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

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 Intervention Model: Crossover Assignment Masking: Participant, Care Provider, 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: fragile X syndrome

MedlinePlus related topics: Fragile X Syndrome

Drug Information available for: Minocycline Minocycline hydrochloride

Genetic and Rare Diseases Information Center resources: Fragile X Syndrome X-linked Mental Retardation and Macro-orchidism

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) ]
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.

Secondary Outcome Measures:

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.


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)
Sexes Eligible for Study:	All
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:

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.


Responsible Party:	University of California, Davis
ClinicalTrials.gov Identifier:	NCT01053156 History of Changes
Other Study ID Numbers:	200917522
Study First Received:	January 19, 2010
Results First Received:	February 8, 2013
Last Updated:	May 25, 2017

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 June 23, 2017