Ghrelin and Beta Cell Function in Diabetes

Phase 1

Withdrawn

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Synthetic human AG; Drug: Arginine; Drug: 0.9% saline solution

• Registration Number: NCT02440061
• Lead Sponsor: Jenny Tong, MD, MPH

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-05-07
• Study First Submitted QC: 2015-05-08
• Study First Posted: 2015-05-12
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-29
• Last Update Posted: 2018-04-02
• Study Start: 2018-05
• Primary Completion: 2019-06
• Study Completion: 2019-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Group: Type 2 Diabetes Mellitus (T2DM)	Synthetic human AG	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.
Study Group: Type 2 Diabetes Mellitus (T2DM)	Arginine	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.
Study Group: Type 2 Diabetes Mellitus (T2DM)	0.9% saline solution	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	Synthetic human AG	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.
Control Group	0.9% saline solution	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.
Control Group	Arginine	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.

Primary Outcome Measures

Name	Time	Method
Index of β-cell sensitivity to glucose	approximately 8 weeks	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	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
Postprandial insulin secretion (ISR-meal)	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.
β-cell function (DI-meal)	approximately 8 weeks	β-cell function (DI-meal) will be calculated as ΔAUCI/G x Matsuda Index

Trial Locations

Locations (1)

Duke Center For Living; 🇺🇸 Durham, North Carolina, United States