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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by FRAXA Research Foundation.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Fragile X Research Foundation of Canada
Information provided by:
FRAXA Research Foundation
ClinicalTrials.gov Identifier:
NCT00858689
First received: March 9, 2009
Last updated: October 19, 2010
Last verified: October 2010

March 9, 2009
October 19, 2010
January 2009
November 2009   (final data collection date for primary outcome measure)
  • ABC Irritability subtest score [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • ABC Irritability subtest score [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • ABC Irritability subtest score [ Time Frame: 1 year ] [ Designated as safety issue: No ]
ABC Irritability subtest score [ Time Frame: Baseline, then at 8 weeks, with option for 1 year extension ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00858689 on ClinicalTrials.gov Archive Site
  • Parent Defined Target Symptoms Scale-Visual [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Clinical Global Impression Scale [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Stanford Binet 5 (SB5) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • The Peabody Picture Vocabulary Test Third Edition (PPVT-III) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Non-Verbal Associative Learning Task (NVALT) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Vineland Adaptive Behaviour Scales (VABS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Parent Defined Target Symptoms Scale-Visual [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Parent Defined Target Symptoms Scale-Visual [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Clinical Global Impression Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Clinical Global Impression Scale [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Stanford Binet 5 (SB5) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The Peabody Picture Vocabulary Test Third Edition (PPVT-III) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • The Peabody Picture Vocabulary Test Third Edition (PPVT-III) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Non-Verbal Associative Learning Task (NVALT) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Non-Verbal Associative Learning Task (NVALT) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Vineland Adaptive Behaviour Scales (VABS) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Vineland Adaptive Behaviour Scales (VABS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Parent Defined Target Symptoms Scale-Visual [ Time Frame: Baseline, then at 8 weeks, with option for 1 year extension ] [ Designated as safety issue: No ]
  • Clinical Global Impression Scale [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  • Stanford Binet 5 (SB5) [ Time Frame: Baseline, and at 1 year ] [ Designated as safety issue: No ]
  • The Peabody Picture Vocabulary Test Third Edition (PPVT-III) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  • The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  • Non-Verbal Associative Learning Task (NVALT) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  • Vineland Adaptive Behaviour Scales (VABS) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Add-on Pilot Trial of Minocycline to Treat Fragile X Syndrome
Add-on Pilot Trial of Minocycline in Fragile X Syndrome

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).

Fragile X Syndrome (FXS) is the most common known inherited form of mental impairment and is also associated with a range of learning disabilities, neurological problems, such as seizures, and behavioural difficulties. For many individuals with FXS, behavioural difficulties result in severe problems within the family and community, particularly in the form of agitation, temper outbursts, hyperactivity, and aggression. These problems often require a variety of psychopharmacological and behavioural approaches. Although a variety of medications can be helpful in FXS there are no targeted interventions based on molecular abnormalities that have been studied. Defects in dendritic spine formation have been found in the brains of patients with Fragile X, suggesting these structures may represent an anatomical and physiological basis for the cognitive deficits associated with this disorder. Recent research has suggested that minocycline may have a specific benefit in the treatment of FXS. Minocycline is an antibiotic that has been found to inhibit the activity of matrix metallo-proteinase-9 (MMP-9), which is up-regulated in the hippocampus of FMR1 KO mice and may be responsible for the immature dendritic spine profile of hippocampal neurons. Minocycline has recently been used to treat the FXS KO mouse model for Fragile X, and was found to rescue this abnormal phenotype by inducing the formation of mature dendritic spines in FMR1 KO hippocampal neurons, both in vitro and in vivo. Minocycline treated FXS KO mice also performed significantly better in the elevated maze, a cognitive performance test that measures activity and anxiety.

Exciting preclinical effects of minocycline with regard to the FXS disease model have led to this pilot proposal, which is designed to generate preliminary data that could be used to support a larger clinical trial.

The overall hypothesis is that minocycline is a specific molecular targeted treatment for FXS that will display beneficial effects on disruptive behaviour and possibly other associated features of FXS via a reduction in MMP-9 activity.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Fragile X Syndrome
Drug: Minocycline
50-100 mg PO BID for 8 weeks with an option for a 1 year extension.
Not Provided
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20
January 2010
November 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Both
13 Years to 35 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00858689
010308
No
Dr. Carlo Paribello, President, Medical Director, Fragile X Research Foundation of Canada
FRAXA Research Foundation
Fragile X Research Foundation of Canada
Principal Investigator: Carlo Paribello, M.D. Fragile X Research Foundation of Canada
FRAXA Research Foundation
October 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP