Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery

NCT00992901 | Recruiting Early Phase 1 DMC

• 2 other identifiers: 18-070HDK083554
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 2

Brief Summary

RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls.

Conditions

Post Bariatricsurgery; Hypoglycemia

Keywords

gastric bypass surgery; glucose tolerance; Insulin response to meal ingestion; Gut hormone and neural response to meal ingestion

Outcome Measures

Primary Outcomes (1)

• Gut hormones and neural signaling contribution to insulin secretion rate and glucose tolerance

  Each study of the protocol is conducted up to seven hours with data collected at intervals specific to the individual study procedure.

Study Arms (3)

Exendin-(9-39)

EXPERIMENTAL

To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion

Drug: Exendin-(9-39)

atropine

EXPERIMENTAL

To evaluate the effect of neural activation on insulin secretion and glucose metabolism

Drug: Atropine

GLP-1 and GIP

EXPERIMENTAL

to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Drug: GLP-1 and GIP

Interventions

Exendin-(9-39) DRUG

A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion

Also known as: No other name for Exendin-(9-39)

Exendin-(9-39)

Atropine DRUG

A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism

Also known as: Atropine sulfate

atropine

GLP-1 and GIP DRUG

A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Also known as: No other names for GLP-1 and GIP.

GLP-1 and GIP

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hypoglycemic RYGB patients with documented blood glucose level \<50 mg/dl
• Asymptomatic individuals with bariatric surgery
• Healthy non-surgical patients with no personal history of diabetes
• Subjects must physically be able to come to our clinical research center at Cedars-Sinai Medical Center

You may not qualify if:

• Active heart, lung, liver, gastrointestinal or kidney disease; unable to give informed consent; pregnancy; uncontrolled high blood pressure or high cholesterol; significant anemia (hemoglobin \<11g/dL); prisoners or institutionalized individuals; type 2 diabetes melitis; development of any serious medical or psychiatric illness during recruitment or studies;
• RYGB patients will also be disqualified if they have gastric outlet obstruction or severe diarrhea
• Healthy non-surgical patients with personal history of diabetes
• History of glaucoma
• Uncontrolled hypertension (any subjects with BP\>140/90 and history of dyslipidemia
• Taking any medication that might interact with atropine and cannot be stopped will be excluded from the study)
• Myasthenia gravis
• Brain pathology
• Enlarged prostate in men

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (2)

Texas Diabetes Institute - University Health System

San Antonio, Texas, 78207, United States

RECRUITING

South Texas Veterans Health Care System

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Hypoglycemia

Interventions

exendin (9-39); Atropine; Glucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Marzieh Salehi, MD, MS

  Marzieh Salehi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marzieh Salehi, MD MS

CONTACT

210-567-6691; salehi@uthscsa.edu

Jennifer Foster, MSN

CONTACT

210-450-8696; fosterj6@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2009
• First Posted: October 9, 2009
• Study Start: October 1, 2009
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)