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

Overview

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.

Study Type

• Study Type: Observational
• Study Design
  • Time Perspective: Retrospective
• Study Primary Completion Date: August 10, 2020

Detailed Description

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.

Interventions

• Procedure: Bariatric Surgery
  • Sleeve gastrectomy or Roux-en-Y Gastric Bypass
• Drug: Anti Obesity Drugs
  • Response to FDA approved anti obesity medications

Arms, Groups and Cohorts

• Bariatric Surgery
  • Subjects that have demonstrated extreme response to bariatric surgery.
• Anti Obesity Medications
  • Subjects that have demonstrated extreme response to anti obesity pharmacotherapy.

Clinical Trial Outcome Measures

Primary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University of California, San Diego
• Provider of Information About this Clinical Study
  • Principal Investigator: Eduardo Grunvald, Clinical Professor of Medicine – University of California, San Diego
• Overall Official(s)
  • Eduardo Grunvald, MD, Principal Investigator, UCSD