Pre-operative Intranasal Oxytocin for Enhancing Bariatric-induced Diabetes Remission

Study Overview
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Brief Summary
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This is a randomized, double blind, placebo-controlled study of the effects of intranasal oxytocin in obese adults with diabetes undergoing bariatric surgery. Subjects will be randomized to receive of intranasal oxytocin or placebo (8 units 3 times daily) for 8 weeks prior surgery. Study visits include screening to determine eligibility, CGM will be connected before and after oxytocin administration, and 1 year post surgery. blood tests including oral glucose tolerance test will be done and fat samples will be taken during surgery. The investigator's hypothesis is that oxytocin administration prior bariatric surgery can induce diabetes remission in patients with diabetes

Official Title
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Pre-operative Intranasal Oxytocin for Enhancing Bariatric-induced Diabetes remissionPre-operative Intranasal Oxytocin for Enhancing Bariatric-induced Diabetes Remission

Conditions
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Obesity, Diabetes, Bariatric Surgery

Intervention / Treatment
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* Drug: Oxytocin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 Diabetes Mellitus type 2 HBA1C < or= 9 BMI >35 eligible for bariatric surgery (after a hospital bariatric committee) Advanced diarem>6 Signed an informed consent - Exclusion Criteria: HBA1C above 9 Prior bariatric surgery in the past 6 years secondary diabetes steroid therapy uncontrolled hypertension(>180/100) Arythmia: paroxysmal tachyarythmia or high degree AV-Block

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oxytocin<br>8 U/oxytocin three-times daily, 30 min before breakfast, lunch and dinner, using a nasal atomizer for 8 weeks | Drug: Oxytocin<br>* 8 weeks intranasal oxytocin 24 units per day. 8 units prior each meal. 4units/0.1 ml per puff<br>|
| Placebo Comparator: placebo<br>intranasal spray containing placebo three-times daily, 30 min before breakfast, lunch and dinner, using a nasal atomizer for 8 weeks | Drug: placebo<br>* 8 weeks intranasal placebo 0.6 ml per day. . 0.1 ml per puff<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with diabetes remission 1 year post surgery | HBA1C less then 6.5% without need for diabetes medication | 1 year post surgery | 
| Number of participants who improved their glycemic control | increase in Time in Range by 10% and or decrease in HBA1C by 1 % 8 weeks from treatment | 8 weeks | 
| weight loss | weight reduction - kg. | 8 weeks | 
| weight loss | weight reduction - kg. | 1 year | 
| obesity | change in waist circumference | 8 weeks | 
| obesity | change in waist circumference | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Insulin secretion | Increase of insulin secretion after oxytocin administration | 8 weeks | 
| Rate of Insulin secretion | Increase of insulin secretion after oxytocin administration | 1 year | 
| Rate of insulin resistance | Increase of insulin sensitivity after oxytocin administration | 8 weeks | 
| Rate of insulin resistance | Increase of insulin sensitivity after oxytocin administration | 1 year | 
| lipids-LDL CHOLESTEROL | change in lipid profile: LDL | 8 weeks | 
| lipids-LDL CHOLESTEROL | change in lipid profile: LDL | 1 year | 
| lipids-HDL CHOLESTEROL | change in lipid profile: HDL | 8 weeks | 
| lipids-HDL CHOLESTEROL | change in lipid profile: HDL | 1 year | 
| lipids-NON HDL CHOLESTEROL | change in lipid profile: NON HDL cholesterol. triglycerides | 8 weeks | 
| lipids-NON HDL CHOLESTEROL | change in lipid profile: NON HDL cholesterol. triglycerides | 1 year | 
| lipids-Triglycerides | change in lipid profile: triglycerides | 8 weeks | 
| lipids-Triglycerides | change in lipid profile: triglycerides | 1 year | 
| blood pressure | change in systolic and diastolic blood pressure | 8 weeks | 
| blood pressure | change in systolic and diastolic blood pressure | 1 year | 
| urine microalbumin | Change in microalbumin/creatinin | 8 weeks | 
| urine microalbumin | Change in microalbumin/creatinin | 1 year | 
| HPA axis | change in cortisol | 8 weeks | 
| HPA axis | change in cortisol | 1 year | 
| HPA axis | change in ACTH | 8 weeks | 
| HPA axis | change in ACTH | 1 year | 
| systemic inflammation | changes of inflammation markers: hrCRP | 8 weeks | 
| systemic inflammation | changes of inflammation markers: hrCRP | 1 year | 
| systemic inflammation | changes of inflammation markers: IL-6 | 8 weeks | 
| systemic inflammation | changes of inflammation markers: IL-6 | 1 year | 
| systemic inflammation | changes of inflammation markers: TNFα | 8 weeks | 
| systemic inflammation | changes of inflammation markers: TNFα | 1 year | 
| systemic inflammation | changes of inflammation markers: IL-1α | 8 weeks | 
| systemic inflammation | changes of inflammation markers: IL-1α | 1 year | 
| systemic inflammation | changes of inflammation markers: IL-1RA | 8 weeks | 
| systemic inflammation | changes of inflammation markers: IL-1RA | 1 year | 
| systemic inflammation | changes of inflammation markers: IL-17 | 8 weeks | 
| systemic inflammation | changes of inflammation markers: IL-17 | 1 year | 
| systemic inflammation | changes of inflammation markers: IL-21 | 8 weeks | 
| systemic inflammation | changes of inflammation markers: IL-21 | 1 year | 
| systemic inflammation | changes of inflammation markers: adiponectin | 8 weeks | 
| systemic inflammation | changes of inflammation markers: adiponectin | 1 year | 
| systemic inflammation | changes of inflammation markers: leptin | 8 weeks | 
| systemic inflammation | changes of inflammation markers:leptin | 1 year | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: E2F1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: ASK1/2 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: LC3-II | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: family of ATGs | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:p-62 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: TRAL | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: TL-1A | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CCL5 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:RB1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:LEPTIN. | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CCL2, | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:CCL8 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:CD68 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: BECN1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: TFDP1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: ADIPOQ, | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: NCK2 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: TP53 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: COL6A1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: COL3A1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: KIT | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CMA1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: RIPK1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:TNF | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CD36 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: IL-6 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: ELN | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CD11C | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:CD206 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CD163 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CD209 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: CTGF | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: PEPD | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: PAI-1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: BCKDHB | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated:HADHA | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: MMUT | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: ALDH6A1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: endogenous control-PGK1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Real time PCR - mRNA will be extracted, cDNA will be generated and the following genes will be evaluated: endogenous control PPIA | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: E2F1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: ASK1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: p-62 | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: TRAL | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: TL-1A, | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: PEPD | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: PAI-1 | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: family of ATGs | 8 weeks | 
| omental and subcutaneous fat inflammation | Western blot analysis -The following proteins will be evaluated: endogenous control -beta-actin | 8 weeks | 
| omental and subcutaneous fat inflammation | ELISA: adiponectin | 8 weeks | 
| omental and subcutaneous fat inflammation | ELISA: leptin | 8 weeks | 
| omental and subcutaneous fat inflammation | ELISA: TNF | 8 weeks | 
| omental and subcutaneous fat inflammation | ELISA: IL-6 | 8 weeks | 
| omental and subcutaneous fat inflammation | histological studies :Adipocyte size distribution. | 8 weeks | 
| omental and subcutaneous fat inflammation | histological studies : CD68 staining | 8 weeks | 
| omental and subcutaneous fat inflammation | histological studies :,c-kit staining | 8 weeks | 
| omental and subcutaneous fat inflammation | Culture of explants in media for up to 1 week for obtaining medium with secreted products of the tissue. Following secreted products will be measured using ELISA: adiponectin | 8 weeks | 
| omental and subcutaneous fat inflammation | Culture of explants in media for up to 1 week for obtaining medium with secreted products of the tissue. Following secreted products will be measured using ELISA: leptin | 8 weeks | 
| omental and subcutaneous fat inflammation | Culture of explants in media for up to 1 week for obtaining medium with secreted products of the tissue. Following secreted products will be measured using ELISA: TNF | 8 weeks | 
| omental and subcutaneous fat inflammation | Culture of explants in media for up to 1 week for obtaining medium with secreted products of the tissue. Following secreted products will be measured using ELISA: IL-6 | 8 weeks | 
| omental and subcutaneous fat inflammation | Culture of explants in media for up to 1 week for obtaining medium with secreted products of the tissue. Following secreted products will be measured using ELISA: CTRP6/12/2 (ng/ml). | 8 weeks |