Ghrelin and Beta Cell Function in Diabetes

NCT ID: NCT02440061

Last Updated: 2018-04-02

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-31
• Study Completion Date: 2019-06-30

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Synthetic human AG

Intervention Type: DRUG

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

Arginine

Intervention Type: DRUG

Arginine hydrochloride (5 g) intravenously over 45 seconds.

0.9% saline solution

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Synthetic human AG

Intervention Type: DRUG

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

Arginine

Intervention Type: DRUG

Arginine hydrochloride (5 g) intravenously over 45 seconds.

0.9% saline solution

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Arginine

Arginine hydrochloride (5 g) intravenously over 45 seconds.

Intervention Type: DRUG

0.9% saline solution

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

Intervention Type: DRUG

Eligibility Criteria

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

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: collaborator

Jenny Tong, MD, MPH

OTHER

Sponsor Role: lead

Responsible Party

Jenny Tong, MD, MPH

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jenny Tong, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke Center For Living

Durham, North Carolina, United States

Countries

United States

Other Identifiers

R01DK097550

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00060865

Identifier Type: -

Identifier Source: org_study_id