Effects of DPP-4 Inhibition on Triglycerides

Sponsor

Oregon Health and Science University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01527747

Collaborator

(none)

Enrollment

Location

Arms

107

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to test the effects of saxagliptin, a treatment for diabetes, on fasting and post-meal blood triglyceride (blood fat) levels.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Hypertriglyceridemia	Drug: Saxagliptin	Phase 4

Detailed Description

This study is designed to help us understand the effects of DPP-4 inhibition on triglyceride levels before and after eating.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Effects of Dipeptidyl Peptidase-4 Inhibition With Saxagliptin on Fasting and Postprandial Triglyceride Concentrations

Study Start Date :

Jan 1, 2012

Anticipated Primary Completion Date :

Nov 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo arm	Drug: Saxagliptin 5 mg daily Other Names: Onglyza
Experimental: Saxagliptin Active drug arm	Drug: Saxagliptin 5 mg daily Other Names: Onglyza

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo arm

Drug: Saxagliptin

5 mg daily

Other Names:

Onglyza

Experimental: Saxagliptin

Active drug arm

Drug: Saxagliptin

5 mg daily

Other Names:

Onglyza

Outcome Measures

Primary Outcome Measures

Change in fasting and postprandial triglyceride concentrations [baseline, 6 weeks]
Comparison of 6 weeks of placebo vs 6 weeks of saxagliptin

Secondary Outcome Measures

Changes in glycemia [baseline, 6 weeks]
Comparison of 6 weeks of placebo vs 6 weeks of saxagliptin

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Willing to provide signed written informed consent
Men and women aged 18-80 years
Type 2 diabetes (as defined by the ADA - see reference 18)
Baseline HgbA1c between 6.5% and 8%; HgbA1c 7.5-8.0% among subjects taking sulfonylureas
Baseline plasma triglyceride concentration between 200 and 700 mg/dl
Stable diabetes medication regimen for at least 12 weeks prior to study entry
Taking a statin for at least 8 weeks, unless statin therapy is contraindicated or intolerable
Treatment with other lipid-lowering medications only if the dose has been stable for > 8 weeks.
Non-smoker
Body mass index < 45.0 kg/m2
BP < 140/85
Normal serum TSH and free T4 concentrations (hypothyroid subjects taking a stable replacement dose of levothyroxine will be allowed if they are biochemically euthyroid)
Subjects will otherwise be healthy
Women of child-bearing potential must be willing to use reliable contraception, as defined by our IRB, throughout the study (There are currently no FDA recommended restrictions on the use of saxagliptin in sexually active men, or requirements for contraception in their wives or sexual partners)
Able and willing to complete study procedures

Exclusion Criteria:

Transaminase concentrations > 2 times the ULN. (Mild elevations of AST and ALT will be allowed up to 2x ULN at baseline if there is no evidence of viral hepatitis or intrinsic liver disease. Since many of these subjects may have some degree of hepatic steatosis, a key intervention is the implementation of treatment to lower glucose and triglycerides)
Estimated creatinine clearance < 60 ml/min
Microalbumin-creatinine ratio > 120
Alcohol consumption > 1 drink daily in women and > 2 drinks daily in men
Pancreatitis within the preceding 6 months
Type 1 diabetes
History of diabetic ketoacidosis (DKA)
Cardiovascular disease (CAD, stroke, PVD)
Known human immunodeficiency virus (HIV) infection
Viral hepatitis
Pregnancy or lactation
A current diagnosis of active non-dermatologic cancer
Other life-threatening illness
History of small bowel resection or gastric bypass surgery
Use of glucocorticoid medications, beta blockers, thiazide diuretics, excess alcohol intake (beta-blockers and thiazide diuretic will be allowed, if necessary, if the dose has been stable for > 12 weeks prior to study entry and the dose will remain stable throughout the study. Complete exclusion of these drugs would exclude a substantial proportion of diabetic patients)
Use of systemic cytochrome P450 3A4 (CYP 3A4/5) inhibitors such as ketaconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir and telithromycin.
Current enrollment in another research study or use of any investigational drug within 90 days of study entry
Other medical conditions that may interfere with participation in the study, in the opinion of the investigator