Minocycline in the Treatment of Angelman Syndrome

NCT01531582 | Completed Results DMC

• 1 other identifier: WEEBER001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Angelman Syndrome

Keywords

Angelman; Minocycline; cognitive; children; tetracycline

Outcome Measures

Primary Outcomes (1)

• Bayley Scales of Infant and Toddler Development, 2nd Edition (BSID-II) Score at Baseline, 8 Weeks After Treatment, and at 16 Week Follow-up

  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. This is an individually administered test used to asses developmental functioning. The Bayley scales are typically used for ages 1-42 months, and can be utilized to identify developmental delay by evaluating five major areas of development: cognitive, communication, physical, social/emotional, and adaptive. The score ranges for each subscale are as follows: Cognitive, 0-91; Communication, 0-75; Receptive Language, 0-49; Expressive Language, 0-48; Gross Motor, 0-72; Fine Motor, 0-66; Self-Care, 0-72; and Self-Direction, 0-75. Fine and Gross Motor scores were summed for the Motor domain; Receptive and Expressive Language were combined for the Language domain. Increase in raw score indicates improvement in the specific subdomain for each of the listed scales.

  Baseline, 8 weeks & 16 weeks

Secondary Outcomes (4)

• Normalization of the EEG (Electroencephalogram) Signature

  Baseline, 8 and 16 weeks

• Vineland Adaptive Behavior Scale, 4th Edition (Vineland-II)Score at Baseline, 8 Weeks After Treatment, and at 16 Week Follow-up

  Baseline, 8 and 16 weeks

• Preschool Language Scale, Fourth Edition (PLS-4)Score at Baseline, 8 Weeks After Treatment, and at 16 Week Follow-up

  Baseline, 8 and 16 weeks

• Clinical Global Impressions Severity Scale Score at Baseline, 8 Weeks After Treatment, and at 16 Week Follow-up

  Baseline, 8 & 16 weeks

Study Arms (1)

Children with Angelman Syndrome

EXPERIMENTAL

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.

Drug: minocycline

Interventions

minocycline DRUG

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.

Also known as: Alti-Minocycline, Apo-Minocycline, Arestin, Dynacin, Gen-Minocycline, Klinomycin, Minociclina [INN-Spanish], Minocin, Minocyclin, Minocycline HCl, Minocyclinum [INN-Latin], Minocyn, Minomycin, Novo-Minocycline, Solodyn, Vectrin, Tetracycline

Children with Angelman Syndrome

Eligibility Criteria

• Age: 4 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The participant is between the ages of 4 to 12 years old.
• The participant has been previously diagnosed with AS by clinical evaluation.
• 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.
• The participant has a CGI-Severity Score of at least 4 indicating a moderate level of behavioral difficulty.
• The participant is male or female.
• The participant has an acceptable surrogate capable of giving consent on the participant's behalf.

You may not qualify if:

• The participant was diagnosed with AS with no identifiable molecular abnormality.
• The participant has a known allergy to MC or tetracycline.
• The participant is currently enrolled in a study in which a drug, vitamin or dietary manipulation is used in the treatment of AS.
• The participant suffers from severe or uncontrolled seizures or any other medical condition rendering the patient unstable.
• The participant suffers from cardiovascular, respiratory, liver, kidney or hematologic disease.
• The participant suffers from liver disease or elevated liver function tests.
• The participant has a history of neutropenia, anemia or thrombocytopenia.
• The participant has a history of systemic lupus erythematosus or an anti-nuclear antibody (ANA) titer or \>1:40.
• The participant is pregnant or at risk of becoming pregnant (sexually active females).
• The participant experiences persistent psychotic symptoms.
• The participant (or a parent/caregiver) is not willing to participate in clinic visits.
• The participant experiences severe symptoms judged to likely to endanger the participant's safety or the safety of others.

Sponsors & Collaborators

• University of South Florida: lead

Study Sites (1)

Univeristy of South Florida

Tampa, Florida, 33613, United States

Location

Related Publications (1)

• Grieco JC, Ciarlone SL, Gieron-Korthals M, Schoenberg MR, Smith AG, Philpot RM, Heussler HS, Banko JL, Weeber EJ. An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome. BMC Neurol. 2014 Dec 10;14:232. doi: 10.1186/s12883-014-0232-x.

  PMID: 25491305 DERIVED

Related Links

• If your interested in participating, click this link and submit your contact information.

MeSH Terms

Conditions

Angelman Syndrome; cyclopia sequence

Interventions

Minocycline; Tetracycline

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Edwin J. Weeber, Ph.D.
• Organization: University of South Florida, Morsani College of Medicine

eweeber@health.usf.edu

(813) 396-9995

Study Officials

• Edwin J Weeber, Ph.D.

  University of South Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2012
• First Posted: February 13, 2012
• Study Start: April 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: September 1, 2015
• Last Updated: April 18, 2023
• Results First Posted: April 18, 2023

Record last verified: 2015-11

Locations

US (1)