Escalating Doses of Memantine in Down Syndrome (MEDS-123)
Starting soon · Phase 1
Conditions studied: Down Syndrome, Intellectual Disability
In brief
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 facts
- Study ID
- NCT07531940
- Run by
- University Hospitals Cleveland Medical Center
- People needed
- 25
- Starts
- 2026-06-01
- Expected to finish
- 2028-05-01
- Last updated by the study team
- 2026-05-11
Who can join
Age: 15 and older, up to 32. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- 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 allowed
- ECG must demonstrate predominately normal sinus rhythm. Minor abnormalities documented as clinically insignificant will be allowed
- Participants and their authorized representatives will provide written informed consent
- Participants who have received any experimental drug for Down syndrome must undergo a washout
- All participants must: Be in general good health as judged by the investigators; Be able to swallow oral medication; Have a reliable caregiver or family member who agrees to accompany participant to all visits, provide information about the participant as required by the protocol, and ensure compliance with the medication schedule; Be sufficiently proficient in English to reliably complete the study assessments
- Age and gender matching participants without Down syndrome, must be: Males or females without Down syndrome aged-matching (within 3 years) participants with Down syndrome whom they are expected to serve as controls
You may not qualify if…
- Participant weighing less than 40 kg
- Current psychiatric or neurologic diagnosis other than Down syndrome (e.g., major depressive disorder, schizophrenia, bipolar disorder, autism, Alzheimer disease)
- Current treatment with psychotropic drugs
- Drug or alcohol abuse or dependence
- Significant suicide risk or who would require treatment with electro-convulsive therapy or with psychotropic drugs during the study or who have received treatment with a depot neuroleptic drug within 6 months of entering the study.
- Current or expected (within the next 6 months) hospitalization or residence in a skilled nursing facility (may reside in group homes or other residential settings with no skilled nursing)
- Active or clinically significant conditions affecting absorption, distribution, or metabolism of study drug (e.g. inflammatory bowel disease or celiac disease)
- Significant allergies to or other significant intolerance of memantine therapy, its ingredients, or with contraindications to memantine therapy as stated in the prescribing information
- Participants who are expected to require general anesthetics during the course of the study
- Presence or recent history of seizure disorder (< 3 years).
- Clinically significant and/or clinically unstable systemic disease. (Those with controlled hypothyroidism must be on a stable dose of medication for at least 3 months prior to screening and have normal serum T-4 and TSH at screening; and those with controlled diabetes mellitus must have an HbA1c of < 8.0% and a random serum glucose value of < 170 mg/dl)
- Severe infections or a major surgical operation within 3 months prior to screening
- History of persistent cognitive deficits immediately following head trauma.
- Donation of blood or blood products less that 30 days prior to screening, while participating in the study, or four weeks after completion of the study
- Inability to comply with the protocol or perform the outcomes measures due to significant hearing or visual impairment or other issues judged relevant by the investigators
Where it is running
- University Hospitals Case Medical Center — Cleveland, Ohio, United States
Full record on ClinicalTrials.gov
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