- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00858689
Add-on Pilot Trial of Minocycline to Treat Fragile X Syndrome
Add-on Pilot Trial of Minocycline in Fragile X Syndrome
Study Overview
Detailed Description
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, behavioral 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 (Fragile X Mental Retardation-1 Knockout) 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5S 2C2
- Surrey Place Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: minocyline 50 mg or 100 mg PO BID
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
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50-100 mg PO BID for 8 weeks with an option for a 1 year extension.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline of ABC Irritability Subtest Score at 8 Weeks
Time Frame: Baseline and 8 weeks
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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.
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Baseline and 8 weeks
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ABC Irritability Subtest Score
Time Frame: 8 weeks
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ABC Irritability subtest score was used
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8 weeks
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ABC Irritability Subtest Score
Time Frame: 1 year
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ABC (Aberrant behavior checklist) Irritability subtest score was used
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1 year
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Parent Defined Target Symptoms Scale-Visual
Time Frame: Baseline
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Baseline
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Clinical Global Impression Scale
Time Frame: Baseline
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Baseline
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Stanford Binet 5 (SB5)
Time Frame: Baseline
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Baseline
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The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Time Frame: Baseline
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Baseline
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The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time Frame: Baseline
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Baseline
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Non-Verbal Associative Learning Task (NVALT)
Time Frame: Baseline
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Baseline
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Vineland Adaptive Behaviour Scales (VABS)
Time Frame: Baseline
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Baseline
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Parent Defined Target Symptoms Scale-Visual
Time Frame: 8 weeks
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8 weeks
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Parent Defined Target Symptoms Scale-Visual
Time Frame: 1 year
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1 year
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Clinical Global Impression Scale
Time Frame: 8 weeks
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8 weeks
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Clinical Global Impression Scale
Time Frame: 1 year
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1 year
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Stanford Binet 5 (SB5)
Time Frame: 1 year
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1 year
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The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Time Frame: 8 weeks
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8 weeks
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The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Time Frame: 1 year
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1 year
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The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time Frame: 8 weeks
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8 weeks
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The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time Frame: 1 year
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1 year
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Non-Verbal Associative Learning Task (NVALT)
Time Frame: 8 weeks
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8 weeks
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Non-Verbal Associative Learning Task (NVALT)
Time Frame: 1 year
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1 year
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Vineland Adaptive Behaviour Scales (VABS)
Time Frame: 8 weeks
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8 weeks
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Vineland Adaptive Behaviour Scales (VABS)
Time Frame: 1 year
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1 year
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Carlo Paribello, M.D., Fragile X Research Foundation of Canada
Publications and helpful links
Helpful 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- 010308
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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