RecruitingPhase 2

COMMETS- Combination MCI Metabolic Syndrome

Combination of Intranasal Insulin With Oral Semaglutide to Improve Cognition and Cerebral Blood Flow: a Feasibility Study

Lead sponsor

Rutgers, The State University of New Jersey

Assets

Insulin / Semaglutide

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criterion

•MoCA ≤27

Primary endpoints

•ADAS-Cog•Neuroimaging outcome -- The effect of the combination of Semaglutide

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 IDNCT06072963

Org study IDPro2023001136

Timeline

Milestones

Study first posted2023-10-10actual

Study start2024-01-30actual

Last update posted2024-03-22actual

Primary completion2027-12-01estimated

Study completion2028-12-01estimated

Assets

Drug assets

Insulin Semaglutide

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age60 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Diagnosis of MCI (based on a MOCA <27 and a clinical dementia rating scale [CDR] score of 0.5 representing questionable dementia).

•Diagnosis of MetS -requiring

a)abdominal obesity (waist circumference >102cm for men and >88cm for women), and

b)glucose intolerance (fasting glucose>110 mg/dL) and at least one of the following-c) dyslipidemia (high triglycerides [>150 mg/dL] and low HDL [<40mg/dL for men and <50 mg/dL for women]), or

d)elevated blood pressure (>130/>85 mmHg).

•Fluent in Hebrew

•The study requires an active study partner

Exclusion criteria

•Diabetes (of any type)

•Taking medications that may affect glucose metabolism (including a GLP-1RA).

•Diagnosis of dementia and its subtypes, conditions that may directly affect cognition,

•short life expectancy or a medical condition that precludes consistent participation in the study,

•contraindications to either insulin or Semaglutide.

•Medications that may affect glucose metabolism such as corticosteroids.

Endpoints (15)

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

Neuroimaging

Global cognition

Neurodegeneration biomarkers

Other (unclassified)

Function / daily living

Amyloid biomarkers

Tau biomarkers

Other clinical outcomes

Global cognition

3 endpoints

Primary/protocol endpoint

Cognitive change - The effect of the combination of Semaglutide and intranasal insulin on cognitive functioning.

Time frame:12 months

ADAS-Cog

categorical status, descriptive

Secondary/protocol endpoint

Change in specific cognitive domains - The effect of the combination of Semaglutide and intranasal insulin on executive functions and episodic memory.

Time frame:12 months

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Functional outcome - The effect of the combination of Semaglutide and intranasal insulin on functional performance.

Time frame:12 months

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Function / daily living

1 endpoint

Secondary/protocol endpoint

Functional outcome - The effect of the combination of Semaglutide with intranasal inulin on change in functional performance as measured by IADL (instrumental activities of daily living) questionnaires.

Time frame:12 months

change from baseline, improvement

Amyloid biomarkers

1 endpoint

Secondary/protocol endpoint

Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- Aβ.

Time frame:6 Months

change from baseline, improvement

Tau biomarkers

1 endpoint

Secondary/protocol endpoint

Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- T-tau.

Time frame:6 Months

change from baseline, improvement

Neurodegeneration biomarkers

2 endpoints

Secondary/protocol endpoint

Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- Neurofilament light (NfL).

Time frame:6 Months

Neurofilament light (NfL)

change from baseline, improvement

Secondary/protocol endpoint

Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- glial fibrillary acidic protein (GFAP).

Time frame:6 Months

change from baseline, improvement

Neuroimaging

4 endpoints

Primary/protocol endpoint

Neuroimaging outcome -- The effect of the combination of Semaglutide and intranasal insulin on cerebral blood flow (CBF).

Time frame:6 months

change from baseline, improvement

Primary/protocol endpoint

Neuroimaging outcome -- The effect of the combination of Semaglutide and intranasal insulin on brain glucose intake.

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Neuroimaging outcomes- The effect of the combination of Semaglutide and intranasal insulin on microstructural alterations indicative of tissue injury.

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Neuroimaging outcomes- The effect of the combination of Semaglutide and intranasal insulin on gray matter and hippocampal volume.

Time frame:6 months

change from baseline, improvement

Other clinical outcomes

1 endpoint

Secondary/protocol endpoint

Functional outcome - The effect of the combination of Semaglutide and intranasal insulin on physical capacity

Time frame:6 months

descriptive

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- P-tau181.

Time frame:6 Months

Phosphorylated tau 181 (p-tau181)

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers-P-tau231.

Time frame:6 Months

change from baseline, improvement

Publications (58)

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 dateJuly 21, 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 July 21, 2026 snapshot.