Combined Treatment of Minocycline and Lovastatin to Treat Individuals With Fragile X Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Lovastatin, Minocycline and the combination Lovastatin/Minocycline are effective in treating behavioral symptoms in Fragile X individuals.

Official Title
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A Pilot Study Exploring the Safety and Synergistic Effect of a Minocycline/Lovastatin Combined Treatment on the Behavior of Individuals With Fragile X Syndrome; Validation of New Biochemical and Neurophysiological Markers (LovaMiX)

Conditions
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Fragile X Syndrome

Intervention / Treatment
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* Drug: Minocycline, then Minocycline/Lovastatin
* Drug: Lovastatin, then Minocycline/Lovastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Molecular diagnosis of fragile X syndrome The participant must be accompanied his parent, legal tutor or legal representative. Identify a caregiver who spends at least six hours per day with the participant (may be the parent, legal tutor, legal representative or an other person). IQ < 70 ABC-C score > 20 CGI-Severity score ≥ 4 Exclusion Criteria: Pregnant or breastfeeding participants Previous intolerance/allergy to statins, minocycline or tetracyclines Participants who have taken lovastatin or minocycline in the last 12 weeks Personal history of myopathy, myalgia or high creatine kinase (CK) levels Renal disease / liver disease / disturbed hepatorenal tests Participants taking more than three psychoactive medications (except anticonvulsants) Untreated or uncontrolled hypothyroidism Any other active medical condition Modification of psychoactive treatment in the last 6 weeks prior to randomization Participants under the age of 13 years who have incomplete formation of the crown of their teeth (except possibly their 3rd molars) as shown by panorex Concomitant use of prohibited drugs Prohibited drugs include other hypolipemic including gemfibrozil (or other fibrates) and niacin (nicotinic acid), angiotensin converting enzyme (ACE), cyclosporine, danazol, amiodarone, verapamil and inhibitors P450 (CYP3A4) (itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, inhibitors of HIV protease and nefazodone).

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline, then Minocycline/Lovastatin<br>Participants will take minocycline then a combined treatment of minocycline/lovastatin for 3 months. | Drug: Minocycline, then Minocycline/Lovastatin<br>* Participants of this group will take 1 tablet of minocycline 50mg daily for 4 weeks, minocycline 100mg for the following 4 weeks and finally a combined treatment of minocycline 100 mg and lovastatin 40mg for the following 12 weeks.<br>* Other names: Minocin;|
| Experimental: Lovastatin, then Minocycline/Lovastatin<br>Participants will lovastatin then a combined treatment of minocycline/lovastatin for 3 months | Drug: Lovastatin, then Minocycline/Lovastatin<br>* Participants of this group will take 1 tablet of lovastatin 20 mg daily for 4 weeks, lovastatin 40 mg for the following 4 weeks and finally a combined treatment of minocycline 100 mg and lovastatin 40 mg for the following 12 weeks.<br>* Other names: Mevacor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Aberrant Behavior Checklist-Community (ABC-C) total score at 8,12 and 20 weeks |  | baseline, 8 weeks, 12 weeks, 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression Scale improvement (CGI-I) |  | baseline, 8 weeks, 12 weeks, 20 weeks | 
| Change from baseline Social Responsiveness Scale (SRS) at 8 and 20 weeks |  | baseline, 8 weeks, 20 weeks | 
| Anxiety, depression and mood scale (ADAMS), change from baseline to 8 and 20 weeks |  | baseline, 8 weeks, 20 weeks | 
| Behavior Rating Inventory of Executive Function (BRIEF) |  | Before treatment and at the end of treatment (weeks 20) | 
| Change from baseline Vineland II; adaptive behaviour scale at 20 weeks |  | baseline, 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fragile X Syndrome, Autism, FMR1, FRAXA