Clinical Trial: Trial of Minocycline to Treat Children With Fragile X Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Randomized Double-Blind Controlled Cross Over Trial of Minocycline in Children With Fragile X Syndrome

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: University of California, Davis

Current Primary Outcome:

  • Clinical Global Impression Scale (CGI) [ Time Frame: 3 months (post first treatment) and 6 months (post second treatment) ]
    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 ]
    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.


Original Primary Outcome: Clinical Global Impression Scale (CGI) [ Time Frame: Baseline, 3 months, and 6 months ]

Current Secondary Outcome:

  • Visual Analogue Scale- Behaviors 2 [ Time Frame: Baseline, 3 months, 6 months ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.


Original Secondary Outcome:

  • Visual Studies - Contrast detection protocol [ Time Frame: Baseline, 3 months and 6 months ]
  • Face Processing and Pupillometry protocol [ Time Frame: Baseline, 3 months, and 6 months ]
  • Visual Analogue [ Time Frame: Baseline, 3 months and 6 months ]
  • Clinical Global Impression Scale (CGI) [ Time Frame: Baseline, 3 months and 6 months ]
  • ADHD Rating Scale-IV [ Time Frame: Baseline, 3 months and 6 months ]
  • Kinder-Testbatterie zur Aufmerksamkeitsprüfung (KITAP) [ Time Frame: Baseline, 3 months and 6 months ]
  • Prepulse Inhibition protocol (PPI) [ Time Frame: Baseline, 3 months and 6 months ]
  • Expressive Vocabulary Test [ Time Frame: Baseline, 3 months and 6 months ]
  • Side Effect Scale [ Time Frame: 3 months and 6 months ]
  • Autism Diagnostic Observation Scale (ADOS) [ Time Frame: Baseline, 3 months, 6 months ]
  • Stanford Binet V or the Mullen Scales of Early Learning [ Time Frame: Baseline, 3 months, and 6 months ]
  • Vineland Adaptive Behavior Scale-II (VABS-II) [ Time Frame: Baseline, 3 months, and 6 months ]
  • Aberrant Behavior Checklist-Community Edition (ABC-C) [ Time Frame: Baseline, 3 months, and 6 months ]


Information By: University of California, Davis

Dates:
Date Received: January 19, 2010
Date Started: January 2010
Date Completion:
Last Updated: June 30, 2014
Last Verified: June 2014