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

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)

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.

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: Minocycline, then Minocycline/Lovastatin; Drug: Lovastatin, then Minocycline/Lovastatin

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre de Recherche du CHUS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minocycline, then Minocycline/Lovastatin; Participants will take minocycline then a combined treatment of minocycline/lovastatin for 3 months.	Drug: Minocycline, then Minocycline/Lovastatin; 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.; Other Names: Minocin
Experimental: Lovastatin, then Minocycline/Lovastatin; Participants will lovastatin then a combined treatment of minocycline/lovastatin for 3 months	Drug: Lovastatin, then Minocycline/Lovastatin; 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.; Other Names: Mevacor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
(optional) Change in brain activity using Functional Magnetic Resonance Imaging (fMRI) at 8 and 20 weeks	fMRI is a non-invasive method of assessing brain activity by detecting signal changes in blood flow and oxygenation known as BOLD (Blood-Oxygen-Level Dependent) contrast imaging.	baseline, 8 weeks, 20 weeks
(optional) Change in neurochemistry using Transcranial Magnetic Stimulation (TMS) at 8 and 20 weeks	Using an unpainful magnetic stimulation on the primary motor cortex, TMS will be used to assess intracortical facilitation and inhibition, corresponding respectively to glutamate and GABAergic processes.	baseline, 8 weeks, 20 weeks

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Collaborators: FRAXA Research Foundation
• Investigators: Principal Investigator: François Corbin, MD/PhD, Fragile X Clinic, Centre de recherche du CHUS

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: January 25, 2016
• First Submitted That Met QC Criteria: February 10, 2016
• First Posted (Estimate): February 11, 2016

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Autism; Fragile X Syndrome; FMR1; FRAXA
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anti-Bacterial Agents; Lovastatin; L 647318; Dihydromevinolin; Minocycline
• Other Study ID Numbers: 2016-1177

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No