Human Intestinal Peptides Evaluation and Research

Obesity Clinical Trial

— HIPER  

Official title:

Effects of Different Metabolic States and Surgical Models on Glucose Metabolism and Secretion of Ileal L-cell Peptides

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02532829
• Other study ID #: 2015/H01
• Status: Enrolling by invitation
• Phase: N/A
• First received: August 13, 2015
• Last updated: October 24, 2016
• Start date: September 2015
• Est. completion date: November 2016

Study information

• Verified date: July 2016
• Source: Turkish Metabolic Surgery Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Turkey: Ethics Committee
• Study type: Observational

Clinical Trial Summary

The HIPER-1 study is a single centre cross sectional study in which a total of 240 participants (in different metabolic states and surgical models) will receive an Oral Mixed Meal Tolerance Test (OMTT). At baseline and after 30, 60 and 120 minutes the PYY levels, GLP-1 levels, glucose and insulin sensitivity will be measured. The primary endpoint of the study will be the area under the GLP-1 and Peptide - YY curves and insulin sensitivity following the OMTT.

Description:

Obesity and type 2 diabetes mellitus (T2DM) are increasing worldwide, thus reaching pandemic proportions. Diet, exercise and medication remain the cornerstones of type 2 diabetes mellitus treatment. But, apart from studies demonstrating promising results in some of the developed countries; the long-term success rates of lifestyle and drug modifications are disappointing. In cases where classic strategies proved to be inadequate, broad type of gastrointestinal (GI) surgery methods offer new alternatives to treat obesity and T2DM. The variable levels of incretin stimulation (especially GLP-1) and improved glycaemic control in those with diabetes have been shown following various bariatric techniques.

Therefore, investigators aimed to analyze the levels of GLP-1 and Peptide YY hormones together with indices of insulin sensitivity in participants with various health conditions and in participants who underwent different surgical options including sleeve gastrectomy, minigastric bypass, sleeve gastrectomy with ileal transposition and sleeve gastrectomy with transit bipartition.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 240
• Est. completion date: November 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 60 Years

Eligibility

For NON-SURGERY GROUPS

Inclusion Criteria:

1. GROUP NS-A: Healthy participants, no known disease, no previous surgery, HbA1c<5.7%, BMI<25 kg/m2 (n=30).

GROUP NS-B: Obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI>30 kg/m2 (n=30).

GROUP NS-C: Non-obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI<30 kg/m2 (n=30).

GROUP NS-D: Obese non-diabetics, HbA1c<5.7%, No signs and history of T2D, and BMI>30 kg/m2 (n=30).

2. Preferably not on any kind of anti-diabetic drugs or will accept cessation of all anti-diabetic drugs 2 days prior to evaluation.

3. Absence of co-morbidities (dyslipidemia, hypertension, neuropathy, retinopathy, cardiovascular disease, stroke events or lower extremity amputation).

4. Possibility to participate to the quadruplicate measurement protocol.

Exclusion Criteria:

1. Anti insulin / islet antibody and glutamic acid decarboxylase antibody (antiGAD) positivity, plasma fasting C-peptide lesser than 1 ng/ml.

2. Liver cirrhosis, severe renal failure, collagen diseases, severe endocrinopathies, blindness.

3. Heart failure, acute myocardial infarction, stroke or transient ischemic attack, unstable angina pectoris.

4. History of malignancy or malignant neoplasm in place, severe inflammatory complications, neurological or cardiovascular in act.

5. Pregnancy

6. Any conditions that at the discretion of the head of the study can represent risk to the participant or could affect the protocol results.

For SURGERY GROUPS

Inclusion Criteria:

1. Type 2 Diabetic participants who underwent a sleeve gastrectomy, a mini-gastric bypass, a sleeve gastrectomy with ileal transposition or a sleeve gastrectomy with transit bipartition performed more than 6 months ago, but within the last 2 years, with steady weight profile.

2. Preferably not on any kind of anti-diabetic drugs or will accept cessation of all anti-diabetic drugs 2 days prior to evaluation.

3. Absence of or resolved co-morbidities (dyslipidemia, hypertension, neuropathy, retinopathy, cardiovascular disease, stroke events or lower extremity amputation).

4. Possibility to participate to the quadruplicate measurement protocol.

Exclusion Criteria:

1. Liver cirrhosis, severe renal failure, collagen diseases, severe endocrinopathies, blindness.

2. Heart failure, acute myocardial infarction, stroke or transient ischemic attack, unstable angina pectoris.

3. History of malignancy or malignant neoplasm in place, severe inflammatory complications, neurological or cardiovascular in act.

4. Pregnancy

5. Any conditions that at the discretion of the head of the study can represent risk to the participant or could affect the protocol results.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity

Intervention

Other:
• blood sample analysis
Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Turkish Metabolic Surgery Foundation

References & Publications (10)

Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 2003 Sep 4;349(10):941-8. — View Citation

Celik A, Ugale S. Functional restriction and a new balance between proximal and distal gut: the tools of the real metabolic surgery. Obes Surg. 2014 Oct;24(10):1742-3. doi: 10.1007/s11695-014-1368-x. — View Citation

DePaula AL, Macedo AL, Schraibman V, Mota BR, Vencio S. Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20-34. Surg Endosc. 2009 Aug;23(8):1724-32. doi: 10.1007/s00464-008-0168-6. — View Citation

Essah PA, Levy JR, Sistrun SN, Kelly SM, Nestler JE. Effect of weight loss by a low-fat diet and a low-carbohydrate diet on peptide YY levels. Int J Obes (Lond). 2010 Aug;34(8):1239-42. doi: 10.1038/ijo.2010.48. — View Citation

Finelli C, Padula MC, Martelli G, Tarantino G. Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion? World J Gastroenterol. 2014 Nov 28;20(44):16649-64. doi: 10.3748/wjg.v20.i44.16649. Review. — View Citation

Goldfine AB, Mun EC, Devine E, Bernier R, Baz-Hecht M, Jones DB, Schneider BE, Holst JJ, Patti ME. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Meta — View Citation

Kashyap SR, Bhatt DL, Wolski K, Watanabe RM, Abdul-Ghani M, Abood B, Pothier CE, Brethauer S, Nissen S, Gupta M, Kirwan JP, Schauer PR. Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized — View Citation

Kashyap SR, Daud S, Kelly KR, Gastaldelli A, Win H, Brethauer S, Kirwan JP, Schauer PR. Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes. I — View Citation

Santoro S. From Bariatric to Pure Metabolic Surgery: New Concepts on the Rise. Ann Surg. 2015 Aug;262(2):e79-80. doi: 10.1097/SLA.0000000000000590. — View Citation

Troke RC, Tan TM, Bloom SR. The future role of gut hormones in the treatment of obesity. Ther Adv Chronic Dis. 2014 Jan;5(1):4-14. doi: 10.1177/2040622313506730. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma HbA1c levels in participants with various health conditions.	Measurements will be performed in the fasting state using the Turbidometric Assay and results will be expressed as percentage (%).	Up to 6 months.	No
Other	Plasma HbA1c levels in participants treated by different bariatric and metabolic surgical techniques.	Measurements will be performed in the fasting state using the Turbidometric Assay and results will be expressed as percentage (%).	Up to 6 months.	No
Other	Plasma Liver Function Tests (SGOT, SGPT and GGT levels) in participants with various health conditions.	Measurements will be performed in the fasting state using IFCC Enzymatic Assay and results will be expressed as U/L.	Up to 6 months.	No
Other	Plasma Liver Function Tests (SGOT, SGPT and GGT levels) in participants treated by different bariatric and metabolic surgical techniques.	Measurements will be performed in the fasting state using IFCC Enzymatic Assay and results will be expressed as U/L.	Up to 6 months.	No
Primary	Plasma GLP-1 and P-YY measurements by ELISA in participants with various health conditions.	Measurements will be performed before and 30-60-120 minutes after a mixed meal test and results will be expressed as pmol/L.	Up to 6 months.	No
Primary	Plasma GLP-1 and P-YY measurements by ELISA in participants treated by different bariatric and metabolic surgical techniques.	Measurements will be performed before and 30-60-120 minutes after a mixed meal test and results will be expressed as pmol/L.	Up to 6 months.	No
Secondary	Body Mass Index (BMI) in participants with various health conditions.	BMI will be expressed in kg/m^2 (weight in kilograms and height in meters).	Up to 6 months.	No
Secondary	Body Mass Index (BMI) in participants treated by different bariatric and metabolic surgical techniques.	BMI will be expressed in kg/m^2 (weight in kilograms and height in meters).	Up to 6 months.	No
Secondary	Waist and hip circumference in participants with various health conditions.	Waist and hip circumferences will be expressed as centimeters.	Up to 6 months.	No
Secondary	Waist and hip circumference in participants treated by different bariatric and metabolic surgical techniques.	Waist and hip circumferences will be expressed as centimeters.	Up to 6 months.	No
Secondary	Plasma glucose levels in participants with various health conditions.	Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma glucose levels will be measured by Enzymatic Hexokinase method and results will be expressed as mg/dl.	Up to 6 months.	No
Secondary	Plasma glucose levels in participants treated by different bariatric and metabolic surgical techniques.	Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma glucose levels will be measured by Enzymatic Hexokinase method and results will be expressed as mg/dl.	Up to 6 months.	No
Secondary	Plasma insulin levels in participants with various health conditions.	Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma insulin levels will be measured by ECLIA method and results will be expressed as mU/ml.	Up to 6 months.	No
Secondary	Plasma insulin levels in participants treated by different bariatric and metabolic surgical techniques.	Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma insulin levels will be measured by ECLIA method and results will be expressed as mU/ml.	Up to 6 months.	No