Ghrelin and Beta Cell Function in Diabetes

Jenny Tong, MD, MPH

Status and phase: Withdrawn; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Synthetic human AG; Drug: 0.9% saline solution; Drug: Arginine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02440061

R01DK097550 (U.S. NIH Grant/Contract)

Pro00060865

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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0 participants in 2 patient groups

Study Group: Type 2 Diabetes Mellitus (T2DM)

Active Comparator group

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.

Treatment:

Drug: 0.9% saline solution

Drug: Arginine

Drug: Synthetic human AG

Control Group

Active Comparator group

Description:

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.

Treatment:

Drug: 0.9% saline solution

Drug: Arginine

Drug: Synthetic human AG