The Efficacy, Safety, And Tolerability Of Donepezil HCl (E2020) In Patients With CADASIL Who Have Cognitive Impairment

NCT00103948 | Completed Phase 2

• 2 other identifiers: E2020-A001-2332004-001162-40
• Study Type: interventional
• Target: 165
• Locations: 3 countries
• Sites: 4

Brief Summary

This is an 18-week, prospective, multi-center, randomized, double-blind, placebo-controlled, (1:1) parallel-group study.

Conditions

Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Cognitive function.

Interventions

Aricept DRUG

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range - Adult patients, 25 to 70 years of age inclusive
• Gender distribution - Men and women. -- Women of childbearing potential (\<1 year postmenopausal) must be practicing effective contraception and have a negative serum bHCG at Screening. Pregnant and/or lactating females are excluded. Patients who become pregnant during the study will be discontinued.
• Diagnostic evidence of CADASIL either by (1) identification of a NOTCH3 mutation (excluding polymorphisms) or (2) presence of typical deposits on an electron microscopy of a skin biopsy.
• Cognitive impairment - (1) Subjects or their study partners must give a description of cognitive problems and one of the following: (2a) MMSE score of 10-27 (inclusive) or (2b) Trails B score, 1.5 standard deviations below the mean after adjustment for age and education.

You may not qualify if:

• Race and ethnicity - Any race and ethnic group.
• Health - Generally healthy, ambulatory or ambulatory-aided (i.e., walker, cane or wheelchair) outpatient. Speech, motor function, comprehension, and corrected vision and hearing must be sufficient for compliance with all testing procedures.
• Clinical laboratory values must be within normal limits, or if abnormal, must be judged clinically insignificant by the Investigator/ physician.
• Patients with Vitamin B12 deficiency who are on a stable dose of medication for at least 12 weeks prior to Screening/Baseline and who have normal serum B12 levels at Screening/ Baseline will be eligible. Patients who might otherwise have been eligible can be re- screened when they meet this criterion. This stable dose of Vitamin B12 must be maintained throughout the study.
• Patients with hypothyroidism or hyperthyroidism who are on a stable dose of medication for at least 12 weeks prior to Screening, have a normal TSH and free T4 at screening, and are considered euthyroid will be eligible. Patients who might otherwise have been eligible can be re-screened when they meet this criterion. This stable dose must be maintained throughout the study.
• Patients must have a reliable study partner who has regular contact with the patient (e.g., an average of 4 or more contacts per week), can observe for possible adverse events, and can accompany the patient to all visits.
• Patients with a history of hypertension, cardiac disease, diabetes, or peripheral vascular disease, may be enrolled in the study provided that the following standards are met. -- Hypertension must be medication controlled (sitting SBP \< 175, sitting DBP \< 100 mm Hg) and cardiac disease (e.g., angina pectoris, congestive heart failure, right bundle branch block, or arrhythmias) is stable on appropriate medication for 12 weeks prior to Screening.
• Peripheral vascular disease must have been stable for 12 weeks prior to Screening. No elective surgical procedures should be planned during the course of the study (e.g., hernia repair and bunion removal). Patient with diabetes must be stable as demonstrated by an HbA1c of \<= 8.0% or a random serum glucose value of \<= 170 mg/dL.
• All patients with CADASIL are at risk for stroke/TIA and may be enrolled in the study provided that no new strokes have been diagnosed or identified to have occurred within the three months prior to Screening. Patients who might otherwise be eligible can be screened 12 weeks after the stroke. Patients with TIAs are eligible without a waiting period. Patients who are already enrolled will continue in the study as assessed by the Investigator/ physician.
• Patients with CADASIL may suffer depression. Such patients are eligible for enrollment if they are stable on medication for 12 weeks and have an MADRS score \< 20. Patients with an MADRS score \>= 20 may be re-screened after 12 weeks on a stable dose of medication. This stable dose must be maintained throughout the study.
• Minor medical conditions must be stable before study enrollment.
• Patients who are taking Gingko Biloba or Vitamin E and have been taking stable doses of these compounds for 8 weeks are allowed in the study. This stable dose must be maintained throughout the study.
• Neurological disorders affecting cognition or the ability to assess it that are not associated with CADASIL, such as Alzheimer's Disease, Parkinson's disease, normal pressure hydrocephalus, idiopathic seizure disorders, multiple sclerosis, cerebral vasculitis or infections of the central nervous system, subdural hematoma, as well as Human Immunodeficiency Virus (HIV) disease, a history of significant head trauma followed by persistent neurological deficits, sleep disorders affecting level of consciousness, or known structural brain abnormalities.
• Psychiatric disorders affecting the ability to assess cognition that are not typically associated with CADASIL, such as schizophrenia.
• Active drug or alcohol abuse or dependence in \<= 5 years by DSM-IV criteria.

Sponsors & Collaborators

• Eisai Limited: lead

Study Sites (4)

Jose Biller, M.D.

Maywood, Illinois, 60152, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Unknown Facility

Woodville, South Australia, 5011, Australia

Location

Unknown Facility

Málaga, 29010, Spain

Location

Related Publications (1)

• Dichgans M, Markus HS, Salloway S, Verkkoniemi A, Moline M, Wang Q, Posner H, Chabriat HS. Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL. Lancet Neurol. 2008 Apr;7(4):310-8. doi: 10.1016/S1474-4422(08)70046-2. Epub 2008 Feb 28.

  PMID: 18296124 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Margaret Moline, Ph.D.

  Eisai Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 17, 2005
• First Posted: February 18, 2005
• Study Start: February 1, 2005
• Primary Completion: October 1, 2006
• Study Completion: February 1, 2007
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

AU (1); US (2); ES (1)