Clinical trial NCT00758368: Comparison of Continuous and Pulsatile Apomorphine in Parkinson's Disease
Official title: Comparison of Continuous and Pulsatile Apomorphine Administration in Parkinson's Disease Complicated by Levodopa-induced Dyskinesia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
PD
pulsatile apomorphine
dyskinesia
apomorphine
continuous dopaminergic stimulation
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2008-09-25
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in dyskinesia severity and duration during the levodopa infusion, measured with a clinical rating scale during two-hour levodopa infusion
timeFrame: at baseline and after 6 months
Secondary outcomes:
measure: Improvement in motor performance, measured as change in tapping speed during levodopa infusion
timeFrame: at baseline and after 6 months
measure: Improvement in "on" time, as measured by subject diaries
timeFrame: at baseline and after 6 months
measure: Reduction in levodopa and adjunct drug use
timeFrame: at baseline and after 6 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: John G. Nutt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1002/mds.10281.
citation: 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. doi: 10.1093/brain/awf214.
citation: 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. doi: 10.1001/archneur.62.6.905.