled active Drug intervention

Interventions

Atomoxetine

Open Label uncontrolled active Drug intervention

Intervention Type: DRUG

Other Intervention Names

Strattera (Brand Name)

Eligibility Criteria

Inclusion Criteria

1. Men and women with idiopathic Parkinson's Disease, as defined by United Kingdom (UK) Brain Bank Criteria.

2. Adults, ages 21 to 65 years old.

3. 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.

4. Mini-Mental State Exam (MMSE) score > 26.

5. Absence of Dementia due to Parkinson's Disease, as defined by Diagnostic and Statistical Manual-IVth edition-Text revision (DSM-IV-TR).

6. Clinical Dementia Rating (CDR) Scale score < 1.

7. Functional Assessment Staging (FAST) score < 4.

8. Hamilton Depression Rating Scale (HDRS) Score < 11.

9. Able to provide informed consent and participate in follow-up visits during the 8-week study duration.

10. 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.

11. On stable antiparkinsonian therapy for 3 months.

12. 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.

13. Stable medical health with stable medication regimen for 3 months.

14. If history of major depression or anxiety disorder, must have stable symptoms and be on stable therapy for 3 months.

15. For women of childbearing potential, negative pregnancy test and reliable use of contraception.

Exclusion Criteria

1. Prior exposure to atomoxetine within the last 6 months.

2. Current problems with urinary hesitancy or urinary retention.

3. Uncontrolled hypertension or tachycardia.

4. Narrow angle glaucoma.

5. 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).

6. Illicit substance use or alcohol abuse or dependence within the last 6 months.

7. Current symptomatic Major Depressive Disorder or Anxiety Disorder that warrants additional treatment, as assessed on clinical interview, or 21-item Hamilton Depression Scale > 10.

8. For women, current pregnancy or nursing.

9. Current use of potent CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, quinidine.

10. Current use of stimulant or wakefulness therapy, e.g., methylphenidate or modafinil.

11. 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.

12. Current use of monoamine oxidase inhibitors that are typically used for treatment of depression (isocarboxazid, phenelzine, and tranylcypromine).

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laura Marsh, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 19025777 (View on PubMed)

Other Identifiers

B4Z-US-X029

Identifier Type: OTHER

Identifier Source: secondary_id

WIRB#20040223

Identifier Type: -

Identifier Source: org_study_id