Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00829439 |
|
Recruitment Status :
Completed
First Posted : January 27, 2009
Results First Posted : November 21, 2016
Last Update Posted : November 21, 2016
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
This study is designed to determine the highest dose of levodopa/carbidopa that can be tolerated without any serious side effects by children with Angelman syndrome.
It has been hypothesized that levodopa may lead to an improvement in the neurodevelopment and abnormal movements (e.g. tremors) in children with Angelman syndrome.
Data from this study will be used to design a phase II trial to determine the efficacy of levodopa in treating children with Angelman syndrome.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Angelman Syndrome | Drug: Levodopa/Carbidopa (4:1) | Phase 1 |
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. Animal studies have suggested that levodopa can reverse the excess phosphorylation of some enzymes involved in synaptic and neuronal function, including calcium/calmodulin-dependent kinase type 2 (CaMKII).
Recently, it was shown that excess phosphorylation of CaMKII may be responsible for some of the neurological deficits seen in Angelman syndrome. Therefore, it is hypothesized that levodopa may lead to an improvement in the neurodevelopment and abnormal movements (e.g. tremors) in children with Angelman syndrome.
Although many children have used levodopa for a variety of medical conditions over the last 30 years, it has not been approved by the Food and Drug Administration (FDA) for use in children, and it has not been formally studied in children with Angelman syndrome, so we do not know what dose of levodopa is most appropriate for children with Angelman syndrome.
Therefore, the purpose of this study is to find out the highest dose of levodopa that children with Angelman syndrome can tolerate without any serious side effects.
Once we know the dose of levodopa that can be tolerated by children with Angelman syndrome, we will conduct a larger follow-up study to find out whether levodopa will lead to an improvement in their development and tremor.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 16 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Dose-escalation Tolerability Study of Levodopa/Carbidopa in Angelman Syndrome |
| Study Start Date : | January 2009 |
| Actual Primary Completion Date : | June 2010 |
| Actual Study Completion Date : | June 2010 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Levodopa/Carbidopa
Other Names: Sinemet L-dopa Dosages are based on levodopa. Each cohort of 3 subjects will be placed on an increasing dose of levodopa (2, 5, 10, and 15 mg/kg/day) for 1 week, provided subjects in the preceding cohort tolerated the lower dose. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day. |
Drug: Levodopa/Carbidopa (4:1)
Dosages are based on levodopa. Each cohort of 3 subjects will be placed on an increasing dose of levodopa (2, 5, 10, and 15 mg/kg/day) for 1 week, provided subjects in the preceding cohort tolerated the lower dose. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day. Other Names:
|
- Maximum Dose of Levodopa/Carbidopa That Can be Tolerated (Without Any Dose Limiting Toxicity) by at Least 3 Subjects. [ Time Frame: 1 week ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 4 Years to 12 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Angelman syndrome, confirmed by molecular testing
- Must be willing to come for research visit on 2 days, exactly 1 week apart
Exclusion Criteria:
- On levodopa, carbidopa, or any dopamine agonists in the 2 weeks prior to participation
- Other medical conditions that may be associated with developmental or cognitive delays
- More than 2 clinical seizures per month
- Used monoamine oxidase (MAO) inhibitors within the last 2 weeks
- Used phenytoin within the last 2 weeks
- Used phenothiazines, butyrophenones, and thioxanthenes within last 2 weeks
- Hypersensitive to levodopa or carbidopa
- Cardiovascular disease or instability
- Respiratory diseases, including asthma, emphysema, chronic cough, and shortness of breath
- Liver disease
- Stomach or intestinal ulcers
- Kidney disease
- Hematological problems, including anemia, leucopenia, and thrombocytopenia
- Used investigational drugs/interventions within the past three months
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00829439
| United States, Massachusetts | |
| Children's Hospital Boston | |
| Boston, Massachusetts, United States, 02115 | |
| Principal Investigator: | Wen-Hann Tan, BMBS | Boston Children's Hospital |
| Responsible Party: | Wen-Hann Tan, Attending Physician in Genetics, Boston Children's Hospital |
| ClinicalTrials.gov Identifier: | NCT00829439 |
| Other Study ID Numbers: |
08-10-0490 |
| First Posted: | January 27, 2009 Key Record Dates |
| Results First Posted: | November 21, 2016 |
| Last Update Posted: | November 21, 2016 |
| Last Verified: | September 2016 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
|
Angelman syndrome Levodopa Carbidopa L-dopa |
|
Angelman Syndrome Syndrome Disease Pathologic Processes Movement Disorders Central Nervous System Diseases Nervous System Diseases Abnormalities, Multiple Congenital Abnormalities Chromosome Disorders Genetic Diseases, Inborn |
Levodopa Carbidopa Antiparkinson Agents Anti-Dyskinesia Agents Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Aromatic Amino Acid Decarboxylase Inhibitors Enzyme Inhibitors |