Phase 1B Trial on Escalating Doses of Memantine in Down Syndrome
University Hospitals Cleveland Medical Center
Summary
Down syndrome (DS) is typically caused by an extra chromosome 21 in the cell nucleus (trisomy 21, or T21). T21 is both the most common cause of genetically defined intellectual disability and the earliest documented cause of Alzheimer's disease (AD)-type pathology. Currently, all presymptomatic individuals with DS are classified as having 'Stage 0' DS-associated AD (DSAD). DSAD pathology evolves inexorably, with virtually all individuals with DS developing AD pathology by age 40, and approximately 50% meeting clinical dementia diagnosis criteria at 55 years of age. This study will test the hypothesis that the FDA-approved AD drug memantine, at higher-than-standard doses, may be effective as a cognitive enhancer in adolescents and young adults with DS. The primary goal of this phase 1b clinical trial will be the assessment of the safety and tolerability of three memantine doses in persons with DS. In addition, we will assess the effect of this drug on cognitive test scores and plasma biomarkers of AD in the study participants. Finally, we will also investigate steady-state plasma levels of memantine and the time course of memantine plasma levels after a single dose in the study participants (pharmacokinetics, or PK). The data generated through this phase 1b study will provide the essential safety, PK, and preliminary efficacy signals required to advance a phase 2 trial evaluating high-dose memantine as a first-in-class therapeutic strategy in DS.
Description
Based on preclinical evidence from mouse models of DS collected by our research team and others, we hypothesized over a decade ago that NMDA receptor dysfunction may play significant pathogenic roles in both the neurodevelopmental and the neurodegenerative components of DS. Four years ago, our research team published in the results of a two-site, randomized phase 2 trial of the AD drug memantine to investigate the safety, efficacy, and tolerability of this drug on cognitive and adaptive outcome measures in adolescents and young adults with DS. In this study, we found no evidence of cognitive-e…
Eligibility
- Age range
- 15–32 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Cytogenetically documented Trisomy 21 or Complete Unbalanced Translocation of Chromosome 21. Mosaic Trisomy 21 and partial translocations will be excluded from the study * No pregnancy by serum testing at screening. Females of child-bearing potential, sexually active must be practicing a reliable method of birth control. Urine pregnancy tests will be done at the 2 follow-up medical visits * Laboratory findings within normal limits or judged clinically insignificant at baseline * Vital signs within normal limits for age. Stable, medically treated hypotension will be allow…
Interventions
- DrugMemantine
Escalating doses of Memantine (20 mg/day; 40 mg/day; 60 mg/day)
Location
- University Hospitals Case Medical CenterCleveland, Ohio