Effects of Sitagliptin on Endothelial Function in Type 2 Diabetes on Background Metformin Therapy

NCT01859793 | Completed Phase 4 Results

• 1 other identifier: Merck-50600
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The study is being performed to determine whether sitagliptin, a dipeptidyl peptidase-4 inhibitor, both acutely and chronically improves blood vessel function. Patients with type 2 diabetes who are on metformin will be enrolled in this study for up to 22 weeks in this double blinded cross over study where they will receive a sitagliptin pill once a day for 8 weeks and during a separate 8 weeks receive a matching placebo pill. The treatment periods are divided by a 4 week period. Blood vessel function will be measured by ultrasound before and after a single dose of sitagliptin and placebo, as well as after 8 weeks of treatment with each. Blood will also be taken to measure blood markers of inflammation at each time the ultrasounds are performed.

Conditions

Diabetes; Atherosclerosis

Keywords

dipeptidyl peptidase-4 inhibitor; endothelium, vascular; diabetes type 2; nitric oxide; inflammation

Outcome Measures

Primary Outcomes (1)

• Brachial Artery Flow Mediated Dilation

  A measurement of endothelial function in humans

  Change before and after a single dose (2 hours post) and 8 weeks after daily dosing

Secondary Outcomes (2)

• Circulating Inflammatory Marker ICAM-1

  Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication

• Circulating Inflammatory Markers VCAM-1

  Change before and after acute dose (2 hours) and 8 weeks after daily dosing of medication

Study Arms (2)

Matching Placebo

PLACEBO COMPARATOR

Matching Placebo for Sitagliptin

Drug: Placebo

Sitagliptin

ACTIVE COMPARATOR

100mg pill, PO administered once daily.

Drug: sitagliptin

Interventions

sitagliptin DRUG

100 mg pill, administered once/day orally

Also known as: Januvia

Sitagliptin

Placebo DRUG

Matching placebo in appearance given once/day orally

Matching Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult age 21-70 years of age.
• Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
• On stable metformin therapy for at least 6 weeks prior to enrollment.
• Glycosylated Hemoglobin ≥6.2% and ≤ 9.5%.

You may not qualify if:

• History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 50% on angiography or by confirmed history of myocardial infarction by standard criteria.)
• Evidence of other evident major illness including chronic renal insufficiency (creatinine clearance less than 60 mL/min),chronic liver disease (AST or ALT greater than 2.5 x normal), or cancer currently undergoing systemic therapy or had systemic therapy for cancer within 1 year of enrollment.
• Pregnancy as determined by urinary beta-HCG test
• Illicit drug use (heroin, cocaine etc) in the past 1 year.
• Alcohol abuse, defined as the equivalent of 14 beers/week for a man or 7 beers/week for a woman
• History of allergy to DPP-4 inhibitors at the time of screening/enrollment
• Prior history of pancreatitis
• Patients currently on insulin or sulfonylurea therapy.
• Patients currently on digoxin.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Widlansky ME, Puppala VK, Suboc TM, Malik M, Branum A, Signorelli K, Wang J, Ying R, Tanner MJ, Tyagi S. Impact of DPP-4 inhibition on acute and chronic endothelial function in humans with type 2 diabetes on background metformin therapy. Vasc Med. 2017 Jun;22(3):189-196. doi: 10.1177/1358863X16681486. Epub 2017 Feb 1.

  PMID: 28145158 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Atherosclerosis; Diabetes Mellitus, Type 2; Inflammation

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Limitations and Caveats

No limitations noted.

Results Point of Contact

• Title: Michael E. Widlansky
• Organization: Medical College of Wisconsin

mwidlans@mcw.edu

414-955-6806

Study Officials

• Michael E Widlansky, MD, MPH

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: May 22, 2013
• Study Start: June 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: July 1, 2016
• Last Updated: October 21, 2016
• Results First Posted: October 21, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)