Modeling the Neurological Basis and Characterizing the Neurological Phenotype of Obesity Using Human Neural Stem Cells

Study Overview
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Brief Summary
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This study aims to characterize the neurological basis of obesity and response to surgical and medical treatment by inducing adult pluripotent stem cells into neuronal cells from subjects that have demonstrated extreme response to bariatric surgery or pharmacological treatment for obesity.

Detailed Description
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The investigators will consent subjects who have achieved extreme response to either bariatric surgery or pharmacologic treatment for obesity and harvest fibroblasts from skin biopsies, which will be reprogrammed to induced pluripotent stem cells (iPSC). These iPSC's will then be differentiated into neural progenitor cells, neurons, astrocytes, and microglia to identify genetic and epigenetic pathways altered in disease-specific neural progenitor cells of the brain.

Official Title
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Modeling the Neurological Basis and Characterizing the Neurological Phenotype of Obesity Using Human Neural Stem Cells

Conditions
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Obesity, Morbid

Intervention / Treatment
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* Procedure: Bariatric Surgery
* Drug: Anti Obesity Drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of obesity Treatment with bariatric surgery Treatment with anti obesity medications Greater than 70% excess weight loss at least 6 months after surgery Greater than 15% weight loss on anti obesity medications Exclusion Criteria: Active cancer, not including non-melanoma skin cancer Active eating disorder Use of anti obesity medications in subjects with a history of bariatric surgery Active complication of the upper GI tract in patients with a history of bariatric surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bariatric Surgery<br>Subjects that have demonstrated extreme response to bariatric surgery. | Procedure: Bariatric Surgery<br>* Sleeve gastrectomy or Roux-en-Y Gastric Bypass<br>|
| Anti Obesity Medications<br>Subjects that have demonstrated extreme response to anti obesity pharmacotherapy. | Drug: Anti Obesity Drugs<br>* Response to FDA approved anti obesity medications<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA sequencing | Perform DNA sequencing from skin biopsy progenitor cells | 4 months | 
| Generate human cell based models of obesity | Fibroblasts will be expanded in culture and then reprogrammed to hiPSCs. | 4 months | 
| Differentiation to human CNS cells | Disease specific hiPSCs cells will be differentiated into neural progenitor cells, neurons, astrocytes, and microglia | 4 months | 
| Identification of genetic and epigenetic pathways | Identify genetic and epigenetic pathways altered in disease-specific neural progenitor cells, neurons, and non-neuronal cells of the brain | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti Obesity Medications, Weight Regulation, Pluripotent Stem Cells, Obesity, Bariatric Surgery