Minocycline in the Treatment of Angelman Syndrome
There is mounting evidence to suggest that a treatment for Angelman syndrome is not just possible, but probable. The lack of known molecular targets associated with AS has hampered the development of specific therapeutics. However, a recent surge of potential therapeutics for other disorders associated with cognitive disruption has begun to be used in human clinical trials. The molecular modes of action for many of these new therapeutic agents have correlates to counter the molecular defects observed in AS. One such agent is minocycline (MC), a drug traditionally used as an antibiotic. This compound administered to a mouse model of AS showed a significant decrease in motor deficit and an increase in long term potentiation. The investigators believe a similar result will be observed when minocycline is administered to the AS patient and may lead to the development of an effective AS therapeutic.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Efficacy of Minocycline in the Treatment of Angelman Syndrome|
- A change from baseline in the Bayley Scales of Infant and Toddler Development, 2nd edition (BSID-II)Score [ Time Frame: Baseline, 8 weeks & 16 weeks ] [ Designated as safety issue: No ]The primary outcome measure consists of improvement in raw and standard scores on the Bayley Scales of Infant and Toddler Development when post Minocycline administration results are compared to baseline results.
- Normalization of the EEG (electroencephalogram) signature [ Time Frame: Baseline, 8 and 16 weeks ] [ Designated as safety issue: No ]The secondary outcome measures consist of normalization of the EEG signature when comparing post MC administration results to baseline results. Angelman syndrome patients have a characteristic EEG signature and are prone to seizure. It stands to reason then, if the administration of MC decreases the number of seizures, a difference in the EEG signature should be observed as well.
- A change from baseline in the Vineland Adaptive Behavior Scale, 4th edition (Vineland-II)Score [ Time Frame: Baseline, 8 and 16 weeks ] [ Designated as safety issue: No ]This test is to measure the adaptive behaviors; the ability to adapt to changes in one's environment, learn new everyday skills and level of independence.
- A change from baseline in the Aberrant Behavior Checklist - Community version (ABC - Community)Score [ Time Frame: Baseline, 8 and 16 weeks ] [ Designated as safety issue: No ]This behavior rating scale utilizes direct observation to measure behavior problems in those with mental retardation. The checklist evaluates irritability, lethargy, stereotypic behavior, hyperactivity, inappropriate speech and provides a raw score for each domain.
- A change from baseline in the Preschool Language Scale, Fourth Edition (PLS-4)Score [ Time Frame: Baseline, 8 and 16 weeks ] [ Designated as safety issue: No ]This test is used to evaluate the development of expressive and receptive language development. It also can be used to assess behaviors considered to be language precursors.
- A change from baseline in the Clinical Global Impressions Severity Scale Score [ Time Frame: Baseline, 8 & 16 weeks ] [ Designated as safety issue: No ]The CGI is a brief assessment used by the clinician to describe the participants condition before and after the administration of a study medication.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||May 2013|
|Estimated Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Experimental: Children with Angelman Syndrome
Children with a molecularly confirmed diagnosis of Angelman Syndrome meeting the protocol requirements will be selected randomly. All participants will receive the study drug, minocycline, over an identical time course. Participants will undergo identical baseline, 8 and 16 week follow up assessments.
The participant's parent or guardian will be instructed to administer minocycline caplets by mouth twice daily. Parents or guardians will be instructed to avoid dairy products, antacids, or any vitamin preparation that contains any divalent or trivalent cations (e.g. Aluminum, Calcium, Magnesium, etc.) for one hour prior to, and two hours after study medication administration.
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|United States, Florida|
|Univeristy of South Florida|
|Tampa, Florida, United States, 33613|
|Principal Investigator:||Edwin J Weeber, Ph.D.||University of South Florida|