COMMETS- Combination MCI Metabolic Syndrome

What Was Tested

The trial (phase 2) is built around Semaglutide.

The study will focus on cognitive and biological outcomes, allowing identification of relevant mechanisms.

It had four arms (groups): Group 1 (experimental), Group 2 (sham comparator), Group 3 (sham comparator) and Group 4 (placebo comparator).

Will receive intranasal insulin therapy as well as Oral Semaglutide.

Will receive active intranasal insulin therapy and placebo Oral Semaglutide.

Will receive intranasal insulin placebo and active Oral Semaglutide .

The registry classes the interventions as drug and other.

More on the Plan

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.

To examine the adherence to the two types of treatment.

To examine the safety profile of the combination of intranasal insulin with semaglutide.

Who Took Part

80 planned participants were the target.

It was open to people of any sex aged from 60 years up to 90 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Diagnosis of MCI (based on a MOCA \<27 and a clinical dementia rating scale \[CDR\] score of 0.5 representing questionable dementia). Fluent in Hebrew. The study requires an active study partner.

The full record lists 4 inclusion and 6 exclusion criteria; among the exclusions: 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,.

How the Study Was Run

Design: randomized, crossover and quadruple-blind.

The participants were allocated by chance, so the Semaglutide group and the comparison group should start out alike.

In the crossover set-up each of the participants took both Semaglutide and the comparison in turn, acting as their own control.

Neither the participants nor the staff measuring them knew who was on Semaglutide, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2024-01-30 with completion listed for 2027-12-01.

It ran at 1 site in Israel.

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Cognitive change - The effect of the combination of Semaglutide and intranasal insulin on cognitive functioning (time frame: 12 months). Neuroimaging outcome -- The effect of the combination of Semaglutide and intranasal insulin on cerebral blood flow (CBF) (time frame: 6 months). Neuroimaging outcome -- The effect of the combination of Semaglutide and intranasal insulin on brain glucose intake (time frame: 6 months).

It also tracked 12 secondary outcomes, for example Neuroimaging outcomes- The effect of the combination of Semaglutide and intranasal insulin on gray matter and hippocampal volume, Functional outcome - The effect of the combination of Semaglutide and intranasal insulin on functional performance, Functional outcome - The effect of the combination of Semaglutide and intranasal insulin on physical capacity, Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- Aβ, Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers- P-tau181 and Neurobiological outcome - The effect of the combination of Semaglutide and intranasal insulin on ADRD-blood biomarkers-P-tau231.

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of Semaglutide in 80 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Semaglutide compound page, all human trials.