Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00076674
Status:
COMPLETED
Last Update Posted:
2016-09-22
First Post:
2004-01-28
Brief Title:
Levetiracetam Treatment of L-dopa Induced Dyskinesias
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Levetiracetam Treatment of L-dopa Induced Dyskinesias
Status:
COMPLETED
Status Verified Date:
2005-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the effects of levetiracetam Keppra Trademark on Parkinsons disease symptoms and on dyskinesias involuntary movements that develop as a result of long-term treatment with levodopa Levetiracetam blocks certain protein receptors on brain cells and thus can change the spread of brain signals believed to be affected in patients with Parkinsons disease
Patients between 30 and 80 years of age with relatively advanced Parkinsons disease and dyskinesias due to levodopa therapy may be eligible for this 6-week study
Screening and baseline evaluation - Participants are evaluated with a medical history physical examination and neurologic evaluation blood tests urinalysis electrocardiogram EKG 24-hour holter monitor heart monitoring and cardiology consultation A chest x-ray and MRI or CT scan of the brain are done if needed If possible patients stop taking all antiparkinsonian medications except levodopa Sinemet for one month 2 months if taking Selegiline before the study begins and throughout its duration If necessary patients may use short-acting agents such as Mirapex Requip or Amantadine
Dose-finding phase - Patients are admitted to the NIH Clinical Center for 2 to 3 days for a levodopa dose-finding procedure For this test patients stop taking Sinemet and instead have levodopa infused through a vein During the infusions the drug dose is increased slowly until parkinsonian symptoms improve or unacceptable side effects occur or the maximum study dose is reached Symptoms are monitored frequently Patients who have had dosing infusions in the last 3 months do not have to undergo this phase of the study
Active study phase - Patients are randomly assigned to take levetiracetam or placebo sugar pill twice a day for 6 weeks At the end of weeks 1 2 4 and 5 patients come to the clinic for blood tests an EKG and a review of adverse side effects At the end of weeks 3 and 6 patients are hospitalized to study the response to treatment They again stop taking Sinemet and selegiline and their ability to perform motor tasks is evaluated They are then placed on an L-dopa infusion for 10 hours Placebo may be infused at various times instead of L-dopa Motor symptoms are evaluated several times during the infusion Blood is drawn once during the infusion for research studies
Lumbar puncture - Patients undergo a lumbar puncture spinal tap at the end of weeks 1 and 4 to measure certain brain chemicals and drug levels For this test a local anesthetic is given and a needle is inserted in the space between the vertebrae in the lower back About 2 tablespoons of fluid is collected through the needle
Magnetic resonance imaging MRI - Patients with changing disease activity may undergo MRIs at baseline at the end of week 1 and at the end of the study to show changes in the brain The patient lies in a narrow cylinder the scanner that uses radio waves and a magnetic field to produce images of the brain which show structural and chemical changes
Follow-up - 2 weeks after the study ends patients are contacted by phone for a review of side effects or they return to the clinic for an evaluation
Patients between 30 and 80 years of age with relatively advanced Parkinsons disease and dyskinesias due to levodopa therapy may be eligible for this 6-week study
Screening and baseline evaluation - Participants are evaluated with a medical history physical examination and neurologic evaluation blood tests urinalysis electrocardiogram EKG 24-hour holter monitor heart monitoring and cardiology consultation A chest x-ray and MRI or CT scan of the brain are done if needed If possible patients stop taking all antiparkinsonian medications except levodopa Sinemet for one month 2 months if taking Selegiline before the study begins and throughout its duration If necessary patients may use short-acting agents such as Mirapex Requip or Amantadine
Dose-finding phase - Patients are admitted to the NIH Clinical Center for 2 to 3 days for a levodopa dose-finding procedure For this test patients stop taking Sinemet and instead have levodopa infused through a vein During the infusions the drug dose is increased slowly until parkinsonian symptoms improve or unacceptable side effects occur or the maximum study dose is reached Symptoms are monitored frequently Patients who have had dosing infusions in the last 3 months do not have to undergo this phase of the study
Active study phase - Patients are randomly assigned to take levetiracetam or placebo sugar pill twice a day for 6 weeks At the end of weeks 1 2 4 and 5 patients come to the clinic for blood tests an EKG and a review of adverse side effects At the end of weeks 3 and 6 patients are hospitalized to study the response to treatment They again stop taking Sinemet and selegiline and their ability to perform motor tasks is evaluated They are then placed on an L-dopa infusion for 10 hours Placebo may be infused at various times instead of L-dopa Motor symptoms are evaluated several times during the infusion Blood is drawn once during the infusion for research studies
Lumbar puncture - Patients undergo a lumbar puncture spinal tap at the end of weeks 1 and 4 to measure certain brain chemicals and drug levels For this test a local anesthetic is given and a needle is inserted in the space between the vertebrae in the lower back About 2 tablespoons of fluid is collected through the needle
Magnetic resonance imaging MRI - Patients with changing disease activity may undergo MRIs at baseline at the end of week 1 and at the end of the study to show changes in the brain The patient lies in a narrow cylinder the scanner that uses radio waves and a magnetic field to produce images of the brain which show structural and chemical changes
Follow-up - 2 weeks after the study ends patients are contacted by phone for a review of side effects or they return to the clinic for an evaluation
Detailed Description:
Introduction Parkinsons disease is a progressive degenerative disease of unknown etiology Its treatment has been symptomatic and the most successful approach has been to replace the missing dopamine through administration of its precursor levodopa As the disease progresses the usefulness of this approach gradually diminishes and motor complications become a source of significant disability Although a number of pharmacological strategies have attempted to improve this situation none has yet proven fully satisfactory The mechanism by which levetiracetam exerts this beneficial effect is unknown Recently in a PD monkey model levetiracetam was found to moderate dyskinesias and other motor complications possibly due to its effects on striatal GABAergic transmission
Objective To evaluate the acute ability of levetiracetam to safely ameliorate dopaminomimetic-treatment-associated dyskinesias and related motor complications in parkinsonian patients without compromising the antiparkinsonian response
Study Population 22 moderately advanced parkinsonian patients will be enrolled into a randomized placebo controlled double-blind proof-of-principle study Levetiracetam efficacy will be assessed through the use of validated motor function scales Safety will be monitored by means of frequent clinical evaluations and laboratory tests
Anticipated Risks and Benefits The potential risks associated with this study amount to only a minor increase over minimal risk and are primarily associated with adverse reactions to the medications involved Levetiracetam is a marketed drug with a wide margin of safety Patients receiving drug could benefit from improvement of their symptoms those on placebo will also have their medications adjusted leading to an improved quality of life
Outcome Estimate and Potential Meaning for the Field This study should further the understanding of mechanisms contributing to motor disability in patients with PD that may lead to the development of improved therapeutic interventions for this disorder and for associated motor response complications
Objective To evaluate the acute ability of levetiracetam to safely ameliorate dopaminomimetic-treatment-associated dyskinesias and related motor complications in parkinsonian patients without compromising the antiparkinsonian response
Study Population 22 moderately advanced parkinsonian patients will be enrolled into a randomized placebo controlled double-blind proof-of-principle study Levetiracetam efficacy will be assessed through the use of validated motor function scales Safety will be monitored by means of frequent clinical evaluations and laboratory tests
Anticipated Risks and Benefits The potential risks associated with this study amount to only a minor increase over minimal risk and are primarily associated with adverse reactions to the medications involved Levetiracetam is a marketed drug with a wide margin of safety Patients receiving drug could benefit from improvement of their symptoms those on placebo will also have their medications adjusted leading to an improved quality of life
Outcome Estimate and Potential Meaning for the Field This study should further the understanding of mechanisms contributing to motor disability in patients with PD that may lead to the development of improved therapeutic interventions for this disorder and for associated motor response complications
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-N-0101 | None | None | None |