Randomized Controlled Study of Donepezil in Fragile X Syndrome
Condition: Fragile X Syndrome
MeSH terms: Fragile X Syndrome; Syndrome
Intervention: donepezil; sugar pill
Intervention description: donepezil (2.5 mg to 10.0 mg per day for 12 weeks); sugar pill (2.5 mg to 10.0 mg per day for 12 weeks)
Intervention MeSH terms: Donepezil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 45.0
Sex: All
Minimum age: 12 Years
Maximum age: 29 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. confirmed genetic diagnosis of fragile X syndrome

          2. age >=12, <=29

          3. Verbal IQ >= 50, <=75

          4. Tanner pubertal stage >= 3

        Exclusion Criteria:

          1. Current or lifetime DSM-IV diagnosis of bipolar disorder, schizophrenia,
             schizoaffective disorder, or psychotic disorder, NOS based upon reported history

          2. 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

          3. Concomitant or anticipated use of other medications having prominent effects on the
             cholinergic system (e.g., bethanechol, benztropine, atropine, succinylcholine)

          4. 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)

          5. Medical illnesses where donepezil could worsen the condition such as asthma, cardiac
             conduction abnormalities, urinary obstruction or gastrointestinal disease with gastric
             bleeding

          6. Pregnancy or sexually active females not using a reliable method of contraception

          7. 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.)