NCT06072963

COMMETS- Combination MCI Metabolic Syndrome

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Rutgers, The State University of New Jersey · Academic / Other
• Sex: All
• Age: 60 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Alzheimer Disease
• Mild Cognitive Impairment
• Metabolic Syndrome

Interventions

Type	Name	Description
DRUG	Semaglutide	The medication is available in 3, 7, and 14-mg tablets for oral use. Participants will be instructed to start with an initiating dose of 3 mg once daily. If they do not experience adverse events (nausea, vomiting, and abdominal pain) then the dose will be titrated to 7 mg once daily after 30 days. Again, if the participant does not experience adverse events, the dose will be further titrated after 30 days to 14 mg once daily. This does will continue until the end of the study, at 12 months.
DRUG	Intranasal insulin	The study will use the ViaNase; Kurve Technology intranasal device to administer insulin intra-nasally. This device has been used in other studies of persons with AD and has shown insulin penetration into the brain via CSF studies. Through sniffing, the medication crosses the blood-brain barrier (BBB) at the top of the nasal cavity. Participants will be instructed to press a switch that will turn on the device, engaging a pump that releases a nebulized stream of insulin through a nose piece into a nostril for 20 seconds (the device includes an electronic timer), after which the device switches off. The process is then repeated in the other nostril. The investigators decided on administration of 20IU of INI twice per day as the literature suggests this as the optimal dosage.
OTHER	Semaglutide placebo	Rybelsus semaglutide - this medicine will simulate taking the pill Rybelsus /semaglutide once a day. A pill identical to the medicine pill will be given.
OTHER	Intranasal insulin placebo	The placebo used in this study is saline. The investigators will administer saline, with exactly the same methods as the INI insulin (twice per day, 20 seconds each sniff, in each nostril.

Timeline

• Start date: 2024-01-30
• Primary completion: 2027-12-01
• Completion: 2028-12-01
• First posted: 2023-10-10
• Last updated: 2024-03-22

Locations

1 site across 1 country: Israel

Regulatory

• FDA-regulated drug study