Clinical trial NCT00477802: Botulinum Toxin Type A (Botox) in the Management of Levodopa-Induced Peak-Dose Dyskinesias in Parkinson's Disease
Official title: Botulinum Toxin Type A (Botox) in the Management of Levodopa-Induced Peak-Dose Dyskinesias in Parkinson's Disease: A Double-Blind, Randomized, Placebo Controlled, Cross-Over Design Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Parkinson Disease
Keywords: Parkinson's disease
levodopa-induced cervical dyskinesias
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2007-05-24
Enrollment: 8
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine whether intramuscular injections of botulinum toxin type A (Botox®) in selected cervical muscles at antidystonic dosages can reduce levodopa-induced peak-dose dyskinesias (LID) in the cervical region in adult patients with idiopathic Parkinson's disease. It is hypothesized that the intramuscular injection of antidystonic doses of botulinum toxin into cervical muscles will decrease the duration and severity of LID in the cervical region in patients with Parkinson's disease (PD).

Detailed description: The study will follow a cross-over design to maximize statistical power and decrease biases inherent to small samples as patients will become their own controls. After a baseline assessment, patients will be randomized to receive either botulinum toxin or an equal amount and distribution of normal saline (placebo). Patients will undergo reassessment of function at one and four weeks after the initial and second session of injections. The second procedure will occur, using the opposite treatment arm (Botox® or saline placebo), three months after the first injection session. Doses of levodopa, dopaminergic agonists, and antidyskinetic drugs if applicable, will be kept constant throughout the study. All study assessments will be carried out at the time treatment is expected to cause the greatest severity of LID.

Eligibility criteria: Inclusion Criteria:

1. Patients must have idiopathic PD (by standard clinical criteria).
2. Patients must have persistence of LID despite optimization of anti-Parkinsonian medication (duration of LID \> 1 \[duration of at least 1-25% of the waking time\] on item 32 of the United Parkinson's Disease Rating Scale \[UPDRS\]).
3. Patients must have severity of LID \> 1 \[mildly disabling\] on item 33 of the UPDRS.
4. Patients must have a Mini-Mental State score of \> 24.
5. Patients must be willing and able to give consent.

Exclusion Criteria:

1. Patients who are older than 75 years of age.
2. Patients who have a Parkinsonian syndrome that is unresponsive or weakly responsive to levodopa (improvement \< 30%).
3. Patients who require concurrent use of warfarin or other anticoagulating agents.
4. Uncontrolled clinically significant medical condition other than the condition under evaluation
5. Known allergy or sensitivity to any of the components in the study medication.
6. Concurrent participation in another investigational drug or device study or participation in the 30 days immediately prior to study enrollment.
7. Any medical condition that may put the subject at an increased risk with exposure to Botox including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disorder that might interfere with neuromuscular function.
8. Evidence of recent alcohol or drug abuse.
9. Infection or skin disorder at an anticipated injection site (if applicable).
10. Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.

Primary outcomes:
measure: the change in the "on" time with LID 1 month and 3 months after injected compared to baseline scores. A reduction of 40% in the mean "on" time with LID in the Botox® group compared to the placebo group will be considered significant.
timeFrame: 1 and 3 months after injection
Secondary outcomes:
measure: changes in: the duration, severity, and pain of LID using the UPDRS Part IV, physician and patient Clinical Global Impression [CGI] of change, Schwab & England score, Abnormal Involuntary Movement Scale, 4-point modified dyskinesia rating scale (Goetz)
timeFrame: 1 and 3 months after injection
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University Neurology - Movement Disorders Clinic
state: Ohio
Study officials:
affiliation: University of Cincinnati- Neurology
name: Alberto Espay, MD
role: PRINCIPAL_INVESTIGATOR
References: