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Trial record 5 of 20 for:    "angelman syndrome"

A Trial of Levodopa in Angelman Syndrome

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ClinicalTrials.gov Identifier: NCT01281475
Recruitment Status : Completed
First Posted : January 24, 2011
Results First Posted : January 13, 2017
Last Update Posted : January 9, 2018
Sponsor:
Collaborators:
Rady Children's Hospital, San Diego
University of California, San Francisco
Baylor College of Medicine
Vanderbilt University Medical Center
Greenwood Genetic Center
Children's Hospital Medical Center, Cincinnati
Angelman Syndrome Foundation, Inc.
Information provided by (Responsible Party):
Wen-Hann Tan, Boston Children’s Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Angelman Syndrome
Interventions Drug: Levodopa
Drug: Placebo Oral Capsule
Enrollment 67

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Levodopa Placebo
Hide Arm/Group Description

Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa.

Levodopa/carbidopa: Levodopa/Carbidopa (4:1)

Dosages are based on levodopa.

Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

The placebo (in this study, microcellulose) is not expected to have any effect.
Period Title: Overall Study
Started 33 34
Completed 29 26
Not Completed 4 8
Arm/Group Title Levodopa Placebo Total
Hide Arm/Group Description

Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa.

Levodopa/carbidopa: Levodopa/Carbidopa (4:1)

Dosages are based on levodopa.

Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

The placebo (in this study, microcellulose) is not expected to have any effect.

It is also taken 3 times a day, just like Levodopa.

Total of all reporting groups
Overall Number of Baseline Participants 29 26 55
Hide Baseline Analysis Population Description
Only participants who completed the study were analyzed. Therefore all numbers in the Results section refer to the participants who completed the study.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 26 participants 55 participants
<=18 years
29
 100.0%
26
 100.0%
55
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: In the Levodopa group, 4 participants failed to complete the study; in the Placebo group, 8 participants failed to complete the study. None of these 12 participants could be analyzed further, so we do not have the breakdown of their gender and other measures.
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 29 participants 26 participants 55 participants
Female 13 12 25
Male 16 14 30
Developmental age - Bayley Cognitive  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 29 participants 26 participants 55 participants
19  (8) 18  (6) 19  (7)
Tremors   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 26 participants 55 participants
16
  55.2%
15
  57.7%
31
  56.4%
[1]
Measure Description: Presence of tremors at baseline
1.Primary Outcome
Title Bayley Cognitive Age Equivalent at 1 Year
Hide Description [Not Specified]
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levodopa Placebo
Hide Arm/Group Description:

Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa.

Levodopa/carbidopa: Levodopa/Carbidopa (4:1)

Dosages are based on levodopa.

Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

The placebo (in this study, microcellulose) is not expected to have any effect.

The placebo capsules are taken 3 times a day, just like the levodopa / carbidopa capsules

Overall Number of Participants Analyzed 29 26
Mean (Standard Deviation)
Unit of Measure: months
19  (7) 19  (8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Levodopa, Placebo
Comments We performed generalized estimating equations with an unstructured covariance matrix to account for inter-correlations within measurements on the same participant over time.
Type of Statistical Test Superiority
Comments We modeled each outcome variable as a function of treatment (ie, levodopa versus placebo), visit (ie, baseline vs. 12-month follow-up) and the treatment-by-visit interaction; the interaction term tests whether the effect of levodopa treatment over time is significantly greater than that of the placebo group.
Statistical Test of Hypothesis P-Value <0.05
Comments After Bonferonni correction for multiple comparisons
Method Generalized estimating equations
Comments [Not Specified]
2.Secondary Outcome
Title Presence of Tremors
Hide Description [Not Specified]
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Levodopa Placebo
Hide Arm/Group Description:

Levodopa is prescribed as a combination of levodopa/carbidopa (4:1) to reduce the peripheral side effects. The dosage used was 15 mg/kg/day in 3 divided doses.

Levodopa: Levodopa/Carbidopa (4:1)

Dosages are based on levodopa.

Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa, so it is not expected to have any effect.

Placebo Oral Capsule: The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa.

Overall Number of Participants Analyzed 29 26
Measure Type: Count of Participants
Unit of Measure: Participants
14
  48.3%
12
  46.2%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Levodopa Placebo
Hide Arm/Group Description

Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa.

Levodopa/carbidopa: Levodopa/Carbidopa (4:1)

Dosages are based on levodopa.

Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

The placebo (in this study, microcellulose) is not expected to have any effect.
All-Cause Mortality
Levodopa Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Levodopa Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/33 (9.09%)      1/34 (2.94%)    
Gastrointestinal disorders     
Vomiting  1/33 (3.03%)  1 0/34 (0.00%)  0
General disorders     
Fever  0/33 (0.00%)  0 1/34 (2.94%)  1
Nervous system disorders     
Seizure  2/33 (6.06%)  2 0/34 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Levodopa Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/33 (33.33%)      9/34 (26.47%)    
Nervous system disorders     
Seizures  11/33 (33.33%)  9/34 (26.47%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Wen-Hann Tan
Organization: Boston Children's Hospital
Phone: 617-355 6394
Responsible Party: Wen-Hann Tan, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT01281475     History of Changes
Other Study ID Numbers: 09-12-0610
3523 ( Other Grant/Funding Number: OOPD )
First Submitted: January 20, 2011
First Posted: January 24, 2011
Results First Submitted: August 6, 2016
Results First Posted: January 13, 2017
Last Update Posted: January 9, 2018