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

1st Hospital of Social Security Services

Status and phase: Unknown; Phase 2

Conditions: Levodopa Induced Dyskinesia

Treatments: Drug: Placebo; Drug: Levetiracetam

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00291733

VALID-PD

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 30 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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50 participants in 4 patient groups, including a placebo group

1

Active Comparator group

Description:

500mg levetiracetam for one week and 1000mg levetiracetam for one week

Treatment:

Drug: Levetiracetam

2

Placebo Comparator group

Description:

placebo

Treatment:

Drug: Placebo

3

Active Comparator group

Description:

After crossover arm 3 equals arm 1

Treatment:

Drug: Levetiracetam

4

Placebo Comparator group

Description:

After crossover arm 4 equals arm 2

Treatment:

Drug: Placebo