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Trial of Minocycline to Treat Children With Fragile X Syndrome

Primary Purpose

Fragile X Syndrome

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
minocycline hydrochloride
Placebo
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fragile X Syndrome focused on measuring Fragile X syndrome, minocycline, targeted treatment

Eligibility Criteria

42 Months - 16 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M.I.N.D. Institute at University of California at Davis Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo pill

Minocycline

Arm Description

All patients will be on placebo for 3 months in this crossover study.

All patients will be on minocycline for 3 months in this crossover trial.

Outcomes

Primary Outcome Measures

Clinical Global Impression Scale (CGI)
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
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
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
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
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
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
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
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
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
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
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.

Full Information

First Posted
January 19, 2010
Last Updated
May 25, 2017
Sponsor
University of California, Davis
Collaborators
The National Fragile X Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01053156
Brief Title
Trial of Minocycline to Treat Children With Fragile X Syndrome
Official Title
Randomized Double-Blind Controlled Cross Over Trial of Minocycline in Children With Fragile X Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis
Collaborators
The National Fragile X Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fragile X Syndrome
Keywords
Fragile X syndrome, minocycline, targeted treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo pill
Arm Type
Placebo Comparator
Arm Description
All patients will be on placebo for 3 months in this crossover study.
Arm Title
Minocycline
Arm Type
Experimental
Arm Description
All patients will be on minocycline for 3 months in this crossover trial.
Intervention Type
Drug
Intervention Name(s)
minocycline hydrochloride
Intervention Description
Minocycline hydrochloride dosed orally once a day for 3 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be given daily for 3 months.
Primary Outcome Measure Information:
Title
Clinical Global Impression Scale (CGI)
Description
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.
Time Frame
3 months (post first treatment) and 6 months (post second treatment)
Title
Visual Analogue Scale- Behavior 1
Description
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.
Time Frame
Baseline, 3 months, 6 months
Secondary Outcome Measure Information:
Title
Visual Analogue Scale- Behaviors 2
Description
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.
Time Frame
Baseline, 3 months, 6 months
Title
Expressive Vocabulary Test-2
Description
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.
Time Frame
Baseline, 3 months and 6 months
Title
Vineland Adaptive Behavior Scale-II (VABS-II)Adaptive Behavior Composite Score
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Title
Aberrant Behavior Checklist-Community Edition (ABC-C)Composite Score
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Title
Visual Analogue Scale Behavior 3- VAS3
Description
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.
Time Frame
Baseline, 3 months, 6 months
Title
VAS Categorized by Behavior: Aggression/ ADHD
Description
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.
Time Frame
Baseline, 3 months, 6 months
Title
VAS Categorized by Behavior:Anxiety/ Mood
Description
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.
Time Frame
Baseline, 3 months, 6 months
Title
VAS Categorized by Behavior:Language/ Cognition
Description
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.
Time Frame
Baseline, 3 months, 6 months
Title
VAS Categorized by Behavior: Other
Description
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.
Time Frame
Baseline, 3 months, 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
42 Months
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Randi J Hagerman, MD
Organizational Affiliation
M.I.N.D. Institute at University of California at Davis, Sacramento CA
Official's Role
Principal Investigator
Facility Information:
Facility Name
M.I.N.D. Institute at University of California at Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18835858
Citation
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. doi: 10.1136/jmg.2008.061796. Epub 2008 Oct 3.
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Trial of Minocycline to Treat Children With Fragile X Syndrome

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