Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Splanchnic Blood Redistribution After Incretin Hormone Infusion and Obesity Surgery (GIP-PET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01880827
Recruitment Status : Unknown
Verified May 2015 by Pirjo Nuutila, Turku University Hospital.
Recruitment status was:  Recruiting
First Posted : June 19, 2013
Last Update Posted : May 12, 2015
Sponsor:
Collaborators:
Lund University
Sigrid Jusélius Foundation
Academy of Finland
Information provided by (Responsible Party):
Pirjo Nuutila, Turku University Hospital

Brief Summary:

Obesity is a worldwide problem and leads to multiple metabolic and endocrinological problems.

Bariatric surgeries are a growing field as a treatment choice for morbid obesity (BMI > 35 kg/m2). Clinical and research evidence shows that shortly after RYGB, T2DM resolves with improving glucose tolerance. Foregut hypothesis behind bariatric surgeries postulate, that bypassed portions of intestine contain a substance, that acts as an anti-incretin, ie. to counteract metabolically favourable incretins. In view of the recent studies, it may be that GIP is really the anti-incretin behind this hypothesis.

The current study is conducted to investigate the vasoactive roles of the GIP. The investigators aim to show that GIP is the major contributor to the blood flow and tissue blood volume observed in postprandial state.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Obesity Procedure: Roux-en-Y Drug: GIP-infusion Drug: GLP-1 Drug: MMS Procedure: Sleeve gastrectomy Phase 1

Detailed Description:

Obesity is a worldwide problem and leads to multiple metabolic and endocrinological problems, including type 2 diabetes mellitus (T2DM). In T2DM, body is unable to response to circulating insulin levels, which ultimately destroys pancreatic β-cells, leading to chronic hyperglycaemia with ensuing consequences

Intestine is able to produce endocrinologically active substances, which affect to body's intermediary metabolism. One of these substances in glucose-dependent insulinotrophic polypeptide (GIP, part of the incretin family), which potentiates the release of insulin postprandially. However, recent evidence suggests, that GIP may have more harmful than beneficial role in the pathogenesis: it has been shown that GIP participates in the development of insulin resistance, the key defect in the process of metabolic dysfunction. GIP may also regulate postprandial redistribution of splanchnic blood flow which might act in the body's nutrition handling [8].

Bariatric surgeries are a growing field as a treatment choice for morbid obesity (BMI > 35 kg/m2). Most established of these procedures is a Roux-en-Y gastric bypass (RYGB), where duodenum and proximal jejunum is bypassed. Clinical and research evidence shows that shortly (before any significant weight loss) after RYGB, T2DM resolves with improving glucose tolerance. Foregut hypothesis behind bariatric surgeries postulate, that bypassed portions of intestine contain a substance, that acts as an anti-incretin¬, ie. to counteract metabolically favourable incretins. In view of the recent studies, it may be that GIP is really the anti-incretin behind this hypothesis.

Positron emission tomography (PET) is a modern imaging technique, which can be used to study perfusion and metabolism of different organs non-invasively. When radiowater measurement is combined with [15O]CO, both tissues specific perfusion and blood volume can be measured, respectively. When coupled with magnetic imaging (ie. PET-MRI), the volumes-of-interests can be accurately drawn to the desired organs.

The current study is conducted to investigate the vasoactive roles of the GIP. We aim to show that GIP is the major contributor to the blood flow and tissue blood volume observed in postprandial state. Moreover, we hypothesize that the elimination of GIP-effect has a central role in the improved intermediary metabolism observed after bariatric surgery procedures, and that part this change is mediated by changes in splanchnic circulation. Furthermore, we investigate the effect of GLP-1 (glucagon-like peptide 1, another member of incretin family) on splanchnic circulation.

In the present study intestinal, hepatic and pancreatic blood flow and volume are measured using [15O]H2O- and [15O]CO radiotracers and PET-MRI imaging in healthy normal weight volunteers (n = 20, BMI ≤ 27 kg/m2) and in morbidly obese T2DM patients (n = 30, BMI ≤ 35 kg/m2) before and after the bariatric surgery operation. The PET imaging will be performed at fasting state but also separately either during 1) mixed meal solution (MMS), 2) GIP-, or 3) GLP-1-infusion. Also abdominal subcutaneous and visceral adipose tissue, intestinal and hepatic tissue samples will be collected.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Effects of Glucose-dependent Insulinotrophic Peptide (GIP) and Glucagon-like Peptide 1 (GLP-1) on Splanchnic Redistribution of Blood Flow at Postprandial State and After Roux-en-Y Gastric Bypass and Sleeve
Study Start Date : January 2013
Estimated Primary Completion Date : November 2015
Estimated Study Completion Date : January 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Royx-en-Y surgery
Blood flow after surgery
Procedure: Roux-en-Y
Subjects in the intervention group will be divided into two consecutive surgical groups, and operated at the Department of Surgery at Turku University Hospital (Kiinamyllynkatu 4-8, Turku). During surgery, Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) is performed using standard laparoscopic techniques. In RYGB procedure large part of the ventricle, duodenum, and proximal jejunum (ad 1.5 meters from pylorus) is bypassed. "New" stomach pouch is anastomosed into the "new" proximal jejunum, and remaining larger portion of the stomach, duodenum, and jejunum are reattached to the distal part of the jejunum for the secretion of pancreatic, gastrointestinal, and biliary juice. In SG a notable amount of ventricle is removed to create a stomach pouch which effectively restricts the amount of food feasible to ingest. After the surgery, subjects are controlled in hospital ward for approximately three days.

Drug: GIP-infusion
Blood flow and volume during infusion

Drug: MMS
Blood flow and volume after meal solution

Active Comparator: Control
Healthy volunteer group, GIP, GLP-1 and MMS studies
Drug: GIP-infusion
Blood flow and volume during infusion

Drug: GLP-1
Blood flow and volume during infusion

Drug: MMS
Blood flow and volume after meal solution

Experimental: Sleeve gastrectomy
Blood flow after surgery
Drug: GIP-infusion
Blood flow and volume during infusion

Drug: MMS
Blood flow and volume after meal solution

Procedure: Sleeve gastrectomy



Primary Outcome Measures :
  1. Splanchnic blood flow [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. GIP and GLP-1 blood concetrations [ Time Frame: 24 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. BMI > 35 kg/m2
  2. Type 2 diabetes mellitus (fasting glucose more than 7 mmol/l)
  3. Age: 18-60 years
  4. Previous, carefully planned, conservative treatments for obesity have failed

Exclusion Criteria:

  1. BMI over 60 kg/m2
  2. Weight more than 170 kg
  3. Waist circumference > 150 cm
  4. Insulin treatment requiring type 2 diabetes mellitus
  5. Mental disorder or poor compliance
  6. Eating disorder or excessive use of alcohol
  7. Active ulcus-disease
  8. Pregnancy
  9. Past dose of radiation
  10. Presence of any ferromagnetic objects that would make MR imaging contraindicated
  11. Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results

Inclusion criteria for the control group

  1. BMI 18-27 kg/m2
  2. Age 18-60 years
  3. Fasting plasma glucose less than 6.1 mmol/l
  4. Normal glucose tolerance test (OGTT)

Exclusion criteria for the control group

  1. Blood pressure > 140/90 mmHg
  2. Any chronic disease
  3. Mental disorder or poor compliance
  4. Any chronic medical defect or injury which hinder/interfere everyday life
  5. Eating disorder or excessive use of alcohol
  6. Pregnancy
  7. Past dose of radiation
  8. Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
  9. Presence of any ferromagnetic objects that would make MR imaging contraindicated
  10. Smoking

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01880827


Contacts
Layout table for location contacts
Contact: Pirjo Nuutila, Prof +35823130000 pirnuu@utu.fi
Contact: Jukka P Koffert, MD, PhD student +31323130000 jpmatt@utu.fi

Locations
Layout table for location information
Finland
Turku univercity hospital, PET center Recruiting
Turku, Finland, 20540
Contact: Jukka P Koffert, MD, PhD student    +35823130000    jukka.koffert@tyks.fi   
Sub-Investigator: Jukka P Koffert, MD,PhDstudent         
Sponsors and Collaborators
Turku University Hospital
Lund University
Sigrid Jusélius Foundation
Academy of Finland
Investigators
Layout table for investigator information
Principal Investigator: Pirjo Nuutila, Prof PET centre, Turku

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pirjo Nuutila, Professor, Turku University Hospital
ClinicalTrials.gov Identifier: NCT01880827     History of Changes
Other Study ID Numbers: 2012-002689-10
First Posted: June 19, 2013    Key Record Dates
Last Update Posted: May 12, 2015
Last Verified: May 2015
Keywords provided by Pirjo Nuutila, Turku University Hospital:
GIP
GLP-1
type 2 diabetes
obesity
splanchnic blood flow
incretin hormones
Additional relevant MeSH terms:
Layout table for MeSH terms
Obesity
Diabetes Mellitus, Type 2
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glucagon
Gastric Inhibitory Polypeptide
Glucagon-Like Peptide 1
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Gastrointestinal Agents