Cognitive Impairment
Conditions
Brief summary
This is an 18-week, prospective, multi-center, randomized, double-blind, placebo-controlled, (1:1) parallel-group study.
Interventions
DRUGAricept
Sponsors
Eisai Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 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. * Head MRI - Evidence of disease consistent with CADASIL, and no evidence of another disease, which might account for cognitive impairment or dementia (as judged by the Investigator/physician at the site). (The latter may be determined with a CT head scan for eligibility purposes. The MRI would still be needed.) Must be obtained within 6 months of the Screening/Baseline visit. If no such head MRI had been previously obtained, a head MRI will be obtained as part of Screening/Baseline after all other inclusion and
Exclusion criteria
(except clinical laboratory determinations) are satisfied. Patients in whom an MRI is contraindicated can have a CT instead, however, MRI is the preferred modality. * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cognitive function. | — |
Countries
Australia, Spain, United States
Outcome results
None listed