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| ID | Type | Description | Link |
|---|---|---|---|
| 14-N-0152 |
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Background:
- People with dystonia cannot control their muscle contractions. This disorder can affect different body areas. When it affects the face, tongue, and jaw, it is called oromandibular dystonia (OMD) or cranial dystonia (CD). Researchers want to find out if a drug that treats seizures may help people with this kind of dystonia.
Objective:
- To see if levetiracetam can improve symptoms of jaw or face dystonia.
Eligibility:
- Adults ages 18 to 80 years with OMD or CD.
Design:
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levetiracetam | Drug | Anticonvulsant |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change of the Sum of the Eyes, Mouth, Speech and Swallowing Subscores of the Burke-Fahn-Marsden (BFM) Dystonia Scale. | The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is a measure of dystonia severity. The scale consists of evaluation of nine body parts (eyes, mouth, speech, swallowing, neck, trunk, right arm, right leg, left arm and left leg). The severity and provoking factors for each part are rated using a 5-point scale. These range from 0 (indicating no dystonia) to 4 (indicating the presence of dystonia at rest). The primary outcome measure includes the sum of the eyes, mouth, speech and swallowing subscores and represents the percent change from baseline to either 6 weeks or 14 weeks (representing the end of the 3 week period at the maximum tolerated dose for Levetiracetam or Placebo). The total range for these combined sub scores is 0-16, with higher scores indicating more severe dystonia and 0 indicating absence of dystonia. | 6 and 14 weeks compared to baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change of the Sum of the Eyes, Mouth, Speech and Swallowing Subscores of Burke-Fahn-Marsten Dystonia Rating Scale (BFM) | The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is a measure of dystonia severity. The scale consists of evaluation of ten body parts (eyes, mouth, speech, swallowing, neck, trunk, right arm, right leg, left arm and left leg). The severity and provoking factors for each part are rated using a 5-point scale. These range from 0 (indicating no dystonia) to 4 (indicating the presence of dystonia at rest). The secondary outcome measure includes the sum of the eyes, mouth, speech and swallowing subscores and represents the percent change from baseline to either 3 weeks or 11 weeks (representing the end of the three week titration period up to the maximum tolerated dose for Levetiracetam or Placebo). The total range for these combined sub scores is 0-16, with higher scores indicating more severe dystonia and 0 indicating absence of dystonia. |
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INCLUSION CRITERIA FOR THE PARTICIPANTS:
EXCLUSION CRITERIA FOR THE PARTICIPANTS:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Hallett, M.D. | National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
Subjects were excluded if they had a history of depression, psychosis or phobic disorders. One subject was consented but did not participate due to abnormal laboratory finding noted during screening.
Participants between the ages of 18 and 80 with a diagnosis of primary oromandibular or cranial dystonia were recruited from the Movement Disorders and Botulinum Toxin Clinics at the National Institutes of Health and from the Dystonia Global Registry and Dystonia Medical Research Foundation.
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| ID | Title | Description |
|---|---|---|
| FG000 | Levetiracetam Then Placebo Group | Patients with Primary Oromandibular Dystonia or Cervical Dystonia were given Levetiracetam at maximum tolerated dose for three weeks followed by a Placebo. |
| FG001 | Placebo Then Levetiracetam Group | Patients with Primary Oromandibular Dystonia or Cervical Dystonia were given Placebo for maximum dose for three weeks followed by Levetiracetam. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Primary Oromandibular Dystonia or Cranial Dystonia | All participants enrolled in the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change of the Sum of the Eyes, Mouth, Speech and Swallowing Subscores of the Burke-Fahn-Marsden (BFM) Dystonia Scale. | The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is a measure of dystonia severity. The scale consists of evaluation of nine body parts (eyes, mouth, speech, swallowing, neck, trunk, right arm, right leg, left arm and left leg). The severity and provoking factors for each part are rated using a 5-point scale. These range from 0 (indicating no dystonia) to 4 (indicating the presence of dystonia at rest). The primary outcome measure includes the sum of the eyes, mouth, speech and swallowing subscores and represents the percent change from baseline to either 6 weeks or 14 weeks (representing the end of the 3 week period at the maximum tolerated dose for Levetiracetam or Placebo). The total range for these combined sub scores is 0-16, with higher scores indicating more severe dystonia and 0 indicating absence of dystonia. | Posted | Mean | Standard Deviation | percent change | 6 and 14 weeks compared to baseline |
|
14 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Levetiracetam | Subjects received a starting dose of 500 mg twice daily of levetiracetam. The dose was increased by 250 mg twice daily, every three days until the subject reached a total daily dose of 4000 mg (2000 mg twice daily). The titration took approximately three weeks. At the end of week three, subjects returned to NIH for evaluation. The evaluation included a neurological evaluation using the dystonia rating scales and evaluation of any adverse events including but not limited to depression, hallucination, suicidal ideation or psychosis. Subjects remained on the maximum tolerated dose for three weeks. They returned to NIH at week six for the same evaluation as week three, after which subjects were asked to discontinue the medication in a taper-off fashion over a period of a week and then remain off the medication for another week. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicide Ideation | Psychiatric disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mark Hallett | National Institutes of Health | hallettm@ninds.nih.gov |
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| ID | Term |
|---|---|
| D000077287 | Levetiracetam |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 |
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| 3 and 11 weeks compared to baseline |
| Percent Change of the Sum of Eyes and Upper Face, Lower Face and Jaw and Tongue Subscores of the GDS Rating Scale | The Global Dystonia Severity Scale provides a severity rating for ten body regions, i.e.,1) eyes and upper face, 2) lower face, 3) jaw and tongue, 4) larynx, 5) neck, 6) shoulder and proximal arm, 7) distal arm and hand including elbow, 8) pelvis and upper leg, 9) distal leg and foot, and 10) trunk. Each body area is rated from 0 to 10, with 0 representing no dystonia present in that body area and 10 representing severe dystonia. The secondary outcome measure includes the sum of the eyes and upper face, lower face and jaw and tongue subscores of the GDS rating scale and represents the percent change from baseline to either 3 and 6 weeks or 11 and 14 weeks (representing the end of the three week titration period (3 weeks and 11 weeks) and the post-3 week period (6 weeks and 14 weeks) at the maximum tolerated dose for Levetiracetam or Placebo). The total range of these combined sub scores is 0-30, with higher scores indicating more severe dystonia and 0 indicating absence of | 3, 6, 11 and 14 compared to baseline |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Levetiracetam Group |
Subjects received a starting dose of 500 mg twice daily of levetiracetam. The dose was increased by 250 mg twice daily, every three days until the subject reached a total daily dose of 4000 mg (2000 mg twice daily). The titration took approximately three weeks. At the end of week three, subjects returned to NIH for evaluation. The evaluation included a neurological evaluation using the dystonia rating scales and evaluation of any adverse events including but not limited to depression, hallucination, suicidal ideation or psychosis. Subjects remained on the maximum tolerated dose for three weeks. They returned to NIH at week six for the same evaluation as week three, after which subjects were asked to discontinue the medication in a taper-off fashion over a period of a week and then remain off the medication for another week. |
| OG001 | Placebo Group | Subjects received a starting dose of 500 mg twice daily of placebo. The dose was increased by 250 mg twice daily, every three days until the subject reached a total daily dose of 4000 mg (2000 mg twice daily). The titration took approximately three weeks. At the end of week three, subjects returned to NIH for evaluation. The evaluation included a neurological evaluation using the dystonia rating scales and evaluation of any adverse events including but not limited to depression, hallucination, suicidal ideation or psychosis. Subjects remained on the maximum tolerated dose for three weeks. They returned to NIH at week six for the same evaluation as week three, after which subjects were asked to discontinue the medication in a taper-off fashion over a period of a week and then remain off the medication for another week. |
|
|
| Secondary | Percent Change of the Sum of the Eyes, Mouth, Speech and Swallowing Subscores of Burke-Fahn-Marsten Dystonia Rating Scale (BFM) | The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is a measure of dystonia severity. The scale consists of evaluation of ten body parts (eyes, mouth, speech, swallowing, neck, trunk, right arm, right leg, left arm and left leg). The severity and provoking factors for each part are rated using a 5-point scale. These range from 0 (indicating no dystonia) to 4 (indicating the presence of dystonia at rest). The secondary outcome measure includes the sum of the eyes, mouth, speech and swallowing subscores and represents the percent change from baseline to either 3 weeks or 11 weeks (representing the end of the three week titration period up to the maximum tolerated dose for Levetiracetam or Placebo). The total range for these combined sub scores is 0-16, with higher scores indicating more severe dystonia and 0 indicating absence of dystonia. | Posted | Mean | Standard Deviation | percent change | 3 and 11 weeks compared to baseline |
|
|
|
| Secondary | Percent Change of the Sum of Eyes and Upper Face, Lower Face and Jaw and Tongue Subscores of the GDS Rating Scale | The Global Dystonia Severity Scale provides a severity rating for ten body regions, i.e.,1) eyes and upper face, 2) lower face, 3) jaw and tongue, 4) larynx, 5) neck, 6) shoulder and proximal arm, 7) distal arm and hand including elbow, 8) pelvis and upper leg, 9) distal leg and foot, and 10) trunk. Each body area is rated from 0 to 10, with 0 representing no dystonia present in that body area and 10 representing severe dystonia. The secondary outcome measure includes the sum of the eyes and upper face, lower face and jaw and tongue subscores of the GDS rating scale and represents the percent change from baseline to either 3 and 6 weeks or 11 and 14 weeks (representing the end of the three week titration period (3 weeks and 11 weeks) and the post-3 week period (6 weeks and 14 weeks) at the maximum tolerated dose for Levetiracetam or Placebo). The total range of these combined sub scores is 0-30, with higher scores indicating more severe dystonia and 0 indicating absence of | Posted | Mean | Standard Deviation | Percentage of change | 3, 6, 11 and 14 compared to baseline |
|
|
|
| 1 |
| 5 |
| 0 |
| 5 |
| EG001 | Placebo | Subjects received a starting dose of 500 mg twice daily of placebo. The dose was increased by 250 mg twice daily, every three days until the subject reached a total daily dose of 4000 mg (2000 mg twice daily). The titration took approximately three weeks. At the end of week three, subjects returned to NIH for evaluation. The evaluation included a neurological evaluation using the dystonia rating scales and evaluation of any adverse events including but not limited to depression, hallucination, suicidal ideation or psychosis. Subjects remained on the maximum tolerated dose for three weeks. They returned to NIH at week six for the same evaluation as week three, after which subjects were asked to discontinue the medication in a taper-off fashion over a period of a week and then remain off the medication for another week. | 0 | 5 | 0 | 5 |
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| Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |