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Efficacy of Levetiracetam in Oromandibular and Cranial Dystonia

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ClinicalTrials.gov Identifier: NCT02199509
Recruitment Status : Completed
First Posted : July 24, 2014
Results First Posted : July 11, 2017
Last Update Posted : July 11, 2017
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Other
Conditions Oromandibular Dystonia
Cranial Dystonia
Intervention Drug: Levetiracetam
Enrollment 8
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Levetiracetam Then Placebo Group Placebo Then Levetiracetam Group
Hide Arm/Group Description Patients with Primary Oromandibular Dystonia or Cervical Dystonia were given Levetiracetam at maximum tolerated dose for three weeks followed by a Placebo. Patients with Primary Oromandibular Dystonia or Cervical Dystonia were given Placebo for maximum dose for three weeks followed by Levetiracetam.
Period Title: Overall Study
Started 3 4
Completed 2 3
Not Completed 1 1
Reason Not Completed
Suicidal Ideation             0             1
Misunderstood titration schedule             1             0
Arm/Group Title Primary Oromandibular Dystonia or Cranial Dystonia
Hide Arm/Group Description All participants enrolled in the study.
Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants
65
(42 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
3
  60.0%
Male
2
  40.0%
1.Primary Outcome
Title Percent Change of the Sum of the Eyes, Mouth, Speech and Swallowing Subscores of the Burke-Fahn-Marsden (BFM) Dystonia Scale.
Hide Description 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.
Time Frame 6 and 14 weeks compared to baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Group Placebo Group
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: percent change
12.16  (29.07) 31.25  (26.86)
2.Secondary Outcome
Title Percent Change of the Sum of the Eyes, Mouth, Speech and Swallowing Subscores of Burke-Fahn-Marsten Dystonia Rating Scale (BFM)
Hide Description 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.
Time Frame 3 and 11 weeks compared to baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Group Placebo Group
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 5
Mean (Standard Deviation)
Unit of Measure: percent change
14.80  (55.76) 6.78  (29.37)
3.Secondary Outcome
Title Percent Change of the Sum of Eyes and Upper Face, Lower Face and Jaw and Tongue Subscores of the GDS Rating Scale
Hide Description 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
Time Frame 3, 6, 11 and 14 compared to baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levetiracetam Group at 3 or 11 Weeks Levetiracetam Group at 6 or 14 Weeks Placebo Group at 3 or 11 Weeks Placebo Group at 6 or 14 Weeks
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 5 5 5 5
Mean (Standard Deviation)
Unit of Measure: Percentage of change
-10.36  (20.06) 4.11  (32.31) -16.93  (36.49) -3.83  (24.80)
Time Frame 14 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Levetiracetam Placebo
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Levetiracetam Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Levetiracetam Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/5 (20.00%)      0/5 (0.00%)    
Psychiatric disorders     
Suicide Ideation *  1/5 (20.00%)  1 0/5 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Levetiracetam Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/5 (0.00%)    
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mark Hallett
Organization: National Institutes of Health
EMail: hallettm@ninds.nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT02199509     History of Changes
Other Study ID Numbers: 140152
14-N-0152
First Submitted: July 23, 2014
First Posted: July 24, 2014
Results First Submitted: March 28, 2017
Results First Posted: July 11, 2017
Last Update Posted: July 11, 2017