Metabolic SyndromePhase 4NCT00666848
Effect of Sitagliptin and an ACE Inhibitor on Blood Pressure in Metabolic Syndrome
A Phase 4 study testing Enalapril 5mg, Enalapril 10mg and Sitagliptin in people with Metabolic Syndrome and Hypertension, run by Vanderbilt University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metabolic Syndrome, Hypertension
- What is being tested?
- Enalapril 5mg, Enalapril 10mg and Sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Jan 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Effect of Sitagliptin on the Blood Pressure Response to ACE Inhibition in the Metabolic Syndrome
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.
Read the 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.
- Conditions
- Metabolic Syndrome, Hypertension
- Being tested
- Placebo, Enalapril 5mg, Enalapril 10mg, Sitagliptin
- Keywords
- Metabolic syndrome, Hypertension, Sitagliptin, Enalapril
- Medical subject headings
- Metabolic Syndrome, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Enalapril 0mg after 5 days of placebo versus after 5 days sitagliptin 100mg/d
Enalapril 5mgDrug
Enalapril 5 mg after 5 days placebo versus after 5 days sitagliptin 100mg/d
Enalapril 10mgDrug
Enalapril 10mg after 5 days placebo versus after 5 days sitagliptin 100 mg/d
SitagliptinDrug
Sitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms.
| Study group | Role | What they receive |
|---|---|---|
| 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 . Receives: 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. Receives: 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. Receives: Drug: Enalapril 10mg; Drug: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: just prior to drug administration and 8 hours following treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2008 (estimated)
- Study startMar 2008
- Primary completionAug 2009
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nancy J. Brown, Vanderbilt University
- Investigators
- Nancy J Brown, M.D., Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00666848
- Sponsor's protocol ID
- 070977
- Status last verified
- Apr 2012
- First submitted
- 23 Apr 2008
- Last updated
- 11 May 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 20679179
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Sitagliptin on the Blood Pressure Response to ACE Inhibition in the Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT00666848
- Acronym / sponsor ID
- 070977
- Conditions
- Metabolic Syndrome, Hypertension
- Keywords
- Metabolic syndrome, Hypertension, Sitagliptin, Enalapril
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Mar 2008
- Primary completion
- Aug 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 25 Apr 2008 (estimated)
- Results
- Posted 11 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 2 (enalapril 5mg) | Placebo comparator | Drug: Enalapril 5mg, Drug: SitagliptinSubjects 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 . |
| 1 (placebo) | Placebo comparator | Drug: Placebo, Drug: SitagliptinSubjects 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. |
| 3 (enalapril 10mg) | Placebo comparator | Drug: Enalapril 10mg, Drug: SitagliptinSubjects 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Ambulatory subjects, 18 to 70 years of age, inclusive
- For female subjects, the following criteria must be met:
- Metabolic syndrome as defined by 3 or more of the following:
- Statin therapy for hypercholesterolemia must be a steady dose for 6 months prior to study day
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboEnalapril 0mg after 5 days of placebo versus after 5 days sitagliptin 100mg/d | Drug | 1 (placebo) |
| Enalapril 5mgEnalapril 5 mg after 5 days placebo versus after 5 days sitagliptin 100mg/d | Drug | 2 (enalapril 5mg) |
| Enalapril 10mgEnalapril 10mg after 5 days placebo versus after 5 days sitagliptin 100 mg/d | Drug | 3 (enalapril 10mg) |
| SitagliptinSitagliptin 100mg/day for 5 days crossed over to placebo daily for 5 days prior to arms. | Drug | 1 (placebo), 2 (enalapril 5mg), 3 (enalapril 10mg) |
Primary outcome
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20679179Marney 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy J Brown, M.D. principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Enalapril 5mg, Enalapril 10mg and Sitagliptin in people with Metabolic Syndrome and Hypertension, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in MAP During Placebo (time frame: just prior to drug administration and 8 hours after drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00666848, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2012.