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Not yet recruitingPhase 1

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

Phase 1B Trial on Escalating Doses of Memantine in Down Syndrome

Lead sponsor

University Hospitals Cleveland Medical Center

Asset

Memantine

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease

Key I/E criterion

•Study partner/caregiver required

Primary endpoint

•Safety and Tolerability

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07531940

Org study IDSTUDY20260078

Timeline

Milestones

Study first posted2026-04-15actual

Last update posted2026-10-05actual

Study start2026-10-14estimated

Primary completion2028-05estimated (month precision)

Study completion2028-05estimated (month precision)

Assets

Drug assets

Memantine

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age18 Years

Maximum age32 Years

SexAll

Healthy volunteersNot accepted

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.

•Vital signs within normal limits for age.

•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 DS must undergo a washout for a minimum of 5 half-lives of any experimental medications.

•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

Exclusion criteria

•Participant weighing less than 40 kg

•Current psychiatric or neurologic diagnosis other than Down syndrome (This includes, but is not limited to, major depressive disorder, schizophrenia, schizoaffective disorder, any other psychotic disorder, bipolar disorder, seizure disorder (no seizures for more than 3 years), autism, Down syndrome regression disorder, Alzheimer disease, Parkinson's disease, cerebrovascular disease, other dementias, brain tumor, or other known structural brain abnormalities.)

•Current treatment with psychotropic drugs.

•Drug or alcohol abuse or dependence within past 5 years.

•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.

•Use of NMDA receptor antagonists, such as amantadine (Symmetrel), ketamine, or dextromethorphan during the 30 days prior to screening.

•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.

•Unexplained alkaline urine conditions.

•Participants with severe renal impairment (i.e., estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2) will be excluded from the proposed clinical trial. The eGFR will be calculated using the eGFR Calculator from the National Kidney Foundation (https://www.kidney.org/professionals/gfr_calculator) using serum creatinine, age, sex, adjusted for body surface area (for medication-related decision making, using Dubois Method).

•Participants with severe hepatic impairment (Child-Pugh Category C) will also be excluded from the proposed clinical trial. Child-Pugh Category will be calculated using the MSD Professional Version online calculator (https://www.msdmanuals.com/professional/multimedia/clinical-calculator/child-pugh-classification-for-severity-of-liver-disease).

•History of persistent cognitive deficits immediately following head trauma. (Note: remote history of head trauma without cognitive sequelae is not an exclusion.)

•Cardiac QTc interval ≥ 480 ms.

•History or presence of encephalitis.

•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 (>40 dB hearing loss) or visual impairment (best corrected visual acuity of less than 20/60) or other clinically relevant issues, such as behavioral issues that may prevent full participation in the study.

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Memory

Other (unclassified)

Global cognition

Function / daily living

Amyloid biomarkers

Global cognition

1 endpoint

Other/protocol endpoint

Intellectual Functioning of the Participants as Assessed by Change in Score on the Matrices Subtest of the Differential Ability Scales-II (DAS-II)

Time frame:18 weeks for the first 10 participants and 27 weeks for the next 15 participants if the 60 mg/day-dose proves to be safe.

change from baseline, improvement

Memory

4 endpoints

Secondary/protocol endpoint

Efficacy of the Drug Memantine as Assessed by Change in Score on the California Verbal Learning Test-II (CVLT-II) Short Form Total Free Recall

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.

change from baseline, improvement

Secondary/protocol endpoint

Efficacy of the Drug Memantine as Assessed by Change in Score on the Recall of Digits Forward (From the Differential Ability Scales; DAS-II)

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.

change from baseline, improvement

Other/protocol endpoint

Exploratory Assessment of Change in Score on the Paired Associates Learning (PAL) From the Cambridge Neuropsychological Test Automated Battery (CANTAB)

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.

change from baseline, improvement

Other/protocol endpoint

Exploratory Assessment of Change in Score on the Pattern Recognition Memory (PRM; Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)

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.

change from baseline, improvement

Function / daily living

1 endpoint

Other/protocol endpoint

Adaptive/Behavioral Functioning of the Participants as Assessed by Change in Score on the Vineland Adaptive Behavior Scales, Third Edition (Vineland 3)

Time frame:18 weeks for the first 10 participants and 27 weeks for the next 15 participants if the 60 mg/day-dose proves to be safe.

change from baseline, improvement

Amyloid biomarkers

1 endpoint

Other/protocol endpoint

Measurement of plasma biomarkers of Alzheimer's disease

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.

Phosphorylated tau 217 (p-tau217)

change from baseline, improvement

Safety / tolerability / PK

5 endpoints

Primary/protocol endpoint

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.

event count, event

Other/protocol endpoint

Pharmacokinetics (PK): Maximum Plasma Concentration [Cmax]

Time frame:197 hours

concentration, descriptive

Other/protocol endpoint

Pharmacokinetics (PK): Time to Reach Cmax (Tmax)

Time frame:197 hours

time to event, event

Other/protocol endpoint

Pharmacokinetics (PK): Half-Life (T½)

Time frame:197 hours

concentration, descriptive

Other/protocol endpoint

Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC)

Time frame:197 hours

concentration, descriptive

Other (unclassified)

2 endpoints

Other/protocol endpoint/low confidence

Linguistic Functioning of the Participants as Assessed by Change in Score on the Test for Reception of Grammar 2nd Edition (TROG-II)

Time frame:18 weeks for the first 10 participants and 27 weeks for the next 15 participants if the 60 mg/day-dose proves to be safe.

change from baseline, improvement

Other/protocol endpoint/low confidence

Linguistic Functioning of the Participants as Assessed by Change in Score on the Peabody Picture Vocabulary Test-IV (PPVT-IV)

Time frame:18 weeks for the first 10 participants and 27 weeks for the next 15 participants if the 60 mg/day-dose proves to be safe.

change from baseline, improvement

Publications (24)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateNovember 5, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the November 5, 2026 snapshot.