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Ghrelin and Beta Cell Function in Diabetes

Primary Purpose

Type 2 Diabetes Mellitus

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Synthetic human AG

Arginine

0.9% saline solution

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Ghrelin, age, BMI, and gender matched controls

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Established T2DM with good to moderate glycemic control
HbA1c < 8.5%
Diabetes treatment with metformin, sulfonylurea, thiazolidinediones or combination of these medications; with no use of insulin during the study period
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:

HbA1c ≤ 5.7%
Fasting plasma glucose ≤ 95 mg/dL
BMI ≤ 45.0 kg/m2

Exclusion Criteria:

All subjects will be excluded for the following reasons:

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
Uncontrolled hypertension
History or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [eGFR] <60 at screening)
History of pituitary or adrenal disorders or neuroendocrine tumor
Anemia defined as hematocrit <33% at screening
Active cancer diagnosis or currently undergoing cancer treatment
History of anorexia nervosa or previous gastrointestinal tract surgery
Pregnancy or lactation

Control subjects will be excluded for the following reasons:

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
Use of medications that alter insulin sensitivity (i.e. niacin, glucocorticoids, metformin)

Sites / Locations

Duke Center For Living

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Study Group: Type 2 Diabetes Mellitus (T2DM)

Control Group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Postprandial insulin secretion (ISR-meal)

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.

Index of β-cell sensitivity to glucose

Index of β-cell sensitivity to glucose will be calculated as incremental insulin/glucose (I/G) AUC (ΔAUCI/G).

Whole body insulin sensitivity using the Matsuda Index

The Matsuda Index is a well-known index of insulin sensitivity derived from several glucose and insulin values obtained during a mixed meal

β-cell function (DI-meal)

β-cell function (DI-meal) will be calculated as ΔAUCI/G x Matsuda Index

Secondary Outcome Measures

Full Information

NCT ID

NCT02440061

First Posted

May 7, 2015

Last Updated

March 29, 2018

Sponsor

Jenny Tong, MD, MPH

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT02440061

Brief Title

Ghrelin and Beta Cell Function in Diabetes

Official Title

Ghrelin Effect on Beta Cell Function in Health and Disease #2

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Withdrawn

Why Stopped

This protocol was replaced with a different one and therefore discontinued.

Study Start Date

May 2018 (Anticipated)

Primary Completion Date

June 2019 (Anticipated)

Study Completion Date

June 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Jenny Tong, MD, MPH

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

Ghrelin, age, BMI, and gender matched controls

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Study Group: Type 2 Diabetes Mellitus (T2DM)

Arm Type

Active Comparator

Arm Description

Arm Title

Control Group

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Synthetic human AG

Intervention Description

Synthetic human AG (0.28 μg/kg) bolus over 1 minute followed by 2 μg/kg/hr continuous infusion for 4.5 hours.

Intervention Type

Drug

Intervention Name(s)

Arginine

Intervention Description

Arginine hydrochloride (5 g) intravenously over 45 seconds.

Intervention Type

Drug

Intervention Name(s)

0.9% saline solution

Intervention Description

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

Primary Outcome Measure Information:

Title

Postprandial insulin secretion (ISR-meal)

Description

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.

Time Frame

approximately 8 weeks

Title

Index of β-cell sensitivity to glucose

Description

Index of β-cell sensitivity to glucose will be calculated as incremental insulin/glucose (I/G) AUC (ΔAUCI/G).

Time Frame

approximately 8 weeks

Title

Whole body insulin sensitivity using the Matsuda Index

Description

The Matsuda Index is a well-known index of insulin sensitivity derived from several glucose and insulin values obtained during a mixed meal

Time Frame

approximately 8 weeks

Title

β-cell function (DI-meal)

Description

β-cell function (DI-meal) will be calculated as ΔAUCI/G x Matsuda Index

Time Frame

approximately 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: T2DM study subjects to be considered for the study must meet the following inclusion criteria: Established T2DM with good to moderate glycemic control HbA1c < 8.5% Diabetes treatment with metformin, sulfonylurea, thiazolidinediones or combination of these medications; with no use of insulin during the study period 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: HbA1c ≤ 5.7% Fasting plasma glucose ≤ 95 mg/dL BMI ≤ 45.0 kg/m2 Exclusion Criteria: All subjects will be excluded for the following reasons: 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 Uncontrolled hypertension History or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [eGFR] <60 at screening) History of pituitary or adrenal disorders or neuroendocrine tumor Anemia defined as hematocrit <33% at screening Active cancer diagnosis or currently undergoing cancer treatment History of anorexia nervosa or previous gastrointestinal tract surgery Pregnancy or lactation Control subjects will be excluded for the following reasons: 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 Use of medications that alter insulin sensitivity (i.e. niacin, glucocorticoids, metformin)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jenny Tong, MD

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke Center For Living

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27705

Country

United States

12. IPD Sharing Statement

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Ghrelin and Beta Cell Function in Diabetes

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