Overview

This trial is active, not recruiting.

Conditions post bariatricsurgery, hypoglycemia
Treatments exendin-(9-39), atropine, glp-1 and gip
Phase phase 0
Sponsor Cedars-Sinai Medical Center
Start date October 2009
End date July 2020
Trial size 160 participants
Trial identifier NCT00992901, DK083554

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model crossover assignment
Masking open label
Arm
(Experimental)
To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
exendin-(9-39) No other name for Exendin-(9-39)
A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
(Experimental)
To evaluate the effect of neural activation on insulin secretion and glucose metabolism
atropine Atropine sulfate
A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism
(Experimental)
to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
glp-1 and gip No other names for GLP-1 and GIP.
A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones

Primary Outcomes

Measure
Gut hormones and neural signaling contribution to insulin secretion rate and glucose tolerance
time frame: Each study of the protocol is conducted up to seven hours with data collected at intervals specific to the individual study procedure.

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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 Children's Hospital Medical Center in Cincinnati 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

Additional Information

Official title Hormonal and Neural Control of Insulin Secretion Following Gastric Bypass Surgery
Principal investigator Marzieh Salehi, MD, MS
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
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Cedars-Sinai Medical Center.