Randomized Controlled Study of Donepezil in Fragile X Syndrome

NCT01120626 | Completed Phase 2 Results DMC

• 6 other identifiers: SU-02042010-4923Autism Speaks 5907R34MH085899-01A1SPO#42922SPO#45612eProtocol 13773 (SQL 96239)
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Fragile X syndrome (FraX) is the most common known heritable cause of human intellectual disability. Though recent research has revealed much about the genetic and neurobiological bases of FraX, knowledge about specific and effective treatments for affected individuals is lacking. Based on information from both human and animal studies, one cause of intellectual disability in FraX may be related to deficits in a particular brain neurotransmitter system (the "cholinergic" system). Thus, the investigators propose to use a specific medication, donepezil, to augment cholinergic system in adolescents affected by FraX. If found to be effective, the knowledge generated by this research may also be relevant to other developmental disorders that share common disease pathways with FraX.

Conditions

Fragile X Syndrome

Outcome Measures

Primary Outcomes (1)

• Contingency Naming Test (CNT) Performance Score

  Week 12 Contingency Naming Test (CNT) performance score on Rule 2 (naming shapes) and on Rule 3 (If the inside shape matches the outside shape, name the color, otherwise, name the outside shape). Performance score is the number of correct responses per minute, calculated by dividing the number of correct responses by the time taken to complete the 27 items, and multiplying by 60. Higher scores indicate faster and more accurate responding.

  Week 12

Secondary Outcomes (1)

• Aberrant Behavior Checklist (ABC)

  Week 12

Study Arms (2)

donepezil

ACTIVE COMPARATOR

donepezil (2.5 mg to 10.0 mg per day for 12 weeks)

Drug: donepezil

sugar pill

PLACEBO COMPARATOR

sugar pill (2.5 mg to 10.0 mg per day for 12 weeks)

Drug: sugar pill

Interventions

donepezil DRUG

donepezil (2.5 mg to 10.0 mg per day for 12 weeks)

Also known as: Aricept

donepezil

sugar pill DRUG

sugar pill (2.5 mg to 10.0 mg per day for 12 weeks)

Also known as: lactose

sugar pill

Eligibility Criteria

• Age: 12 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• confirmed genetic diagnosis of fragile X syndrome
• age \>=12, \<=29
• Verbal IQ \>= 50, \<=75
• Tanner pubertal stage \>= 3

You may not qualify if:

• Current or lifetime DSM-IV diagnosis of bipolar disorder, schizophrenia, schizoaffective disorder, or psychotic disorder, NOS based upon reported history
• Poorly controlled seizure disorder or taking more than one anticonvulsant (subjects cannot be prescribed carbamazepine, phenytoin, or phenobarbital due to potential interaction effects with donepezil). The investigators will permit one anticonvulsant as monotherapy for seizures if the seizure disorder is well controlled with no evidence of break through seizures within the past year
• Concomitant or anticipated use of other medications having prominent effects on the cholinergic system (e.g., bethanechol, benztropine, atropine, succinylcholine)
• Medications or nutritional supplements that have the potential to significantly alter donepezil levels, clinical effects or adverse reactions (antifungal agents, corticosteroids, erythromycin, beta-blockers, calcium channel blockers, NSAIDs, gingko biloba, St. John's wort)
• Medical illnesses where donepezil could worsen the condition such as asthma, cardiac conduction abnormalities, urinary obstruction or gastrointestinal disease with gastric bleeding
• Pregnancy or sexually active females not using a reliable method of contraception
• If considering participation in brain MRI part of the study, then any contraindications for MRI (e.g., orthodontia, metal in or on the body, etc.)

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Mental Health (NIMH): collaborator
• Autism Speaks: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Links

• Center for Interdisciplinary Brain Sciences Research at Stanford

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

Donepezil; Sugars; Lactose

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

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Carbohydrates; Disaccharides; Oligosaccharides; Polysaccharides

Results Point of Contact

• Title: Allan Reiss, MD
• Organization: Stanford University

reiss@stanford.edu

650-498-4538

Study Officials

• Allan L Reiss

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: May 7, 2010
• First Posted: May 11, 2010
• Study Start: September 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 17, 2016
• Results First Posted: March 17, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)