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

NCT02680379 | Completed Phase 2 DMC

• 1 other identifier: 2016-1177
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Fragile X Syndrome

Keywords

Fragile X Syndrome; Autism; FMR1; FRAXA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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 Outcomes (2)

• (optional) Change in brain activity using Functional Magnetic Resonance Imaging (fMRI) at 8 and 20 weeks

  baseline, 8 weeks, 20 weeks

• (optional) Change in neurochemistry using Transcranial Magnetic Stimulation (TMS) at 8 and 20 weeks

  baseline, 8 weeks, 20 weeks

Study Arms (2)

Minocycline, then Minocycline/Lovastatin

EXPERIMENTAL

Participants will take minocycline then a combined treatment of minocycline/lovastatin for 3 months.

Drug: Minocycline, then Minocycline/Lovastatin

Lovastatin, then Minocycline/Lovastatin

EXPERIMENTAL

Participants will lovastatin then a combined treatment of minocycline/lovastatin for 3 months

Drug: Lovastatin, then Minocycline/Lovastatin

Interventions

Minocycline, then Minocycline/Lovastatin DRUG

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.

Also known as: Minocin

Minocycline, then Minocycline/Lovastatin

Lovastatin, then Minocycline/Lovastatin DRUG

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.

Also known as: Mevacor

Lovastatin, then Minocycline/Lovastatin

Eligibility Criteria

• Age: 8 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Université de Sherbrooke: lead
• FRAXA Research Foundation: collaborator

Study Sites (1)

Centre de Recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (1)

• Morin-Parent F, Champigny C, Cote S, Mohamad T, Hasani SA, Caku A, Corbin F, Lepage JF. Neurophysiological effects of a combined treatment of lovastatin and minocycline in patients with fragile X syndrome: Ancillary results of the LOVAMIX randomized clinical trial. Autism Res. 2024 Sep;17(9):1944-1956. doi: 10.1002/aur.3222. Epub 2024 Sep 9.

  PMID: 39248107 DERIVED

Related Links

• Investigator profile

MeSH Terms

Conditions

Fragile X Syndrome; Autistic Disorder

Interventions

Minocycline; Lovastatin

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; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Naphthalenes

Study Officials

• François Corbin, MD/PhD

  Fragile X Clinic, Centre de recherche du CHUS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Francois Corbin, MD, PHD, FRCPC

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: February 11, 2016
• Study Start: March 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: November 1, 2017
• Last Updated: October 15, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)