Trial of Minocycline to Treat Children With Fragile X Syndrome - Full Text View

Sponsor:	University of California, Davis
Collaborator:	The National Fragile X Foundation
Information provided by (Responsible Party):	Randi J. Hagerman, MD, University of California, Davis
ClinicalTrials.gov Identifier:	NCT01053156

Purpose

This is a single center study at the UC Davis MIND Institute in patients age 3.5-16 years of age with fragile X syndrome (FXS), funded by a National Fragile X Foundation Grant. It is a controlled trial of minocycline, an antibiotic commonly used in children for infection or for treatment of neurodegenerative disorders. We are investigating its use in FXS because it lowers matrix metalloproteinase 9 (MMP9) levels, which are high in FXS, and it also strengthens brain connections in the animal models of FXS. We hypothesize that minocycline will likely be helpful for language, behavior and/or cognition in fragile X patients.

Condition	Intervention
Fragile X Syndrome	Drug: minocycline hydrochloride Drug: Placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Randomized Double-Blind Controlled Cross Over Trial of Minocycline in Children With Fragile X Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: 17q21.31 microdeletion syndrome MECP2 duplication syndrome PPM-X syndrome tetrasomy 18p

MedlinePlus related topics: Fragile X Syndrome

Drug Information available for: Minocycline Minocycline hydrochloride

U.S. FDA Resources

Further study details as provided by University of California, Davis:

Primary Outcome Measures:

Clinical Global Impression Scale (CGI) [ Time Frame: Baseline, 3 months, and 6 months ] [ Designated as safety issue: No ]
Visual Analogue [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Visual Studies - Contrast detection protocol [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
Face Processing and Pupillometry protocol [ Time Frame: Baseline, 3 months, and 6 months ] [ Designated as safety issue: No ]
Clinical Global Impression Scale (CGI) [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
ADHD Rating Scale-IV [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
Kinder-Testbatterie zur Aufmerksamkeitsprüfung (KITAP) [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
Prepulse Inhibition protocol (PPI) [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
Expressive Vocabulary Test [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
Side Effect Scale [ Time Frame: 3 months and 6 months ] [ Designated as safety issue: Yes ]
Autism Diagnostic Observation Scale (ADOS) [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
Stanford Binet V or the Mullen Scales of Early Learning [ Time Frame: Baseline, 3 months, and 6 months ] [ Designated as safety issue: No ]
Vineland Adaptive Behavior Scale-II (VABS-II) [ Time Frame: Baseline, 3 months, and 6 months ] [ Designated as safety issue: No ]
Aberrant Behavior Checklist-Community Edition (ABC-C) [ Time Frame: Baseline, 3 months, and 6 months ] [ Designated as safety issue: No ]

Enrollment:	66
Study Start Date:	January 2010
Study Completion Date:	December 2011
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo pill All patients will be on placebo for 3 months in this crossover study.	Drug: Placebo Placebo will be given daily for 3 months.
Experimental: Minocycline All patients will be on minocycline for 3 months in this crossover trial.	Drug: minocycline hydrochloride Minocycline hydrochloride dosed orally once a day for 3 months.

Detailed Description:

This is a single center study at the UC Davis MIND Institute in patients age 3.5-16 years of age with fragile X syndrome (FXS), funded by a National Fragile X Foundation Grant. It is a controlled trial of minocycline, an antibiotic commonly used in children for infection or for treatment of neurodegenerative disorders. We are investigating its use in FXS because it lowers matrix metalloproteinase 9 (MMP9) levels, which are high in FXS, and it also strengthens brain connections in the animal models of FXS. We hypothesize that minocycline will likely be helpful for language, behavior and/or cognition in fragile X patients.

The aim of this study is to carry out a double-blind placebo controlled trial of minocycline treatment in children with FXS who are 3.5 to 16 years of age. At baseline, we will assess behavior and perceptual and cognitive development. After the children have been treated for 3 months with either minocycline or placebo, they undergo the same baseline testing. They will then cross over and be treated for a second 3 months. We will carry out testing again at the end of the second 3 month period. We will also assess the side effects of minocycline treatment throughout the study.

Eligibility

Ages Eligible for Study:	42 Months to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Must have fragile X syndrome with molecular documentation
Current pharmacological treatment regimen has been stable for at least 4 weeks

Exclusion Criteria:

Subjects who plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study
subjects who are unable to take oral medication
subjects who have been on minocycline previously
subjects who are allergic to minocycline or tetracyclines
subjects who are pregnant
subjects with history of lupus or hepatic dysfunction

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01053156

Locations

United States, California
M.I.N.D. Institute at University of California at Davis Medical Center
Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

The National Fragile X Foundation

Investigators

Principal Investigator:

Randi J Hagerman, MD

M.I.N.D. Institute at University of California at Davis, Sacramento CA

More Information

Additional Information:

Fragile X Research and Treatment Center at the M.I.N.D. Institute at the University of California at Davis Medical Center This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

Bilousova TV, Dansie L, Ngo M, Aye J, Charles JR, Ethell DW, Ethell IM. Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet. 2009 Feb;46(2):94-102. Epub 2008 Oct 3.

Responsible Party:	Randi J. Hagerman, MD, Professor of Pediatrics, Medical Director of MIND Institute, University of California, Davis
ClinicalTrials.gov Identifier:	NCT01053156 History of Changes
Other Study ID Numbers:	200917522-1
Study First Received:	January 19, 2010
Last Updated:	April 10, 2012
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by University of California, Davis:

Fragile X syndrome
minocycline
targeted treatment

Additional relevant MeSH terms:

Fragile X Syndrome
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities

Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2012