DyskinesiasPhase 2NCT00076674
Levetiracetam Treatment of L-dopa Induced Dyskinesias
A Phase 2 study testing Intravenous Levodopa in people with Dyskinesias and Parkinson Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will evaluate the effects of levetiracetam (Keppra (Trademark) on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Dyskinesias, Parkinson Disease
- What is being tested?
- Intravenous Levodopa
- Type of treatment
- Injection or infusion
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Oct 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients who meet all of the following inclusion criteria will be able to participate in the study:
- Patient is between the ages of 30 and 80, inclusive;
- Patient has been diagnosed with idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurological findings;
- Patient has relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations ;
- Patient is willing to adhere to protocol requirements as evidenced by written, informed consent.
Who cannot join
- Patients meeting any of the following exclusion criteria will not be enrolled or immediately withdrawn from the study, as appropriate:
- Patient has a history of any medical condition that can reasonably be expected to subject them to unwaranted risk;
- Patient has clinically significant laboratory abnormalities including impaired renal function (CL(cr) equals 30-50 ml/min.);
- Patient is uable to br treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist, such as pramipexole or ropinirole;
- Patient is taking a prohibited concomitant medication;
- Patient has not been using or was not continuing to use an adequate contraceptive method for the last 30 days, or is not at least one year post-menopausal (if female);
Show all 14Show fewer
- Patient is pregnant or breastfeeding;
- Patient is implanted with bilateral deep brain stimulators;
- Patient has prior pallidotomy or other ablative surgeries for treatment of PD;
- Patient has cognitive impairment (MMSE less than 25);
- Patient has participated in a clinical study with an investigational drug within the last 30 days;
- Patient has a condition (such as active drug or alcohol abuse) that, in the opinion of the investigators, would interfere with compliance or safety;
- Patient is unwilling to sign an informed consent or to comply with protocol requirements;
- Patient has a history of psychiatric illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
This study will evaluate the effects of levetiracetam (Keppra (Trademark) on Parkinson's 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 Parkinson's disease.
Patients between 30 and 80 years of age with relatively advanced Parkinson's disease and dyskinesias due to levodopa therapy may be eligible for this 6-week study.
Read more
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.
Read the detailed description
Introduction: Parkinson's 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.
- Conditions
- Dyskinesias, Parkinson Disease
- Being tested
- Intravenous Levodopa
- Keywords
- Parkinson's Disease, Keppra, Motor Fluctuations, Intravenous Levodopa, Antiparkinsonian Response, Parkinson Disease, PD
- Medical subject headings
- Dyskinesias, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous LevodopaDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2004 (estimated)
- Study startJan 2004
- Study completionOct 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DyskinesiasStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 40 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00076674
- Sponsor's protocol ID
- 040101
- Other IDs
- 04-N-0101
- Status last verified
- Oct 2005
- First submitted
- 28 Jan 2004
- Last updated
- 22 Sep 2016
- Results posted
- No
Publications
Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci. 1973 Dec;20(4):415-55. doi: 10.1016/0022-510x(73)90175-5. No abstract available.
PubMed 4272516Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med. 1988 Apr 7;318(14):876-80. doi: 10.1056/NEJM198804073181402.
PubMed 3352672Mizuno Y, Mori H, Kondo T. Parkinson's disease: from etiology to treatment. Intern Med. 1995 Nov;34(11):1045-54. doi: 10.2169/internalmedicine.34.1045.
PubMed 8774962
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levetiracetam Treatment of L-dopa Induced Dyskinesias
- ClinicalTrials.gov ID
- NCT00076674
- Acronym / sponsor ID
- 040101
- Conditions
- Dyskinesias, Parkinson Disease
- Keywords
- Parkinson's Disease, Keppra, Motor Fluctuations, Intravenous Levodopa, Antiparkinsonian Response, Parkinson Disease, PD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Jan 2004
- Study completion
- Oct 2005
- First posted
- 29 Jan 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effects of levetiracetam (Keppra (Trademark) on Parkinson's 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 Parkinson's disease.
Patients between 30 and 80 years of age with relatively advanced Parkinson's 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: Parkinson's 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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients who meet all of the following inclusion criteria will be able to participate in the study:
- Patient is between the ages of 30 and 80, inclusive;
- Patient has been diagnosed with idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurological findings;
- Patient has relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations ;
- Patient is willing to adhere to protocol requirements as evidenced by written, informed consent.
Key exclusion criteria (14 listed)
- Patients meeting any of the following exclusion criteria will not be enrolled or immediately withdrawn from the study, as appropriate:
- Patient has a history of any medical condition that can reasonably be expected to subject them to unwaranted risk;
- Patient has clinically significant laboratory abnormalities including impaired renal function (CL(cr) equals 30-50 ml/min.);
- Patient is uable to br treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist, such as pramipexole or ropinirole;
- Patient is taking a prohibited concomitant medication;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Levodopa | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2016.
- Background: PubMed 4272516Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci. 1973 Dec;20(4):415-55. doi: 10.1016/0022-510x(73)90175-5. No abstract available.
- Background: PubMed 3352672Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med. 1988 Apr 7;318(14):876-80. doi: 10.1056/NEJM198804073181402.
- Background: PubMed 8774962Mizuno Y, Mori H, Kondo T. Parkinson's disease: from etiology to treatment. Intern Med. 1995 Nov;34(11):1045-54. doi: 10.2169/internalmedicine.34.1045.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intravenous Levodopa in people with Dyskinesias and Parkinson Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00076674, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2016.