Escalating Doses of Memantine in Down Syndrome (MEDS-123)

Conditions

• Alzheimer Dementia (AD)
• Down Syndrome
• Intellectual Disability

Eligibility Criteria

Sex

ALL

Age

18 Years - 32 Years

Healthy Volunteers

Not accepted

Interventions

• Memantine — DRUG
  Escalating doses of Memantine: 20 mg/day; 40 mg/day; and potentially 60 mg/day (pending FDA approval after safety data review at the 40 mg/day dose level in the first 10 study participants).

Study Details

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.

Key Dates

First listed

Apr 15, 2026

Start date

Oct 1, 2026

Status verified

Sep 2026

Primary completion

May 31, 2028

Completion

May 31, 2028

Study Design

Enrollment

25 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Memantine
  Two escalating oral doses of Memantine will be administered (with a third dose of 60 mg/day that may be approved by the FDA, pending safety data to be collected at the 40 mg/day dose level in the first 10 study participants): 1) Memantine 10 mg, one tablet bid orally for nine weeks (including four-week standard dose titration protocol); 2) Memantine 10 mg, two tablets bid orally for nine weeks (including four-week dose titration); and potentially Memantine 10 mg, three tablets bid orally for nine weeks (pending FDA approval). This will be followed by a nine-week washout period and a single 20 mg oral dose of memantine to generate pharmacokinetic (PK) data.

Primary Outcome Measure

Safety and Tolerability (as measured by incidence of adverse events) [ Time Frame: 27 weeks for the first 10 participants and 36 weeks for the next 15 participants if the 60 mg/day-dose proves to be safe. ]

Central Contacts

• Melissa R Stasko, JD
  216-844-7281
  [email protected]
• Alberto C Costa, MD, PhD
  216-844-7395
  [email protected]

Locations (1)

Find similar trials in Cleveland, OH

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