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

Hypoglycemia Clinical Trial

Official title:

Hormonal and Neural Control of Insulin Secretion Following Gastric Bypass Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00992901
• Other study ID #: 18-070H
• Secondary ID: DK083554
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 2009
• Est. completion date: August 2026

Study information

• Verified date: August 2023
• Source: The University of Texas Health Science Center at San Antonio
• Contact: Marzieh Salehi, MD MS
• Phone: 210-567-6691
• Email: salehi[@]uthscsa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: August 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

For administration of atropine, the following exclusions also apply:

• 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

Related Conditions & MeSH terms

• Hypoglycemia
• Post Bariatricsurgery

Intervention

Drug:
• Exendin-(9-39)
A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
• Atropine
A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism
• GLP-1 and GIP
A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Locations

Country	Name	City	State
United States	South Texas Veterans Health Care System	San Antonio	Texas
United States	Texas Diabetes Institute - University Health System	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.