- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00666848
Effect of Sitagliptin and an ACE Inhibitor on Blood Pressure in Metabolic Syndrome
Effect of Sitagliptin on the Blood Pressure Response to ACE Inhibition in the Metabolic Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 .
|
Enalapril 5 mg after 5 days placebo versus after 5 days sitagliptin 100mg/d
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.
|
Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.
Enalapril 0mg after 5 days of placebo versus after 5 days sitagliptin 100mg/d
|
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.
|
Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.
Enalapril 10mg after 5 days placebo versus after 5 days sitagliptin 100 mg/d
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in MAP During Placebo
Time Frame: just prior to drug administration and 8 hours after drug administration
|
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
Time Frame: just prior to drug administration and 8 hours following treatment
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Nancy J Brown, M.D., Vanderbilt University Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Glucose Metabolism Disorders
- Metabolic Diseases
- Disease
- Insulin Resistance
- Hyperinsulinism
- Hypertension
- Syndrome
- Metabolic Syndrome
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Angiotensin-Converting Enzyme Inhibitors
- Enalaprilat
- Enalapril
- Sitagliptin Phosphate
Other Study ID Numbers
- 070977
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hypertension
-
National Taiwan University Hospital Hsin-Chu BranchRecruitingHypertension,Essential | Hypertension, MaskedTaiwan
-
University of Alabama at BirminghamTroy UniversityCompletedHypertension | Hypertension, Resistant to Conventional Therapy | Uncontrolled Hypertension | Hypertension, White CoatUnited States
-
BayerCompletedPrimary HypertensionChina
-
Columbia UniversityAgency for Healthcare Research and Quality (AHRQ)Active, not recruitingWhite Coat Hypertension | Hypertension,EssentialUnited States
-
Addpharma Inc.Completed
-
Universidade Federal de Santa MariaCompletedHealthy Volunteers | Hypertension, EssentialBrazil
-
Sheffield Teaching Hospitals NHS Foundation TrustUniversity of SheffieldCompletedIdiopathic Pulmonary Arterial Hypertension | Chronic Thromboembolic Pulmonary HypertensionUnited Kingdom
-
China Academy of Chinese Medical SciencesGuang'anmen Hospital of China Academy of Chinese Medical SciencesCompletedHypertension, Resistant to Conventional Therapy | Primary HypertensionChina
-
Cytos Biotechnology AGCompletedMild Essential Hypertension | Moderate Essential HypertensionSwitzerland
Clinical Trials on Enalapril 5mg
-
Ethicare GmbHUnknownHeart Failure | Dilated Cardiomyopathy | Congenital Heart DiseaseAustria, United Kingdom, Netherlands, Serbia, Hungary
-
Ethicare GmbHUnknownHeart Failure | Dilated CardiomyopathyAustria, United Kingdom, Hungary, Netherlands, Serbia
-
Eisai Co., Ltd.Completed
-
Ethicare GmbHUnknownHeart Failure | Congenital Heart DiseaseAustria, United Kingdom, Hungary, Netherlands, Serbia
-
University of EdinburghNHS LothianCompleted
-
Vigonvita Life SciencesCompletedErectile DysfunctionChina
-
Boehringer IngelheimCompleted
-
Yuhan CorporationActive, not recruitingHypertension | HypercholesterolemiaKorea, Republic of
-
Dong-A ST Co., Ltd.CompletedThe Pharmacokinetics/Pharmacodynamics and Safety/Tolerability of Evogliptin in Hemodialysis PatientsHemodialysis PatientsKorea, Republic of
-
Shenzhen Ausa Pharmed Co.,LtdAnhui Medical UniversityCompleted