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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Cedars-Sinai Medical Center
Sponsor:
Information provided by (Responsible Party):
Marzieh Salehi, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT00992901
First received: October 7, 2009
Last updated: August 31, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Post Bariatricsurgery
Hypoglycemia
Drug: Exendin-(9-39)
Drug: Atropine
Drug: GLP-1 and GIP
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Hormonal and Neural Control of Insulin Secretion Following Gastric Bypass Surgery

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: October 2009
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exendin-(9-39)
To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
Drug: Exendin-(9-39)
A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
Other Name: No other name for Exendin-(9-39)
Experimental: atropine
To evaluate the effect of neural activation on insulin secretion and glucose metabolism
Drug: Atropine
A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism
Other Name: Atropine sulfate
Experimental: GLP-1 and GIP
to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
Drug: GLP-1 and GIP
A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
Other Name: No other names for GLP-1 and GIP.

Detailed 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
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992901

Contacts
Contact: Rashin Sedighi, PhD, MS 310-423-3533 Rashin.Sedighi@cshs.org
Contact: Marzieh Salehi, MD, MS 310-967-2779 marzieh.salehi@cshs.org

Locations
United States, California
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Rashin Sedighi, PhD,MS    310-423-3533    Rashin.Sedighi@cshs.org   
Contact: Marzieh Salehi, MD,MS    310-967-2779    marzieh.salehi@cshs.org   
Principal Investigator: Marzieh Salehi, MD, MS         
Sponsors and Collaborators
Cedars-Sinai Medical Center
Investigators
Principal Investigator: Marzieh Salehi, MD, MS Cedars-Sinai Medical Center
  More Information

Responsible Party: Marzieh Salehi, Associate Professor, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT00992901     History of Changes
Other Study ID Numbers: DK083554  DK083554 
Study First Received: October 7, 2009
Last Updated: August 31, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Cedars-Sinai Medical Center:
gastric bypass surgery
glucose tolerance
Insulin response to meal ingestion
Gut hormone and neural response to meal ingestion

Additional relevant MeSH terms:
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Insulin, Globin Zinc
Insulin
Hormones
Glucagon-Like Peptide 1
Glucagon
Atropine
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Adjuvants, Anesthesia
Anti-Arrhythmia Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Parasympatholytics
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Incretins
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 30, 2016