Trial of Minocycline to Treat Children With Fragile X Syndrome

NCT01053156 | Completed Results DMC

• 1 other identifier: 200917522
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Fragile X Syndrome

Keywords

Fragile X syndrome; minocycline; targeted treatment

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Visual Analogue Scale- Behaviors 2

  Baseline, 3 months, 6 months

• Expressive Vocabulary Test-2

  Baseline, 3 months and 6 months

• Vineland Adaptive Behavior Scale-II (VABS-II)Adaptive Behavior Composite Score

  Baseline, 3 months, and 6 months

• Aberrant Behavior Checklist-Community Edition (ABC-C)Composite Score

  Baseline, 3 months, and 6 months

• Visual Analogue Scale Behavior 3- VAS3

  Baseline, 3 months, 6 months

Study Arms (2)

Placebo pill

PLACEBO COMPARATOR

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

Drug: Placebo

Minocycline

EXPERIMENTAL

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

Drug: minocycline hydrochloride

Interventions

minocycline hydrochloride DRUG

Minocycline hydrochloride dosed orally once a day for 3 months.

Minocycline

Placebo DRUG

Placebo will be given daily for 3 months.

Placebo pill

Eligibility Criteria

• Age: 42 Months - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Must have fragile X syndrome with molecular documentation
• Current pharmacological treatment regimen has been stable for at least 4 weeks

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Davis: lead
• The National Fragile X Foundation: collaborator

Study Sites (1)

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

Sacramento, California, 95817, United States

Location

Related Publications (1)

• 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.

  PMID: 18835858 BACKGROUND

MeSH Terms

Conditions

Fragile X Syndrome; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding and preliminary efficacy analysis results known to investigators.

Results Point of Contact

• Title: Randi J. Hagerman MD, Medical Director of the MIND Institute
• Organization: MIND Institute, University of California Davis Medical Center

randi.hagerman@ucdmc.ucdavis.edu

916-703-0247

Study Officials

• Randi J Hagerman, MD

  M.I.N.D. Institute at University of California at Davis, Sacramento CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2010
• First Posted: January 21, 2010
• Study Start: January 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 30, 2017
• Results First Posted: July 30, 2014

Record last verified: 2017-05

Locations

US (1)