Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
80 participants
INTERVENTIONAL
2024-01-30
2028-12-01
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
QUADRUPLE
Study Groups
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Group 1
Will receive intranasal insulin therapy as well as Oral Semaglutide.
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.
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.
Group 2
Will receive active intranasal insulin therapy and placebo Oral Semaglutide.
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.
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.
Group 3
Will receive intranasal insulin placebo and active Oral Semaglutide .
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.
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.
Group 4
Will receive intranasal insulin placebo and Oral Semaglutide placebo.
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.
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.
Interventions
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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.
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.
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.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
60 Years
90 Years
ALL
No
Sponsors
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Alzheimer's Association
OTHER
Rutgers, The State University of New Jersey
OTHER
Responsible Party
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Michal Schnaider Beeri, Ph.D.
Director, Alzheimer's Research Center.
Principal Investigators
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Tal Davidy
Role: STUDY_DIRECTOR
Sheba Medical Center
Michal Schnaider beeri
Role: PRINCIPAL_INVESTIGATOR
Rutgers, The State University of New Jersey
Locations
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Joseph Sagol Neuroscience center, Sheba Medical Center
Ramat Gan, , Israel
Countries
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Central Contacts
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Facility Contacts
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References
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
Pro2023001136
Identifier Type: -
Identifier Source: org_study_id
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