RecruitingPhase 2NCT06072963

COMMETS- Combination MCI Metabolic Syndrome

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


Sponsor

Rutgers, The State University of New Jersey

Enrollment

80 participants

Start Date

Jan 30, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 60 YearsMax Age: 90 Years

Inclusion Criteria4

  • 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 Criteria6

  • 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.

Interventions

DRUGSemaglutide

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.

DRUGIntranasal 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.

OTHERSemaglutide 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.

OTHERIntranasal 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.


Locations(1)

Joseph Sagol Neuroscience center, Sheba Medical Center

Ramat Gan, Israel

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NCT06072963


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