Levetiracetam Administration for the Management of Levodopa-Induced Dyskinesias in Parkinson's Disease

Levetiracetam Administration for the Management of Levodopa-Induced Dyskinesias in Parkinson's Disease: A Double-Blind,Placebo-Controlled, Crossover Trial

Levodopa-induced dyskinesias have been associated with irregular oscillatory discharge characteristics of basal ganglia. From the other hand, LEV which shares a different electrophysiologic profile than other antiepileptics, inhibits hyper-synchronization of abnormal neuronal firing in experimental models of epilepsy. LEV also reduces levodopa-induced dyskinesias in MPTP-lesioned macaques and modulates "priming phenomenon" which associated with long-term changes in synaptic function that can lead to dyskinesias in PD.

Study objectives :

• To evaluate the effects of levetiracetam (LEV) in two doses (500 and 1000mg) vs placebo on disabling dyskinesias that develop as result of long-term treatment with levodopa, occurring at the time of maximal clinical improvement in patients with Parkinson's disease (PD).
• To evaluate the safety of LEV in patients with PD and antiparkinsonian medication.

Study Overview

• Status: Unknown
• Conditions: Levodopa Induced Dyskinesia
• Intervention / Treatment: Drug: Levetiracetam; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 151-27
    • Department of Neurology, 1st Hospital of Social Security Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Diagnosis of PD will be according to the criteria of United Kingdom Parkinson's Disease Society Brain Bank.

Other inclusion criteria:

• Patients between ages 30 and 80
• Hoehn and Yahr stage of PD over IIb
• Levodopa-induced dyskinesias (LID) despite optimization of antiparkinsonian medication
• LID severity 2 on item 32 and duration 2 on item 33 of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV
• Patient is willing to adhere to protocol requirements as evidence by written informed consent

Exclusion Criteria:

• Patient has a history of any medical condition or clinically significant laboratory abnormalities that can subject them to unwarranted risk.
• Female patient is pregnant or breastfeeding or 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.
• Patient with ablative surgeries or DBS implantation electrodes for diseases of the basal ganglia.
• Patient has a low Mini-mental Examination MMSE score <25 or has a history of bipolar psychosis or schizophrenia.
• Patient is unwilling to sign an informed consent or to comply with protocol requirements.
• Patient is taking or has taken in the past month amantadine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; placebo	Drug: Placebo; Placebo tabl
Active Comparator: 1; 500mg levetiracetam for one week and 1000mg levetiracetam for one week	Drug: Levetiracetam; 500mg (2 tabl of 250) for one week and 1000mg (4 tabl of 250) for one week
Active Comparator: 3; After crossover arm 3 equals arm 1	Drug: Levetiracetam; 500mg (2 tabl of 250) for one week and 1000mg (4 tabl of 250) for one week
Placebo Comparator: 4; After crossover arm 4 equals arm 2	Drug: Placebo; Placebo tabl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change of "on with levodopa-induced dyskinesias (LID)" time from patient diaries	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent change of "on without dyskinesias" and "off" time from patient diaries. Changes in severity and duration of LID according to the UPDRS , Schwab & England scale and also Goetz dyskinesia scale after a levodopa challenge dose.	24 hours

Collaborators and Investigators

• Sponsor: 1st Hospital of Social Security Services
• Collaborators: UCB Pharma
• Investigators: Study Chair: Pantelis Stathis, MD, 1st Hospital of Social Security Services; Principal Investigator: Spiros Konitsiotis, MD, Department of Neurology, University of Ioannina; Principal Investigator: Vasilis Kyriakakis, MD, Department of Neurology, General Hospital of Lamia; Principal Investigator: Georgios Tagaris, MD, Department of Neurology, PGNA "Georgios Genimatas"; Principal Investigator: Kostas Papadopoulos, MD, Department of Neurology, Hospital of Mental Diseases of Tripolis

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Study Completion (Anticipated): October 1, 2007

Study Registration Dates

• First Submitted: February 14, 2006
• First Submitted That Met QC Criteria: February 14, 2006
• First Posted (Estimate): February 15, 2006

Study Record Updates

• Last Update Posted (Estimate): November 15, 2007
• Last Update Submitted That Met QC Criteria: November 14, 2007
• Last Verified: November 1, 2007

More Information

Terms related to this study

• Keywords: Parkinson's; Levetiracetam; Levodopa-induced dyskinesias
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Dyskinesias; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: VALID-PD