Health TrialsbyHealthPanel

COMMETS- Combination MCI Metabolic Syndrome

ConditionsAlzheimer DiseaseMild Cognitive ImpairmentMetabolic Syndrome
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age60-90
SponsorRutgers, The State University of New Jersey

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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,

Trial design

Design model

Crossover

Treatments tested in this trial

  • Semaglutide

    Drug

    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.

  • Intranasal insulin

    Drug

    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.

  • Semaglutide placebo

    Other intervention

    Rybelsus semaglutide - this medicine will simulate taking the pill Rybelsus /semaglutide once a day. A pill identical to the medicine pill will be given.

  • Intranasal insulin placebo

    Other intervention

    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.

Treatment groups

80 Participants
are divided into 4 treatment groups
Group A: Group 1Experimental treatment 2 interventions
Group B: Group 2Sham comparator 2 interventions
Group C: Group 3Sham comparator 2 interventions
Group D: Group 4Placebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

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

The cognitive outcome is a balanced composite sum of z-scores of four executive function tests (Trails B, Digit-Symbol, and Category Fluency (animals, fruits and vegetables), four episodic memory tests (immediate and delayed recall of the word list from the ADAS-Cog, and immediate and delayed recall of Logical Memory Story I from the Wechsler Memory Test). Z-scores are reversed if necessary so that a positive value refers to good cognition. Cognitive functioning will be measured at baseline, 6 months, and 12 months follow-ups.

Time frame
12 months
2

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

Change in CBF will be measured using Arterial Spin Labeling (ASL) brain magnetic resonance imaging (MRI) scans. The unit of cerebral blood flow from ASL is ml/100g/min, which means the amount of blood flow into 100g of tissue in one minute. Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in blood flow between the time points.

Time frame
6 months
3

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

Brain Glucose intake will be measured by \[F18\]FDG-PET: Voxel-wise standardized uptake value ratio (SUVR) images will be created in native MRI space with the pons as reference region. \[F18\]FDG values will be extracted from ADRD-vulnerable regions of interest (dorsolateral prefrontal cortex, medial and lateral temporal lobe, and medial and lateral parietal cortex). Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in glucose intake between the time points.

Time frame
6 months

Secondary outcomes

1

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

Cognitive outcomes will be the domain-specific composites, for executive functions and episodic memory, by using four executive function tests (Trails B, Digit-Symbol, and Category Fluency \[animals, fruits and vegetables), and four episodic memory tests (immediate and delayed recall of the word list from the ADAS-Cog, and immediate and delayed recall of Logical Memory Story I from the Wechsler Memory Test). Cognitive outcomes will be measured at baseline, 6 months, and 12 months follow-ups

Time frame
12 months
2

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

Changes in White matter hyperintensity (WMH) volume: Total WMH volume of presumed ischemic origin will be quantified from 3D T2-FLAIR brain MRI using the Lesion Segmentation Tool. T1-weighted volumetric scans will be used to derive intracranial volume. Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in WMH volume between the time points.

Time frame
6 months
3

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

Changes in gray matter (GM) and hippocampal volumes: neurodegeneration will be measured using T1-weighted scans brain MRI scans. Regional cortical GM and hippocampal volumes will be extracted using FreeSurfer 7.1.1. and FSL. Scans will be taken at baseline and 6 months follow-up. Baseline and 6 months scans will be compared and analyzed to assess change in GM and hippocampal volumes between the time points.

Time frame
6 months
4

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

Change in functional performance will be measured by the Clinical Dementia Rating (CDR) Scale Sum of Boxes (SB). The CDR-SB summarizes cognitive impairment in 6 domains (memory, orientation, judgment/problem-solving, community affairs, home/hobbies, and personal care) based on subject and informant interviews. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). A maximal CDR-SB score is -18. CDR will be measured at baseline, 6 months, and 12 months follow-ups.

Time frame
12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Rutgers, The State University of New Jersey

Lead sponsor

Alzheimer's Association

Collaborator

Source ClinicalTrials.gov
Apply now