COMMETS- Combination MCI Metabolic Syndrome

Rutgers The State University of New Jersey

Status and phase: Enrolling; Phase 2

Conditions: Alzheimer Disease; Mild Cognitive Impairment; Metabolic Syndrome

Treatments: Drug: Intranasal insulin; Drug: Semaglutide; Other: Intranasal insulin placebo; Other: Semaglutide placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06072963

Pro2023001136

Details and patient eligibility

About

The investigators propose a proof of concept RCT (randomized clinical trial), testing the efficacy of intranasal insulin (INI) with semaglutide, a combination therapy with strong biological plausibility to benefit impaired cognition through vascular mechanisms, in older adults with MetS (metabolic syndrome) and MCI (Mild Cognitive Impairment), who are enriched for cerebrovascular disease and at high dementia risk. The study will focus on cognitive and biological outcomes, allowing identification of relevant mechanisms.

Full description

The Specific Aims of the study are:

Aim 1. To examine the ease and precision of use of the intranasal device and once daily semaglutide pill.

Aim 2. To examine the adherence to the two types of treatment.

Aim 3. To examine the safety profile of the combination of intranasal insulin with semaglutide. The safety profile of each has been published broadly, but the safety of their combination has not been examined.

Aim 4. Although the primary goal of the pilot study is proof of concept essential to design a large combination therapy RCT, The investigators will compare the combination of intranasal insulin and semaglutide with the other three groups on a) cognition, b) cerebral blood flow (via ASL MRI), c) glucose uptake (via FDG PET), ADRD(Alzheimer's disease and related disorders)-related blood biomarkers (Aβ42/Aβ40 ratio, pTau181 and 231, NfL and GFAP), and expression of insulin signaling genes from brain derived exosomes.

Enrollment: 80 estimated patients

Sex: All

Ages: 60 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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80 participants in 4 patient groups, including a placebo group

Group 1

Experimental group

Description:

Will receive intranasal insulin therapy as well as Oral Semaglutide.

Treatment:

Drug: Intranasal insulin

Drug: Semaglutide

Group 2

Sham Comparator group

Description:

Will receive active intranasal insulin therapy and placebo Oral Semaglutide.

Treatment:

Other: Semaglutide placebo

Drug: Intranasal insulin

Group 3

Sham Comparator group

Description:

Will receive intranasal insulin placebo and active Oral Semaglutide .

Treatment:

Drug: Semaglutide

Other: Intranasal insulin placebo

Group 4

Placebo Comparator group

Description:

Will receive intranasal insulin placebo and Oral Semaglutide placebo.

Treatment:

Other: Semaglutide placebo

Other: Intranasal insulin placebo