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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00666848
First received: April 23, 2008
Last updated: April 12, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Metabolic Syndrome
Hypertension
Drug: Placebo
Drug: Enalapril 5mg
Drug: Enalapril 10mg
Drug: Sitagliptin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Sitagliptin on the Blood Pressure Response to ACE Inhibition in the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Change in MAP During Placebo [ Time Frame: just prior to drug administration and 8 hours after drug administration ] [ Designated as safety issue: Yes ]
    The change in mean arterial pressure (MAP) in response to placebo or enalapril after pretreatment with 5 days of placebo

  • Change in MAP During Sitagliptin [ Time Frame: just prior to drug administration and 8 hours following treatment ] [ Designated as safety issue: Yes ]
    Mean change in mean arterial pressure in response to placebo or enalapril in the presence of 5 days of sitagliptin 100mg/day


Enrollment: 24
Study Start Date: March 2008
Study Completion Date: January 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2 (enalapril 5mg)
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
Enalapril 5 mg after 5 days placebo versus after 5 days sitagliptin 100mg/d
Drug: Sitagliptin
Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.
Placebo Comparator: 1 (placebo)
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
Enalapril 0mg after 5 days of placebo versus after 5 days sitagliptin 100mg/d
Drug: Sitagliptin
Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.
Placebo Comparator: 3 (enalapril 10mg)
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
Enalapril 10mg after 5 days placebo versus after 5 days sitagliptin 100 mg/d
Drug: Sitagliptin
Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.

Detailed Description:

The prevalence of metabolic syndrome and Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in developed countries and is closely associated with hypertension. As new oral hypoglycemic agents become available for clinical use, practitioners wishing to treat both hyperglycemia and hypertension will use varieties of combinations of medications. In this setting, understanding interactions and additive effects of these medications becomes essential. Sitagliptin, a selective dipeptidyl peptidase-IV (DPP-4) inhibitor, improves glycemic control in patients with T2DM by decreasing the degradation of the incretin hormones. The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) augment nutrient mediated insulin release. To date there have been two reports of a blood pressure lowering effect of the DPP-4 inhibitor vildagliptin, but no mechanism for this effect has been proposed.

Specific Aim 1: To test the hypothesis that the DPP-4 inhibitor sitagliptin lowers blood pressure compared to placebo therapy in subjects with the metabolic syndrome.

Specific Aim 2: To test the hypothesis that the DPP-4 inhibitor sitagliptin potentiates the blood pressure response to acute ACE-inhibition.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • Hematocrit <35%
  • Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
  • Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
  • Treatment with lithium salts
  • History of alcohol or drug abuse
  • Treatment with any investigational drug in the 1 month preceding the study
  • Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
  • Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
  • Oral contraceptives
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00666848

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Nancy J Brown, M.D. Vanderbilt University
  More Information

Publications:
Responsible Party: Nancy J. Brown, Robert H. Williams Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00666848     History of Changes
Other Study ID Numbers: 070977
Study First Received: April 23, 2008
Results First Received: September 4, 2011
Last Updated: April 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Metabolic syndrome
Hypertension
Sitagliptin
Enalapril

Additional relevant MeSH terms:
Hypertension
Metabolic Syndrome X
Syndrome
Vascular Diseases
Cardiovascular Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Disease
Pathologic Processes
Sitagliptin
Enalapril
Enalaprilat
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 16, 2014