Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery
Primary Purpose
Post Bariatricsurgery, Hypoglycemia
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Exendin-(9-39)
Atropine
GLP-1 and GIP
Sponsored by
About this trial
This is an interventional other trial for Post Bariatricsurgery focused on measuring gastric bypass surgery, glucose tolerance, Insulin response to meal ingestion, Gut hormone and neural response to meal ingestion
Eligibility 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
Sites / Locations
- Texas Diabetes Institute - University Health SystemRecruiting
- South Texas Veterans Health Care SystemRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Exendin-(9-39)
atropine
GLP-1 and GIP
Arm Description
To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
To evaluate the effect of neural activation on insulin secretion and glucose metabolism
to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
Outcomes
Primary Outcome Measures
Gut hormones and neural signaling contribution to insulin secretion rate and glucose tolerance
Secondary Outcome Measures
Full Information
NCT ID
NCT00992901
First Posted
October 7, 2009
Last Updated
August 21, 2023
Sponsor
The University of Texas Health Science Center at San Antonio
1. Study Identification
Unique Protocol Identification Number
NCT00992901
Brief Title
Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery
Official Title
Hormonal and Neural Control of Insulin Secretion Following Gastric Bypass Surgery
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2009 (undefined)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Bariatricsurgery, Hypoglycemia
Keywords
gastric bypass surgery, glucose tolerance, Insulin response to meal ingestion, Gut hormone and neural response to meal ingestion
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Exendin-(9-39)
Arm Type
Experimental
Arm Description
To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
Arm Title
atropine
Arm Type
Experimental
Arm Description
To evaluate the effect of neural activation on insulin secretion and glucose metabolism
Arm Title
GLP-1 and GIP
Arm Type
Experimental
Arm Description
to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
Intervention Type
Drug
Intervention Name(s)
Exendin-(9-39)
Other Intervention Name(s)
No other name for Exendin-(9-39)
Intervention Description
A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
Intervention Type
Drug
Intervention Name(s)
Atropine
Other Intervention Name(s)
Atropine sulfate
Intervention Description
A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism
Intervention Type
Drug
Intervention Name(s)
GLP-1 and GIP
Other Intervention Name(s)
No other names for GLP-1 and GIP.
Intervention Description
A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
Primary Outcome Measure Information:
Title
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marzieh Salehi, MD MS
Phone
210-567-6691
Email
salehi@uthscsa.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Hansis-Diarte
Phone
210-567-6691
Email
hansisdiarte@uthscsa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marzieh Salehi, MD, MS
Organizational Affiliation
Marzieh Salehi
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas Diabetes Institute - University Health System
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78207
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Hansis-Diarte, MPh
Phone
210-567-6691
Email
hansisdiarte@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Marzieh Salehi, MD, MS
Phone
210-567-6691
Email
salehi@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Marzieh Salehi
Facility Name
South Texas Veterans Health Care System
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marzieh Salehi
Phone
210-567-6691
Email
salehi@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Andrea Hansis-Diarte
Phone
210-567-6691
Email
hansisdiarte@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Marzieh Salehi, MD, MS
12. IPD Sharing Statement
Plan to Share IPD
No
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Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery
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