Add-on Pilot Trial of Minocycline to Treat Fragile X Syndrome

NCT00858689 | Completed Results

• 1 other identifier: 010308
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Fragile X Syndrome (FXS) is the most common known inherited form of mental impairment, developmental disability and autism. Minocycline is an antibiotic that has recently been used to treat the mouse model for Fragile X, and was found to reverse the structural abnormalities that are seen their brain cells. The purpose of this research study is to determine if minocycline is an effective treatment for patients with fragile X syndrome (FXS).

Conditions

Fragile X Syndrome

Keywords

Clinical Drug Trial

Outcome Measures

Primary Outcomes (3)

• Change From Baseline of ABC Irritability Subtest Score at 8 Weeks

  The 15-item Irritability Scale includes questions about aggression, self-injury, tantrums, agitation, and unstable mood on a scale of 0 to 45 with higher scores indicating greater severity. This scale has been successfully used in previous medication studies in children with autism and in patients with FXS and in a controlled trial of ampakine CX516 in FXS. All ABC subscales showed good reliability when used by parents and caregivers of individuals with FXS to assess behavior in the CX516 study NCT00054730, and yielded intraclass correlation coefficient (ICC) values of 0.7-0.9.

  Baseline and 8 weeks

• ABC Irritability Subtest Score

  ABC Irritability subtest score was used

  8 weeks

• ABC Irritability Subtest Score

  ABC (Aberrant behavior checklist) Irritability subtest score was used

  1 year

Secondary Outcomes (20)

• Parent Defined Target Symptoms Scale-Visual

  Baseline

• Clinical Global Impression Scale

  Baseline

• Stanford Binet 5 (SB5)

  Baseline

• The Peabody Picture Vocabulary Test Third Edition (PPVT-III)

  Baseline

• The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  Baseline

Study Arms (1)

minocyline 50 mg or 100 mg PO BID

EXPERIMENTAL

open label treatment with minocycline low or high dose, 50 mg or 100 mg PO (by mouth) BID (twice a day), added to existing medication regimen for 8 weeks

Drug: Minocycline

Interventions

Minocycline DRUG

50-100 mg PO BID for 8 weeks with an option for a 1 year extension.

Also known as: Solodyn, Dynacin, Arestin, Minocin

minocyline 50 mg or 100 mg PO BID

Eligibility Criteria

• Age: 13 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of FXS by clinical evaluation and confirmed by FMR1-DNA testing with presence of full mutation or mosaicism for the full mutation. Prior DNA testing reports will be accepted, when available.
• Age between 13 to 35 years inclusive at the time of informed consent.
• Male or female
• CGI-Severity Score of 4 or greater, indicative of moderate or greater severity of behavioural problems. This is a 7-point scale of clinical global impression of severity that the clinician fills out after considering all the available information on the patient, including the parent history, the examination in clinic, reports from the school and other sources.
• Score of 9 or greater on the Aberrant Behaviour Checklist - Irritability Scale (top 50th %-tile). The ABC is a global behaviour checklist implemented for the measurement of drug and other treatment effects in mentally impaired individuals. It is made up of 5 empirically derived dimensions including irritability, lethargy/withdrawal, inappropriate speech, hyperactivity, and stereotypic behaviour based on 58 items that describe various behavioural problems.
• Availability of parent and/or caregiver for all clinic visits and assessments.
• English language fluency and reading level of 6th grade or greater in one caregiver.

You may not qualify if:

• Allergy to minocycline.
• Kidney disease or elevated renal function tests.
• Liver disease or elevated liver function tests.
• Participants with neutropenia, anemia, or thrombocytopenia.
• History of systemic lupus erythematosus or screening anti-nuclear antibody (ANA) titre of \>1:40, as minocycline may cause a lupus-like reaction.
• Individuals who do not have a mother or caregiver who is willing to participate in the clinic visits.
• Individuals who are pregnant or at risk to become pregnant, specifically sexually active females will be excluded.
• Presence of persistent psychotic symptoms
• Subjects with symptom severity likely judged to endanger personal safety or safety of others.
• History of systemic lupus erythematosus or screening anti-nuclear antibody (ANA) titre of \>1:40, as minocycline may cause a lupus-like reaction.

Sponsors & Collaborators

• FRAXA Research Foundation: lead
• Fragile X Research Foundation of Canada: collaborator

Study Sites (1)

Surrey Place Centre

Toronto, Ontario, M5S 2C2, Canada

Location

Related Publications (1)

• Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, Ethell DW. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol. 2010 Oct 11;10:91. doi: 10.1186/1471-2377-10-91.

  PMID: 20937127 RESULT

Related Links

• The Fragile X Research Foundation of Canada is a non-profit organization which is dedicated to funding biomedical research for improved treatment and, ultimately, a cure for fragile X.
• FRAXA is a non-profit organization whose mission is to accelerate progress toward effective treatments and a cure for Fragile X, by funding the most promising research.

MeSH Terms

Conditions

Fragile X Syndrome

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

This was an open-label trial. Further study in a randomized controlled trial is warranted.

Results Point of Contact

• Title: Michael R. Tranfaglia MD
• Organization: FRAXA Research Foundation

info@fraxa.org

978-462-1990

Study Officials

• Carlo Paribello, M.D.

  Fragile X Research Foundation of Canada

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2009
• First Posted: March 10, 2009
• Study Start: October 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: January 1, 2009
• Last Updated: February 18, 2016
• Results First Posted: February 18, 2016

Record last verified: 2016-02

Locations

CA (1)