Trial of Minocycline to Treat Children With Fragile X Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: minocycline hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 months (post first treatment) and 6 months (post second treatment)
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.	Baseline, 3 months, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 3 months, 6 months
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.	Baseline, 3 months and 6 months
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.	Baseline, 3 months, and 6 months
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.	Baseline, 3 months, and 6 months
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.	Baseline, 3 months, 6 months
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.	Baseline, 3 months, 6 months
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.	Baseline, 3 months, 6 months
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.	Baseline, 3 months, 6 months
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.	Baseline, 3 months, 6 months

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: 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

Publications and helpful links

General 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. doi: 10.1136/jmg.2008.061796. Epub 2008 Oct 3.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: January 19, 2010
• First Submitted That Met QC Criteria: January 20, 2010
• First Posted (ESTIMATE): January 21, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: minocycline; Fragile X syndrome; targeted treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: 200917522