Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Text Size

Trial of Minocycline to Treat Children With Fragile X Syndrome

This study has been completed.
Sponsor:
Collaborator:
The National Fragile X Foundation
Information provided by (Responsible Party):
Randi J. Hagerman, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT01053156
First received: January 19, 2010
Last updated: June 30, 2014
Last verified: June 2014
History of Changes
  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:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Clinical Global Impression Scale (CGI) [ Time Frame: 3 months (post first treatment) and 6 months (post second treatment) ] [ Designated as safety issue: No ]
    The CGI-I utilizes history from primary caregivers and incorporates it into a seven step clinical rating for follow up throughout treatment, from 1 "very much improved" to 7 "very much worse". Lower scores indicate more improvement. Scores were obtained post treatments. Scores from when the patients were on minocycline either first or second were combined and averaged to determine a least squares mean and placebo scores were obtained in the same manner.

  • Visual Analogue Scale- Behavior 1 [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the first behavior that the caregivers noted, out of three.


Secondary Outcome Measures:
  • Visual Analogue Scale- Behaviors 2 [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the second behavior that the caregivers noted, out of three.

  • Expressive Vocabulary Test-2 [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
    The EVT-2 standard score assesses language development through a participant's one word synonym response to visual stimuli. Standard scores range from 20-160. A standard score of 100 is average, with a 15 point standard deviation. Higher values represent a better outcome.

  • Vineland Adaptive Behavior Scale-II (VABS-II)Adaptive Behavior Composite Score [ Time Frame: Baseline, 3 months, and 6 months ] [ Designated as safety issue: No ]
    The VABS-II Adaptive Behavior Composite Score was used to assess adaptive skills. An Adaptive Behavior Composite Score may range from 20-160 with an average of 100 with a standard deviation of 15. Higher scores show improvement.

  • Aberrant Behavior Checklist-Community Edition (ABC-C)Composite Score [ Time Frame: Baseline, 3 months, and 6 months ] [ Designated as safety issue: No ]
    The ABC-C composite scores were used to quantify the severity of a patient's behaviors. A composite score consists of subscale scores including Irritability and Agitation, Lethargy and Social Withdrawal, Stereotypic Behavior, Hyperactivity and Noncompliance, and Inappropriate Speech. The composite score may range from 0-174. Lower scores indicate improvement.

  • Visual Analogue Scale Behavior 3- VAS3 [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the third behavior that caregivers noted, out of three.

  • VAS Categorized by Behavior: Aggression/ ADHD [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with aggression or ADHD behaviors.

  • VAS Categorized by Behavior:Anxiety/ Mood [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with anxiety or mood related behaviors.

  • VAS Categorized by Behavior:Language/ Cognition [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with language or cognitive symptoms.

  • VAS Categorized by Behavior: Other [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with other behaviors that were not able to be categorized.
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   (Child)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Publications:

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
Results First Received: February 8, 2013
Last Updated: June 30, 2014
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:
Syndrome
Fragile X Syndrome
Disease
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
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

ClinicalTrials.gov processed this record on September 23, 2016