Angelman SyndromePhase 2/3NCT01281475
A Trial of Levodopa in Angelman Syndrome
A Phase 2/3 study testing Levodopa in people with Angelman Syndrome, run by Wen-Hann Tan at 7 sites in United States.
Trial summary
This study is designed to determine whether levodopa will lead to an improvement in the development and tremor in children with Angelman syndrome (AS). It has been suggested that levodopa, a medication that is usually used to treat Parkinson disease in adults, may help children with AS in their overall development and… Read more about this study
- Who is it for?
- Ages 4 to 12 years
- Conditions the study is for
- Angelman Syndrome
- What is being tested?
- Levodopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 7 sitesUnited States
- Study dates
- Jan 2011to Jul 2015
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age between 4 years and 12 years (i.e., before the 13th birthday)
- Molecular confirmation of the diagnosis of AS, which may include abnormal methylation studies or UBE3A mutation analyses - only subjects with a molecular diagnosis will be allowed to enroll
- Not on LD, CD, or any dopamine agonists in the 2 weeks prior to participation
Who cannot join
- Co-morbid disorders that may be associated with developmental or cognitive delays
- Poorly controlled seizures - An average of more than 2 clinical seizures per month in the 12 months prior to enrollment.
- Use of medications that may interact with LD/CD including atypical antipsychotics (aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, risperidone, ziprasidone), monoamine oxidase inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine), or phenytoin within the last 14 days, or other investigational interventions within the past 3 months
- Presence of cardiovascular disease or instability, respiratory disease, liver disease, peptic ulcer disease, renal impairment, or hematological disorders
- Pregnancy
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Children's Hospital Boston
Boston, Massachusetts, 02115
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Greenwood Genetic Center
Greenwood, South Carolina, 29646
Baylor College of Medicine
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
Rady Children's Hospital, San Diego
San Diego, California, 92123
University of California, San Francisco
San Francisco, California, 94121
About this study
Official title: A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome
This study is designed to determine whether levodopa will lead to an improvement in the development and tremor in children with Angelman syndrome (AS).
It has been suggested that levodopa, a medication that is usually used to treat Parkinson disease in adults, may help children with AS in their overall development and reduce the tremor that some of them have.
If levodopa is found to be beneficial for children with AS, this could lead to a new treatment for AS.
Funding Source - FDA-OOPD
Read the detailed 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. 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.
Therefore, the purpose of this study is to find out whether levodopa will lead to an improvement in the development and in the tremor in children with AS.
- Conditions
- Angelman Syndrome
- Being tested
- Levodopa, Placebo Oral Capsule
- Keywords
- Angelman syndrome, Levodopa, Carbidopa, L-dopa
- Medical subject headings
- Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevodopaDrug
Also called Sinemet, L-dopa
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.
Placebo Oral CapsuleDrug
The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa.
| Study group | Role | What they receive |
|---|---|---|
| Levodopa | Experimental | 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. Receives: Drug: Levodopa |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bayley Cognitive Age Equivalent at 1 Year
Measured: 12 months
Secondary outcomes (1)
Presence of Tremors
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Angelman SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wen-Hann Tan
- Sponsor type
- University, hospital or other
- 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.
- Responsible party
- Sponsor-investigator, Wen-Hann Tan, Boston Children's Hospital
- Investigators
- Wen-Hann Tan, BMBS, Principal investigator, Boston Children's HospitalLynne M. Bird, MD, Principal investigator, Rady Children's Hospital, San DiegoSteven A. Skinner, MD, Principal investigator, Greenwood Genetic CenterCarlos A. Bacino, MD, Principal investigator, Baylor College of MedicineAnne Slavotinek, MD, Principal investigator, University of California, San FranciscoCary Fu, MD, Principal investigator, Vanderbilt University Medical CenterLogan Wink, M.D, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01281475
- Sponsor's protocol ID
- 09-12-0610
- Other IDs
- 3523
- Status last verified
- Jul 2020
- First submitted
- 20 Jan 2011
- Last updated
- 15 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome
- ClinicalTrials.gov ID
- NCT01281475
- Acronym / sponsor ID
- 09-12-0610
- Conditions
- Angelman Syndrome
- Keywords
- Angelman syndrome, Levodopa, Carbidopa, L-dopa
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Wen-Hann TanUniversity, hospital or other
- 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.
- Study start
- Jan 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 24 Jan 2011 (estimated)
- Results
- Posted 13 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to determine whether levodopa will lead to an improvement in the development and tremor in children with Angelman syndrome (AS).
It has been suggested that levodopa, a medication that is usually used to treat Parkinson disease in adults, may help children with AS in their overall development and reduce the tremor that some of them have.
If levodopa is found to be beneficial for children with AS, this could lead to a new treatment for AS.
Funding Source - FDA-OOPD
Detailed 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. 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.
Therefore, the purpose of this study is to find out whether levodopa will lead to an improvement in the development and in the tremor in children with AS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levodopa | Experimental | Drug: LevodopaLevodopa 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. |
| Placebo | Placebo comparator | Drug: Placebo Oral CapsuleThe 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. |
Who may qualify
- Ages
- 4 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Age between 4 years and 12 years (i.e., before the 13th birthday)
- Molecular confirmation of the diagnosis of AS, which may include abnormal methylation studies or UBE3A mutation analyses - only subjects with a molecular diagnosis will be allowed to enroll
- Not on LD, CD, or any dopamine agonists in the 2 weeks prior to participation
Key exclusion criteria (5 listed)
- Co-morbid disorders that may be associated with developmental or cognitive delays
- Poorly controlled seizures - An average of more than 2 clinical seizures per month in the 12 months prior to enrollment.
- Use of medications that may interact with LD/CD including atypical antipsychotics (aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, risperidone, ziprasidone), monoamine oxidase inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine), or phenytoin within the last 14 days, or other investigational interventions within the past 3 months
- Presence of cardiovascular disease or instability, respiratory disease, liver disease, peptic ulcer disease, renal impairment, or hematological disorders
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevodopaAlso: Sinemet, L-dopaLevodopa/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. | Drug | Levodopa |
| Placebo Oral CapsuleThe placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa. | Drug | Placebo |
Primary outcome
Bayley Cognitive Age Equivalent at 1 Year
Time frame: 12 months
1 secondary outcome
Presence of Tremors
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Angelman Syndrome
RecruitingPhase 3
BEACON - Phase III Clinical Study of Rugonersen in Angelman Syndrome.
Angelman Syndrome
RecruitingPhase 3
CHAMPION: A Study to Evaluate the Efficacy and Safety of Obudanersen (ION582) in Children and Adults With Angelman Syndrome (AS)
Angelman Syndrome
RecruitingObservational study
A Natural History Study of Angelman Syndrome
Angelman Syndrome, Neurodevelopmental Conditions
Active, not recruitingPhase 3
REVEAL: A Phase 3 Study of Obudanersen (ION582) in Angelman Syndrome
Angelman Syndrome
Active, not recruiting
Web Intervention for Parents of Youth With Genetic Syndromes (WINGS)
Telomeric 22Q13 Monosomy Syndrome, Tuberous Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wen-Hann Tan, BMBS principal investigator
Boston Children's Hospital
Lynne M. Bird, MD principal investigator
Rady Children's Hospital, San Diego
Steven A. Skinner, MD principal investigator
Greenwood Genetic Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Levodopa in people with Angelman Syndrome, run by Wen-Hann Tan at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bayley Cognitive Age Equivalent at 1 Year (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2020.