Comparison of Continuous and Pulsatile Apomorphine in Parkinson's Disease
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the effects of apomorphine, given by two different methods, to determine how best to manage dyskinesias.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Levodopa is a drug that can be taken by mouth, and improves the symptoms of Parkinson's disease (PD). However it can eventually cause involuntary movements called dyskinesia and motor fluctuations-fluctuations in the control of symptoms, often referred to as "off" and "on." Apomorphine is a drug that works as well as levodopa, but does not work if taken by mouth.
The purpose of this study is to compare the effects of apomorphine in people with PD who have levodopa-induced motor fluctuations and dyskinesias. In the trial, researchers will compare the effects of apomorphine administered by subcutaneous bolus injections (pulsatile) and by ambulatory infusion pumps (continuous) in 24 people with PD, for 6 months.
After an initial screening, potential participants will undergo a test to verify that they can tolerate and respond to apomorphine. Those who meet all of the requirements will be randomized to receive the study drug via injections (shots) using an injector pen or a portable infusion pump. Apomorphine will be given either continuously using the portable pump during the waking day or intermittently by injection, for 6 months. The pump will be carried on a belt and connected by a tube to a small needle under the skin. Injections of apomorphine under the skin will be self-administered by the participants or administered by friends or family members using injector pens.
After 6 months, the effects of apomorphine use will be assessed by measuring how the participants respond to levodopa and by measuring their symptoms during the course of the study. Participants will be followed initially every week, then biweekly, and then monthly in an outpatient clinic for 6 months. During this time, they may receive adjustments of apomorphine doses as well as doses of other antiparkinson medications.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ambulatory Pump Participants will receive apomorphine via a pump. Participants in the Continuous Delivery Arm will self-administer apomorphine continuously (12-14 hours a day) using a portable pump. |
Drug: Apomorphine
Participants in both arms will receive the study drug apomorphine for 6 months. One group will receive it continuously using a portable pump during waking hours, and the other group will receive it intermittently by bolus injections. The continuous delivery group will receive up to 100 mg apomorphine per 24 hours, delivered subcutaneously by ambulatory pump. The intermittent delivery group will receive up to 5 subcutaneous injections totaling up to 20 mg daily.
Other Names:
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| Active Comparator: Subcutaneous Injections Participants will receive apomorphine via an injection pen. Participants in the Intermittent Delivery Arm will self-administer apomorphine at intervals, via a injection, using pen injector. |
Drug: Apomorphine
Participants in both arms will receive the study drug apomorphine for 6 months. One group will receive it continuously using a portable pump during waking hours, and the other group will receive it intermittently by bolus injections. The continuous delivery group will receive up to 100 mg apomorphine per 24 hours, delivered subcutaneously by ambulatory pump. The intermittent delivery group will receive up to 5 subcutaneous injections totaling up to 20 mg daily.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change in dyskinesia severity and duration during the levodopa infusion, measured with a clinical rating scale during two-hour levodopa infusion [at baseline and after 6 months]
Secondary Outcome Measures
- Improvement in motor performance, measured as change in tapping speed during levodopa infusion [at baseline and after 6 months]
- Improvement in "on" time, as measured by subject diaries [at baseline and after 6 months]
- Reduction in levodopa and adjunct drug use [at baseline and after 6 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
idiopathic Parkinson's Disease
-
clear response to levodopa (sinemet)
-
"off" at least 20% of waking day
-
dyskinesias present for at least two hours of waking day
-
subject or caregiver able to master use of drug delivery system (injector pen or pump)
Exclusion Criteria:
-
physical complications that would preclude safe participation
-
standing systolic BP of <80
-
lack of tolerance or response to apomorphine
-
drug/alcohol abuse
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
Sponsors and Collaborators
- Oregon Health and Science University
- National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
- Principal Investigator: John G. Nutt, MD, Oregon Health and Science University
Study Documents (Full-Text)
None provided.More Information
Publications
- Manson AJ, Turner K, Lees AJ. Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson's disease: long-term follow-up study of 64 patients. Mov Disord. 2002 Nov;17(6):1235-41.
- Stocchi F, Ruggieri S, Vacca L, Olanow CW. Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease. Brain. 2002 Sep;125(Pt 9):2058-66.
- Stocchi F, Vacca L, Ruggieri S, Olanow CW. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005 Jun;62(6):905-10.
- R01NS021062-21
- R01NS021062-21
- eIRB 2167