Ghrelin and Beta Cell Function in Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02440061
• Other study ID #: Pro00060865
• Secondary ID: R01DK097550
• Status: Withdrawn
• Phase: Phase 1
• First received: May 7, 2015
• Last updated: March 29, 2018
• Start date: May 2018
• Est. completion date: June 2019

Study information

• Verified date: March 2018
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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.
• Arginine
Arginine hydrochloride (5 g) intravenously over 45 seconds.
• 0.9% saline solution
A continuous infusion of 0.9% saline solution (control) for 4.5 hours.

Locations

Country	Name	City	State
United States	Duke Center For Living	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Jenny Tong, MD, MPH	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	approximately 8 weeks
Primary	Index of ß-cell sensitivity to glucose	Index of ß-cell sensitivity to glucose will be calculated as incremental insulin/glucose (I/G) AUC (?AUCI/G).	approximately 8 weeks
Primary	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	approximately 8 weeks
Primary	ß-cell function (DI-meal)	ß-cell function (DI-meal) will be calculated as ?AUCI/G x Matsuda Index	approximately 8 weeks