Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ghrelin and Beta Cell Function in Diabetes

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: NCT02440061
Recruitment Status : Withdrawn (This protocol was replaced with a different one and therefore discontinued.)
First Posted : May 12, 2015
Last Update Posted : April 2, 2018
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Jenny Tong, MD, MPH, Duke University

Brief Summary:
Ghrelin is a hormone naturally produced in the stomach and the gut. The purpose of this research study is to determine the role of this gut hormone in the regulation of insulin secretion from the pancreas and glucose disposal after we eat. The investigators hypothesize that ghrelin has an effect on the pancreas and on how our body handles glucose after we eat. The investigators will compare insulin secretion and glucose changes during meal ingestion while either acyl ghrelin (AG) or saline (salt solution) is being infused through your vein on separate study days. AG is a form of the ghrelin hormone that has a small modification to it that allows it to bind to a specific receptor. The investigators hypothesize that AG has an effect on how the body handles glucose after a meal. AG has been approved by the U.S. Food and Drug Administration (FDA) for human research only. This study will also involve the use of a medicine called arginine, which is a naturally occurring product and found in many nutritional supplements. Its use in this study is investigational. The use of arginine helps maximize insulin release from the pancreas so the investigators can better examine whether AG affects insulin secretion.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Synthetic human AG Drug: Arginine Drug: 0.9% saline solution Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Ghrelin Effect on Beta Cell Function in Health and Disease #2
Estimated Study Start Date : May 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Study Group: Type 2 Diabetes Mellitus (T2DM)
Subjects with Type 2 Diabetes Mellitus (T2DM). Subjects will receive AG and saline infusions, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
Drug: Synthetic human AG
Synthetic human AG (0.28 μg/kg) bolus over 1 minute followed by 2 μg/kg/hr continuous infusion for 4.5 hours.

Drug: Arginine
Arginine hydrochloride (5 g) intravenously over 45 seconds.

Drug: 0.9% saline solution
A continuous infusion of 0.9% saline solution (control) for 4.5 hours.

Active Comparator: Control Group
Control group of healthy subjects. Subjects will receive AG and saline, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.
Drug: Synthetic human AG
Synthetic human AG (0.28 μg/kg) bolus over 1 minute followed by 2 μg/kg/hr continuous infusion for 4.5 hours.

Drug: Arginine
Arginine hydrochloride (5 g) intravenously over 45 seconds.

Drug: 0.9% saline solution
A continuous infusion of 0.9% saline solution (control) for 4.5 hours.




Primary Outcome Measures :
  1. Postprandial insulin secretion (ISR-meal) [ Time Frame: approximately 8 weeks ]
    Postprandial insulin secretion (ISR-meal) will be derived from plasma C-peptide concentrations during MTT (0-240 min) using deconvolution with population estimates of C-peptide clearance.

  2. Index of β-cell sensitivity to glucose [ Time Frame: approximately 8 weeks ]
    Index of β-cell sensitivity to glucose will be calculated as incremental insulin/glucose (I/G) AUC (ΔAUCI/G).

  3. Whole body insulin sensitivity using the Matsuda Index [ Time Frame: approximately 8 weeks ]
    The Matsuda Index is a well-known index of insulin sensitivity derived from several glucose and insulin values obtained during a mixed meal

  4. β-cell function (DI-meal) [ Time Frame: approximately 8 weeks ]
    β-cell function (DI-meal) will be calculated as ΔAUCI/G x Matsuda Index



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 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

T2DM study subjects to be considered for the study must meet the following inclusion criteria:

  1. Established T2DM with good to moderate glycemic control
  2. HbA1c < 8.5%
  3. Diabetes treatment with metformin, sulfonylurea, thiazolidinediones or combination of these medications; with no use of insulin during the study period
  4. BMI ≤ 45.0 kg/m2

Control study subjects will be matched for age- (± 2 years), BMI (± 1.5 kg/m2) and gender and must meet the following inclusion criteria:

  1. HbA1c ≤ 5.7%
  2. Fasting plasma glucose ≤ 95 mg/dL
  3. BMI ≤ 45.0 kg/m2

Exclusion Criteria:

All subjects will be excluded for the following reasons:

  1. History of myocardial infarction or arrhythmia within the past year, abnormal electrocardiogram (ECG) with evidence of ischemia or arrhythmia, history or symptoms of congestive heart failure
  2. Uncontrolled hypertension
  3. History or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [eGFR] <60 at screening)
  4. History of pituitary or adrenal disorders or neuroendocrine tumor
  5. Anemia defined as hematocrit <33% at screening
  6. Active cancer diagnosis or currently undergoing cancer treatment
  7. History of anorexia nervosa or previous gastrointestinal tract surgery
  8. Pregnancy or lactation

Control subjects will be excluded for the following reasons:

  1. History or clinical evidence of impaired fasting glucose or impaired glucose tolerance on a 75 g OGTT, established diabetes mellitus, or taking medications prescribed for diabetes
  2. Use of medications that alter insulin sensitivity (i.e. niacin, glucocorticoids, metformin)

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): NCT02440061


Locations
Layout table for location information
United States, North Carolina
Duke Center For Living
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Jenny Tong, MD, MPH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: Jenny Tong, MD Duke University

Layout table for additonal information
Responsible Party: Jenny Tong, MD, MPH, Associate Professor, Duke University
ClinicalTrials.gov Identifier: NCT02440061     History of Changes
Other Study ID Numbers: Pro00060865
R01DK097550 ( U.S. NIH Grant/Contract )
First Posted: May 12, 2015    Key Record Dates
Last Update Posted: April 2, 2018
Last Verified: March 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jenny Tong, MD, MPH, Duke University:
Ghrelin
age, BMI, and gender matched controls
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases