Efficacy of Levetiracetam in Oromandibular and Cranial Dystonia

Objectives:

--To determine the efficacy of levetiracetam (LVT) for reducing the symptoms of subjects
with oromandibular dystonia (OMD) or cranial dystonia (CD) as assessed by dystonia rating
scales and to report all adverse events in this study.

Sample Size and Population:

--We plan to recruit 10 subjects with either primary OMD or CD from the Movement Disorders
and Botulinum Toxin (BoNT) Clinics of HMCS.

Design:

--This is a randomized, double-blind placebo controlled cross-over study. All subjects will
receive a baseline evaluation and have their dystonia assessed by the eyes, mouth, speech
and swallowing subscores of the Burke-Fahn-Marsden (BFM) dystonia scale, and the eyes and
upper and lower face, jaw, and tongue subscores of the Global Dystonia Severity (GDS) rating
scale. They will then be randomized into two groups. Either LVT or placebo with a titration
schedule up to a total daily dose of 4000 mg will be prescribed for six weeks. After week 6,
all subjects will undergo tapering and a wash-out period (one week for tapering off and one
week for the washout). The two groups will then be switched to the opposite intervention
(LVT or placebo), following the same titration and tapering pattern. We will evaluate both
groups at weeks 3, 6, 11 and 14 using the same scales. This study requires six outpatient
visits to the NIH CC; the total duration of this study will be 15 weeks.

Outcome measurement:

Primary outcome: The percent change of sum of the eyes, mouth, speech and swallowing
subscores of BFM dystonia scale at weeks 6 and 14 comparing to the baseline.

Secondary outcome: The percent change of the sum of the eyes, mouth, speech and swallowing
subscores of BFM dystonia scale at weeks 3 and 11 and sum of eyes and upper face, lower face
and jaw and tongue subscores of the GDS rating scale at weeks 3, 6, 11 and 14 comparing to
baseline and all adverse events.

- INCLUSION CRITERIA FOR THE PARTICIPANTS:

1. Be at least 18 years of age and less than or equal to 80 years of age.

2. Must be able to provide consent.

3. Primary OMD or CD diagnosed by movement disorders specialist.

4. No history of receiving LVT.

5. If the subject is using other medications for their dystonia such as
anticholinergics, baclofen, benzodiazepines or tetrabenazine, the dosage must
stay the same starting 4 weeks before participation and throughout the duration
of the study. Subjects will also be prohibited from starting new medications for
their dystonia.

6. If the subject was injected with BoNT, the latest dose must be injected at least
12 weeks before participation in this study.

7. Subject is willing to not receive any BoNT injections during the entire study.

EXCLUSION CRITERIA FOR THE PARTICIPANTS:

1. Psychiatric co-morbidities such as depression, psychosis or phobic disorders.

2. Has had a history of brain tumor, stroke, documented history of peripheral trauma to
the mouth, jaw or face within a year from the onset of dystonia, epilepsy or
seizures.

3. Secondary OMD or CD.

4. Postural instability, frequent falling, severe vertigo or dizziness and severe
ataxia.

5. Inability to take medication via oral route due to severe degree of OMD.

6. An estimated creatinine clearance (eCrCL) less than 50 mL/min.

7. Pregnant, lactating or planning to become pregnant in 6 months. Women who are able to
get pregnant must be willing to use an effective method of contraception from the
time of enrollment until 3 months after the last dose of the study medication.