The Study of Exenatide Action on Vessel Function in Type 2 Diabetes and Prediabetes

NCT01181986 | Completed Phase 4 Results

• 1 other identifier: 1-10-CT-31
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this investigation is to evaluate whether exenatide, a type 2 diabetes medication, will improve the function of the innermost part of the arterial wall called the endothelium after a fat-enriched meal and to determine how this occurs. The results of this study will help to determine and understand a novel action of this group of diabetes medications based on the action of naturally occuring gut substances called incretins. This may have a significant impact on cardiovascular health in patients with early and longstanding diabetes.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 diabetes mellitus, Impaired glucose tolerance

Outcome Measures

Primary Outcomes (1)

• Reactive Hyperemia Index (RHI)

  Greater RHI reflects greater endothelial function. It is calculated as average post-ischemia pulse magnitude divided by average pre-ischemia pulse magnitude. Results are expressed as least-square means of ANCOVA models.

  0, 2, 4, 6 and 8 hours on Day 11 (Sub-study 1); 0 and 120 minutes on test Days 1, 2 & 3 (Sub-study 2)

Secondary Outcomes (2)

• Plasma Triglycerides

  0, 2, 4, 6 and 8 hours post-study drug on day 11

• Plasma Glucose

  0, 2, 4, 6, and 8 hours post-study drug on day 11

Study Arms (2)

Exenatide SC (Sub-study 1)

EXPERIMENTAL

Study groups will be individuals with recent onset (\<3 years) or established (\>5 years) T2D. The plan is to achieve 40 complete studies of subcutaneous injection of exenatide BID (Byetta®, 5 or 10 µg) or identically looking Placebo SC for 10 days, separated by 14-day washout period. On the next day after each treatment phase, a single dose of the assigned medication will be injected just before a fat-enriched breakfast meal. A lunch meal of similar caloric and nutrient content will be administered 4 hours following the breakfast meal. Endothelial function will be measured just prior to the injection and every 2 hours during 8-hour post-breakfast period.

Drug: Exenatide SC; Drug: Placebo SC

Exenatide IV (Sub-study 2)

EXPERIMENTAL

Study group will be individuals with recent onset (\<1 year) T2D on diet and impaired glucose tolerance. The plan is to achieve 35 complete studies. The intervention will include 3 randomly ordered visits with intravenous infusion of exenatide in the presence (v1) or absence (v2) of GLP-1 receptor inhibitor exendin-9, and a control test with Placebo IV without exendin-9 (v3). Endothelial function will be measured at baseline and 2 hours later during the final 15 minutes of the infusion cocktails. Study participants will remain fasting during the test visit (3 hours total).

Drug: Exenatide IV; Drug: Exendin-9; Drug: Placebo IV

Interventions

Exenatide SC DRUG

Exenatide 5-10 ug sc BID/10 days

Also known as: Byetta, exendin-4

Exenatide SC (Sub-study 1)

Exenatide IV DRUG

50 ng/min intravenously for 45 minutes on 2 out of 3 study visits separated by 5-10 days

Also known as: exendin-4, Byetta

Exenatide IV (Sub-study 2)

Placebo SC DRUG

Placebo sc BID/10days

Also known as: placebo

Exenatide SC (Sub-study 1)

Exendin-9 DRUG

Primed (6,000 pM/kg), continuous (600 pM/kg) intravenous infusion for 75 minutes on 1 out of 3 study visits.

Also known as: exendin-(9-39)

Exenatide IV (Sub-study 2)

Placebo IV DRUG

Intravenous infusion for 45 minutes on 1 out of 3 visits

Also known as: placebo

Exenatide IV (Sub-study 2)

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• US Veterans
• type 2 diabetes mellitus (T2D) diagnosed within 3 years with good glycemic control on diet, metformin, or sulfonylurea agents or combinations of these agents (HbA1c ≤8.0%)
• T2D diagnosed ≥ 5 years prior to study enrollment
• Impaired glucose tolerance

You may not qualify if:

• known or suspected T1D (early onset age, low body mass index, lack of family history)
• TZD use in the prior 3 months
• prior regular use of insulin
• Creatinine \>2.0 mg/dl or other laboratory or clinical evidence of kidney disease
• anemia
• known active liver disease or hepatic enzyme elevation two-and-a half times above normal
• acute bacterial or viral illness or evidence of other active infection in the past 4 weeks
• stable or unstable angina or other major illness in the past 6 months
• Raynaud's disease or any rheumatic disease affecting fingers
• current regular use of anti-inflammatory medications or antioxidants, including over the counter medications and high dose salicylates (\>1 g/day);
• subjects receiving lipid lowering or anti-hypertension medications must be on stable doses for at least 2 months prior to participation.

Sponsors & Collaborators

• Carl T. Hayden VA Medical Center: lead
• American Diabetes Association: collaborator
• Amylin Pharmaceuticals, LLC.: collaborator

Study Sites (1)

Phoenix VA Medical Center

Phoenix, Arizona, 85012, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance

Interventions

Exenatide; exendin (9-39)

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Dr. Juraj Koska
• Organization: Phoenix VA Health Care System

juraj.koska@va.gov

602-277-5551

Study Officials

• Juraj Koska, MD, PhD

  Phoenix VA Healthcare System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Health Scientist

Study Record Dates

• First Submitted: August 13, 2010
• First Posted: August 16, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 20, 2014
• Results First Posted: April 28, 2014

Record last verified: 2014-05

Locations

US (1)