Minocycline in the Treatment of Angelman Syndrome

Brief Title

Minocycline in the Treatment of Angelman Syndrome

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

Detailed Description

      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

      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.

      Recruitment & Prescreening - We anticipate some of the study participants will live far from
      the study site. In order to reduce screen failures (travel to the site only to find out your
      child doesn't meet the study criteria) the following process is required. To give parents the
      opportunity to consider the study and have time to consult with their doctor(s), we will
      begin recruitment approximately one week after the study has been published on this website.
      Parents will be asked to submit their information electronically by clicking the link at the
      bottom of this webpage or by accessing weeberlab.com/clinical_trials.html. In the event they
      do not have internet access, they may call the study coordinator for assistance. Once you
      have indicated your interest in participation, a packet of information will be sent to you
      via email (or postal service if you prefer). The packet will include an informed consent
      document, a release of medical information and a form for your primary care doctor to
      complete and return directly to us. All of this information will be reviewed by the medical
      staff to determine your child's eligibility. Out of the first 50 eligible participants, 24
      will be randomly selected by the Clinical and Investigational Science Institute (CTSI) at

      Study Procedure - Those selected will be required to travel to the study site a total of 3
      times for 2 days each at their own expense (some assistance may be available through the
      Foundation for Angelman Syndrome Therapeutics, visit www.cureangelman.org). It is important
      that you seriously consider your ability to complete the study. The number of participants we
      are allowed to enroll is strictly governed and funding is limited. It is imperative data is
      collected from each of the 24 participants to ensure the best possible results. We do not
      know if your child will benefit from receiving this medication, which is why we are doing
      this study.

      During the visits your child will be asked to provide a blood sample and undergo an
      electroencephalogram gram (EEG), physical examination as well as behavioral assessments.
      During the first visit, the study drug, minocycline, will be dispensed to you. You will be
      asked to administer the study drug to your child twice daily. You will also be asked to log
      the administration to confirm compliance with the study regimen. A telephone interview will
      be conducted with you after 4 weeks of treatment to assess drug tolerance and to record any
      changes you may have observed. The study medication will be discontinued after 8 weeks of
      treatment. At the same time point, you will have to return to the study site for a follow up
      visit identical to the primary visit. The final follow up visit will occur at the 16 week
      time point (8 weeks following the minocycline treatment). This visit will be identical to the
      first two visits and will assess the lasting effects of the medication. Below is a summary of
      the study procedures.

      Summary of Study Procedures:

        1. Recruitment Begins - Interested parents contact the study staff via the internet form.

        2. Prescreening packets are sent - Informed Consent Document, Health Information Release &
           Primary Care Physician (PCP) questionnaire

        3. Eligibility Determined for 30 potential participants

        4. Random Selection of 24 participants

        5. Baseline Testing - Informed Consent Obtained, Lab work and EEG performed History and
           Physical exam performed

        6. Enrollment - Study Neurologist confirms the participant meets the study criteria.

        7. Behavioral Assessment

        8. Minocycline Administration

        9. Telephone Interview (4 weeks)

       10. Discontinue Minocycline (8 weeks)

       11. Follow up Assessment (8 weeks)

       12. Telephone Interview (12 weeks)

       13. Final Follow up assessment (16 weeks)

      At the bottom of the page you will find a link to the weeberlab.com/clinical_trials.html
      website. There you will be able to submit your contact information.

Study Type


Primary Outcome

A change from baseline in the Bayley Scales of Infant and Toddler Development, 2nd edition (BSID-II)Score

Secondary Outcome

 Normalization of the EEG (electroencephalogram) signature


Angelman Syndrome



Study Arms / Comparison Groups

 Children with Angelman Syndrome
Description:  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.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

April 2012

Completion Date

December 2014

Primary Completion Date

December 2014

Eligibility Criteria

        Inclusion Criteria:

          1. The participant is between the ages of 4 to 12 years old.

          2. The participant has been previously diagnosed with AS by clinical evaluation.

          3. The participant's diagnosis has molecular confirmation (e.g. karyotyping, fluorescent
             in situ hybridization (FISH), DNA methylation test or sequencing of the
             ubiquitin-protein ligase E3A gene) of the diagnosis.

          4. The participant has a CGI-Severity Score of at least 4 indicating a moderate level of
             behavioral difficulty.

          5. The participant is male or female.

          6. The participant has an acceptable surrogate capable of giving consent on the
             participant's behalf.

        Exclusion Criteria:

          1. The participant was diagnosed with AS with no identifiable molecular abnormality.

          2. The participant has a known allergy to MC or tetracycline.

          3. The participant is currently enrolled in a study in which a drug, vitamin or dietary
             manipulation is used in the treatment of AS.

          4. The participant suffers from severe or uncontrolled seizures or any other medical
             condition rendering the patient unstable.

          5. The participant suffers from cardiovascular, respiratory, liver, kidney or hematologic

          6. The participant suffers from liver disease or elevated liver function tests.

          7. The participant has a history of neutropenia, anemia or thrombocytopenia.

          8. The participant has a history of systemic lupus erythematosus or an anti-nuclear
             antibody (ANA) titer or >1:40.

          9. The participant is pregnant or at risk of becoming pregnant (sexually active females).

         10. The participant experiences persistent psychotic symptoms.

         11. The participant (or a parent/caregiver) is not willing to participate in clinic

         12. The participant experiences severe symptoms judged to likely to endanger the
             participant's safety or the safety of others.




4 Years - 12 Years

Accepts Healthy Volunteers



Edwin J Weeber, Ph.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

University of South Florida

Study Sponsor

Edwin J Weeber, Ph.D., Principal Investigator, University of South Florida

Verification Date

May 2014