Effect of Sitagliptin and an ACE Inhibitor on Blood Pressure in Metabolic Syndrome

NCT00666848 | Completed Phase 4 Results

• 1 other identifier: 070977
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study will measure the effect of the anti-diabetic agent sitagliptin on blood pressure in individuals with the metabolic syndrome. We will also measure the effect of sitagliptin on blood pressure in people already taking a blood pressure medication called an ACE inhibitor.

Conditions

Metabolic Syndrome; Hypertension

Keywords

Metabolic syndrome; Hypertension; Sitagliptin; Enalapril

Outcome Measures

Primary Outcomes (2)

• Change in MAP During Placebo

  The change in mean arterial pressure (MAP) in response to placebo or enalapril after pretreatment with 5 days of placebo

  just prior to drug administration and 8 hours after drug administration

• Change in MAP During Sitagliptin

  Mean change in mean arterial pressure in response to placebo or enalapril in the presence of 5 days of sitagliptin 100mg/day

  just prior to drug administration and 8 hours following treatment

Study Arms (3)

2 (enalapril 5mg)

PLACEBO COMPARATOR

Subjects received Enalapril 5mg on study day and a placebo pill for 5 days prior or subjects received enalapril 5mg on study day and sitagliptin 100mg/day for 5 days prior .

Drug: Enalapril 5mg; Drug: Sitagliptin

1 (placebo)

PLACEBO COMPARATOR

Subjects received a placebo pill on study day and received a placebo pill for 5 days prior or subjects received a Placebo pill on study day and sitagliptin 100mg for 5 days prior.

Drug: Placebo; Drug: Sitagliptin

3 (enalapril 10mg)

PLACEBO COMPARATOR

Subjects received Enalapril 10mg on study day and a placebo pill for 5 days prior, or subjects received Enalapril 10mg on study day and sitagliptin 100mg for 5 days prior.

Drug: Enalapril 10mg; Drug: Sitagliptin

Interventions

Placebo DRUG

Enalapril 0mg after 5 days of placebo versus after 5 days sitagliptin 100mg/d

1 (placebo)

Enalapril 5mg DRUG

Enalapril 5 mg after 5 days placebo versus after 5 days sitagliptin 100mg/d

2 (enalapril 5mg)

Enalapril 10mg DRUG

Enalapril 10mg after 5 days placebo versus after 5 days sitagliptin 100 mg/d

3 (enalapril 10mg)

Sitagliptin DRUG

Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.

1 (placebo); 2 (enalapril 5mg); 3 (enalapril 10mg)

Eligibility Criteria

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

You may qualify if:

• Ambulatory subjects, 18 to 70 years of age, inclusive
• For female subjects, the following criteria must be met:
• Postmenopausal for at least 1 year, or
• Status-post surgical sterilization, or
• If of childbearing potential, utilization of barrier contraceptive and willingness to undergo beta-hcg testing prior to drug treatment and on every study day
• Metabolic syndrome as defined by 3 or more of the following:
• Fasting plasma glucose of at least 100 mg/dL (5.6 mmol/L)
• Serum triglycerides of at least 150 mg/dL (1.7 mmol/L)
• Serum HDL less than or equal to 40 mg/dL in men or less than 50 mg/dL in women or on cholesterol-lowering medications
• Blood pressure of at least 130/85 mmHg or on blood-pressure lowering medications
• Waist girth of more than 102 cm in med or 88 cm in women
• Statin therapy for hypercholesterolemia must be a steady dose for 6 months prior to study day

You may not qualify if:

• Diabetes type 1 or type 2, as defined by a fasting glucose of 126 mg/dL or greater or the use of anti-diabetic medication
• History of reported or recorded hypoglycemia (plasma glucose less than 70 mg/dL)
• Use of hormone replacement therapy
• In hypertensive patients, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg
• Pregnancy
• Breast-feeding
• Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
• Treatment with anticoagulants
• History of serious neurological disease such as cerebral hemorrhage, stroke, or transient ischemic attack
• History or presence of immunological or hematological disorders
• Diagnosis of current asthma
• History of angioedema associated with use of ACE-I
• Clinically significant gastrointestinal impairment that could interfere with drug absorption
• Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transferase \[ALT\] \> 2.0 x upper limit of normal range)
• Impaired renal function (serum creatinine \> 1.5 mg/dl)

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Marney A, Kunchakarra S, Byrne L, Brown NJ. Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensin-converting enzyme inhibition in humans. Hypertension. 2010 Oct;56(4):728-33. doi: 10.1161/HYPERTENSIONAHA.110.156554. Epub 2010 Aug 2.

  PMID: 20679179 RESULT

MeSH Terms

Conditions

Metabolic Syndrome; Hypertension

Interventions

Enalapril; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Nancy J. Brown, M.D.
• Organization: Vanderbilt University School of Medicine

nancy.j.brown@vanderbilt.edu

615-343-8701

Study Officials

• Nancy J Brown, M.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• 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: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Robert H. Williams Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: April 23, 2008
• First Posted: April 25, 2008
• Study Start: March 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: January 1, 2010
• Last Updated: May 11, 2012
• Results First Posted: May 11, 2012

Record last verified: 2012-04

Locations

US (1)