Clinical Trial: Minocycline in the Treatment of Angelman Syndrome

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: The Efficacy of Minocycline in the Treatment of Angelman Syndrome

Brief Summary: 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.

Detailed Summary:

This prospective single arm cohort study is to be conducted at the University of South Florida. The study will examine the effect minocycline (MC) has on the traits of Angelman Syndrome.

Minocycline HCl is an FDA approved antimicrobial medication in the tetracycline family of drugs. Of all the tetracyclines, MC is the most lipid soluble and most active. Unlike other antibiotics in this family, MC possesses the unique characteristic of being able to cross the blood brain barrier. The study dosage has been used in other trial treatments of other neurologic disorders with positive outcomes. Studies of long-term administration of MC at the study dose have been shown to be safe and well tolerated. This dosage has already been approved by the FDA for use in the treatment of bacterial infections of multiple organ systems, and acne vulgaris.

It is important to note that minocycline is not approved to treat Angelman syndrome or to be used in children younger than 8 years old. The study protocol has been reviewed by several physicians and scientists and been deemed safe to proceed. As with any medication the potential for side effects exist. The side effects range from serious to mild and include allergic reactions to upset stomach. In order to minimize this risk, the medical staff will perform a thorough medical history and physical examination before the prescription is issued to ensure no allergy to this medication, penicillin or another tetracycline exists. Discoloration of the teeth is potential adverse effect that exists when taking high doses of MC over long periods of time. The tooth discoloration is permanent and the parent or guardian of the participants will be made aware of this potential side effect prior to enrollment in the study. In other studies using MC, the most common complaint was gastrointestinal upset.

Sponsor: University of South Florida

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Normalization of the EEG (electroencephalogram) signature [ Time Frame: Baseline, 8 and 16 weeks ]
  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 ]
  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 ]
  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 ]
  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 ]
  The CGI is a brief assessment used by the clinician to describe the participants condition before and after the administration of a study medication.

Original Secondary Outcome: Same as current

Information By: University of South Florida

Dates:
Date Received: February 5, 2012
Date Started: April 2012
Date Completion: December 2014
Last Updated: May 9, 2014
Last Verified: May 2014