HypertensionPhase 2/3NCT02235519
Pleiotropic Effects of Azilsartan Medoxomil Over Insulin Resistance in Obese, Diabetic and Hypertensive Patients
A Phase 2/3 study testing Azilsartan 40 mg. and Azilsartan 80 mg in people with Hypertension and Obesity, run by Hospital General de México Dr. Eduardo Liceaga at 1 site in Mexico.
Trial summary
The goal of this study is to build a mathematical model to explain the effect of two doses of azilsartan (40 and 80 mg) upon metabolic (insulin resistance, glucose) and inflammatory parameters (cytokines) in function of "metabolic strata" like obesity, type 2 diabetes mellitus, hypertension and their combinations. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Obesity, Type 2 Diabetes Mellitus
- What is being tested?
- Azilsartan 40 mg. and Azilsartan 80 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteMexico
- Study dates
- Jan 2014to Jun 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent in accordance with Good Clinical Practices and local legislations
- Age between ≥25 and ≤ 65 years
- Patients with hypertension stage 1 as defined by systolic blood pressure (SBP) ≥140 but <159 mmHg and diastolic blood pressure (DBP) ≥90 but < 99 mmHg at randomization
- Ability to stop any current antihypertensive therapy without unacceptable risk to the patient (Investigator's discretion)
- BMI ≥25 and ≤35.
- Patients with type 2 diabetes mellitus can participate and will be stratified before randomization. Diagnosis can be established by clinical history, 75-g oral glucose tolerance test (ADA criteria), or fasting glucose > 126 mg/dL.
Who cannot join
- Pre-menopausal women (last menstruation ≤1 year prior to signing informed consent) who are not surgically sterile, nursing, are pregnant or without any anticonceptive methods.
- Known hypersensitivity to the study drug
- Gastrointestinal surgery which might alter absorption, distribution, or drug metabolism.
- History of angioedema related to ACE inhibitors or angiotensin II receptor blockers.
- Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m.
- Known or suspected secondary hypertension (e.g., renal artery stenosis or phaeochromocytoma)
Show all 25Show fewer
- SBP≥160 mmHg and/or DBP ≥100 mmHg
- Renal dysfunction as defined by: serum creatinine >3.0 mg/dL (or >265 umol/L) and/or creatinine clearance <30 ml/min and/or other clinical markers of severe renal impairment.
- Bilateral renal arterial stenosis, renal artery stenosis in a solitary functional kidney, post-renal transplant patients or patients with one kidney
- Clinically relevant hypokalemia or hyperkalemia (i.e., <3.5 mmol/L or >5.5 mmol/L, may be rechecked for suspected error in result)
- Uncorrected sodium or volume depletion
- Primary aldosteronism.
- Hereditary fructose intolerance
- Biliary obstructive disorders (e.g., cholestasis) or hepatic insufficiency
- Congestive heart failure class III-IV according to criteria fron the New York Heart Association.
- Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the Investigator.
- Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve
- Patients whose diabetes has not been stable and controlled for at least the past 3 months as defined by an Glycosylated Hemoglobin A1c >=10% or fasting glucose greater than 400 mg/dL.
- Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin-II receptor antagonists
- History of drug or alcohol dependency within 6 months prior to signing the informed consent form
- Concomitant administration of any medications known to affect blood pressure, except medications allowed by the protocol
- Any investigational drug therapy within 1 month of signing the informed consent
- Known hypersensitivity to any component of the trial drugs (telmisartan, hydrochlorothiazide, or placebo)
- History of non-compliance or inability to comply with prescribed medications or protocol procedures (less than 80% or more than 120%, especially during run-in).
- Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the trial medication
Trial locations and contacts
1 site in 1 country.
Mexico1 site, 1 recruiting
- Recruiting
Hospital General de Mexico "Dr. Eduardo Liceaga"
Mexico City, Mexico City, 06720
Juan A Peralta, bachelor
About this study
Official title: A Randomized, Open Label Study to Evaluate the Pleiotropic Effects of Azilsartan Medoxomil 40 and 80 mg for 12 Weeks Over Metabolic Markers in Patients With Hypertension, Obesity or Type 2 Diabetes Mellitus
The goal of this study is to build a mathematical model to explain the effect of two doses of azilsartan (40 and 80 mg) upon metabolic (insulin resistance, glucose) and inflammatory parameters (cytokines) in function of "metabolic strata" like obesity, type 2 diabetes mellitus, hypertension and their combinations.
Read the detailed description
There are data supporting angiotensin II receptor subtype 1 (AT1) antagonist have beneficial effects on metabolic control due to some pleiotropic effect mediated by peroxisome proliferator-activated receptor (PPAR) gamma induction. Azilsartan is a prodrug absorbed in the gastrointestinal tract that can improve metabolic milieu under diverse conditions like obesity, hypertension (can be considered a metabolic disease) or type 2 diabetes mellitus. Clinical studies that have been raised in this regard are few, and still show controversial issues.
The objective of any study with AT1 antagonist drug interested in pleiotropic effects should not only focus on antihypertensive improvement, but also the effect on other areas such as metabolism of lipids and carbohydrates in obese and/or type 2 diabetes.
This study is a randomized, open labeled, clinical study. The aim is to build a mathematical model for supporting the effect of azilsartan 40 or 80 mg on metabolic and inflammatory measurements in function of metabolic conditions (i.e. obesity, type 2 diabetes and hypertension, and their combinations).
Patients will be stratified according to their metabolic status and randomized by blocks of four for each strata. This strategy will help to maintain each treatment group in balance. All subjects will receive the treatment for 12 weeks.
Subjects who attend the outpatient consultation at the Hospital General de Mexico will be invited to participate in the study. Those who meet the inclusion criteria must sign an informed consent approved by the ethics committee. This document describes the follow-up visits as described below:
Screening visit (V-1):
This visit includes patient history, physical examination (weight, height, waist circumference and blood pressure) and a blood sample for measurement of: complete blood count, fasting glucose, HbA1c, creatinine, adiponectin, IL-1b, IL-6, IL-10, TNF-α, liver function tests, C-reactive protein, blood chemistry, proteinuria, 24-hours urinary glucose and creatinine.
Initial visit (V0):
Physical examination will be performed and blood samples for oral glucose tolerance test will be drawn at 0, 30, 60, 90 and 120 minutes, with these data points the Matsuda insulin sensitivity index will be calculated. Pharmacological treatment of 40mg or 80mg azilsartan 4 weeks will be assigned (open labeled but randomized).
Visit 1 and 2 (V1, V2):
These visits performed at 4 and 8 weeks respectively include: physical examination, recording of adverse events and medication count to check adherence to treatment accomplishment.
Visit 3 (V3):
Week 12 include physical examination, adverse events registration, complete blood count, fasting glucose, HbA1c, creatinine, adiponectin, IL-1b, IL-6, IL-10, TNF - α, liver function tests, C reactive protein, blood chemistry, proteinuria, 24-hours urinary glucose and creatinine. Furthermore an oral glucose tolerance test with samples at 0, 30, 60, 90 and 120 minutes will be taken, to calculate the index of insulin sensitivity by the Matsuda method.
Statistical analysis and sample size. The sample size was calculated for ANCOVA analysis considering 8 groups with 5 covariates. Considering an alpha error of 5%, effect size of 30%, and statistical power of 90% a total sample of 250 patient was calculated. If we consider a 20% attrition of the sample, giving a total of 300 patients, i.e. 150 patients per treatment group.
A descriptive analysis will be done. The contrast among groups will be analyzed by an ANCOVA model and the function fitness will be calculated using ordinary least squares. Dependent variables will be insulin sensitivity, proteinuria, stiffness of the carotid artery, cytokines. Fixed factors: sex, blood pressure category, metabolic status, drug treatment. Covariates: Age, waist circumference.
The greatest expected size of effect would be within the group of patients with obesity, hypertension, and type 2 diabetes mellitus (all three) treated with 80 mg and the lowest size of effect within the group of only obesity treated with 40 mg.
- Conditions
- Hypertension, Obesity, Type 2 Diabetes Mellitus
- Being tested
- Azilsartan 40 mg., Azilsartan 80 mg
- Medical subject headings
- Hypertension, Obesity, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azilsartan 40 mg.Drug
Also called Edarbi 40 mg
Patients will take 40 mg of azilsartan during 12 weeks
Azilsartan 80 mgDrug
Also called Edarbi 80 mg
Patients will take 80 mg of azilsartan during 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Azilsartan low dosage | Active comparator | Patients will take azilsartan 40 mg during 12 weeks Receives: Drug: Azilsartan 40 mg. |
| Azilsartan high dosage | Active comparator | Patients will take azilsartan 80 mg during 12 weeks Receives: Drug: Azilsartan 80 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood pressure
Effect size of azilsartan medoxomil 40 and 80 mg in lowering systolic and diastolic blood pressure stratified by metabolic condition (obesity or type 2 diabetes mellitus). The minimal size effect between groups will be at least 30% and absolute percentage of previous hypertensive subjects reaching targeted values of < 130/85 mmHg.
Measured: 12 weeks
Secondary outcomes (4)
Insulin sensitivity and HbA1c level
Effect over insulin sensitivity measured by Matsuda index of insulin sensitivity (ISI) and the level of HbA1c. The function will show a increase for ISI that in a within contrast will be larger for those with obesity with hypertension and diabetes. Meanwhile the HbA1 will show a deep decrease for the same group.
Measured: 12 weeks
Effect of azilsartan on Inflammatory markers
Effect size between azilsartan 40 mg and 80 mg on inflammatory markers (IL-1b, IL-6, IL 10, TNF-α, and adiponectin). A decrease in this response will be more important for the 80 mg and those with obesity, hipertension and diabetes.
Measured: 12 weeks
Endothelial function
Subjects with stiffness of the carotid and brachial artery will show improvement in relaxation, and the larger effect will be for 80 mg in the group of obesity, hypertension and diabetes mellitus.
Measured: 12 weeks
Renal function improvement.
Proteinuria will show a significant decrease after 12 weeks of treatment with azilsartan. The larger effect will be for the 80 mg and the obese, hypertension and diabetic group.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2014 (estimated)
- Study startJan 2014
- Primary completionJun 2015 (estimated)
- Study completionJun 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital General de México Dr. Eduardo Liceaga
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Antonio Peralta, MD, Principal investigator, HGMRogelio Zapata, MD, Study chair, HGMEstrella Martinez, RN, Study director, HGM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02235519
- Sponsor's protocol ID
- DI/12/404B/4/85
- Status last verified
- Sep 2014
- First submitted
- 5 Sep 2014
- Last updated
- 30 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label Study to Evaluate the Pleiotropic Effects of Azilsartan Medoxomil 40 and 80 mg for 12 Weeks Over Metabolic Markers in Patients With Hypertension, Obesity or Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02235519
- Acronym / sponsor ID
- DI/12/404B/4/85
- Conditions
- Hypertension, Obesity, Type 2 Diabetes Mellitus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Hospital General de México Dr. Eduardo LiceagaOther government
- Study start
- Jan 2014
- Primary completion
- Jun 2015 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 10 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to build a mathematical model to explain the effect of two doses of azilsartan (40 and 80 mg) upon metabolic (insulin resistance, glucose) and inflammatory parameters (cytokines) in function of "metabolic strata" like obesity, type 2 diabetes mellitus, hypertension and their combinations.
Detailed description
There are data supporting angiotensin II receptor subtype 1 (AT1) antagonist have beneficial effects on metabolic control due to some pleiotropic effect mediated by peroxisome proliferator-activated receptor (PPAR) gamma induction. Azilsartan is a prodrug absorbed in the gastrointestinal tract that can improve metabolic milieu under diverse conditions like obesity, hypertension (can be considered a metabolic disease) or type 2 diabetes mellitus. Clinical studies that have been raised in this regard are few, and still show controversial issues.
The objective of any study with AT1 antagonist drug interested in pleiotropic effects should not only focus on antihypertensive improvement, but also the effect on other areas such as metabolism of lipids and carbohydrates in obese and/or type 2 diabetes.
This study is a randomized, open labeled, clinical study. The aim is to build a mathematical model for supporting the effect of azilsartan 40 or 80 mg on metabolic and inflammatory measurements in function of metabolic conditions (i.e. obesity, type 2 diabetes and hypertension, and their combinations).
Patients will be stratified according to their metabolic status and randomized by blocks of four for each strata. This strategy will help to maintain each treatment group in balance. All subjects will receive the treatment for 12 weeks.
Subjects who attend the outpatient consultation at the Hospital General de Mexico will be invited to participate in the study. Those who meet the inclusion criteria must sign an informed consent approved by the ethics committee. This document describes the follow-up visits as described below:
Screening visit (V-1):
This visit includes patient history, physical examination (weight, height, waist circumference and blood pressure) and a blood sample for measurement of: complete blood count, fasting glucose, HbA1c, creatinine, adiponectin, IL-1b, IL-6, IL-10, TNF-α, liver function tests, C-reactive protein, blood chemistry, proteinuria, 24-hours urinary glucose and creatinine.
Initial visit (V0):
Physical examination will be performed and blood samples for oral glucose tolerance test will be drawn at 0, 30, 60, 90 and 120 minutes, with these data points the Matsuda insulin sensitivity index will be calculated. Pharmacological treatment of 40mg or 80mg azilsartan 4 weeks will be assigned (open labeled but randomized).
Visit 1 and 2 (V1, V2):
These visits performed at 4 and 8 weeks respectively include: physical examination, recording of adverse events and medication count to check adherence to treatment accomplishment.
Visit 3 (V3):
Week 12 include physical examination, adverse events registration, complete blood count, fasting glucose, HbA1c, creatinine, adiponectin, IL-1b, IL-6, IL-10, TNF - α, liver function tests, C reactive protein, blood chemistry, proteinuria, 24-hours urinary glucose and creatinine. Furthermore an oral glucose tolerance test with samples at 0, 30, 60, 90 and 120 minutes will be taken, to calculate the index of insulin sensitivity by the Matsuda method.
Statistical analysis and sample size. The sample size was calculated for ANCOVA analysis considering 8 groups with 5 covariates. Considering an alpha error of 5%, effect size of 30%, and statistical power of 90% a total sample of 250 patient was calculated. If we consider a 20% attrition of the sample, giving a total of 300 patients, i.e. 150 patients per treatment group.
A descriptive analysis will be done. The contrast among groups will be analyzed by an ANCOVA model and the function fitness will be calculated using ordinary least squares. Dependent variables will be insulin sensitivity, proteinuria, stiffness of the carotid artery, cytokines. Fixed factors: sex, blood pressure category, metabolic status, drug treatment. Covariates: Age, waist circumference.
The greatest expected size of effect would be within the group of patients with obesity, hypertension, and type 2 diabetes mellitus (all three) treated with 80 mg and the lowest size of effect within the group of only obesity treated with 40 mg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azilsartan low dosage | Active comparator | Drug: Azilsartan 40 mg.Patients will take azilsartan 40 mg during 12 weeks |
| Azilsartan high dosage | Active comparator | Drug: Azilsartan 80 mgPatients will take azilsartan 80 mg during 12 weeks |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent in accordance with Good Clinical Practices and local legislations
- Age between ≥25 and ≤ 65 years
- Patients with hypertension stage 1 as defined by systolic blood pressure (SBP) ≥140 but <159 mmHg and diastolic blood pressure (DBP) ≥90 but < 99 mmHg at randomization
- Ability to stop any current antihypertensive therapy without unacceptable risk to the patient (Investigator's discretion)
- BMI ≥25 and ≤35.
Key exclusion criteria (25 listed)
- Pre-menopausal women (last menstruation ≤1 year prior to signing informed consent) who are not surgically sterile, nursing, are pregnant or without any anticonceptive methods.
- Known hypersensitivity to the study drug
- Gastrointestinal surgery which might alter absorption, distribution, or drug metabolism.
- History of angioedema related to ACE inhibitors or angiotensin II receptor blockers.
- Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m.
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 |
|---|---|---|
| Azilsartan 40 mg.Also: Edarbi 40 mgPatients will take 40 mg of azilsartan during 12 weeks | Drug | Azilsartan low dosage |
| Azilsartan 80 mgAlso: Edarbi 80 mgPatients will take 80 mg of azilsartan during 12 weeks | Drug | Azilsartan high dosage |
Primary outcome
Blood pressure
Time frame: 12 weeks
Effect size of azilsartan medoxomil 40 and 80 mg in lowering systolic and diastolic blood pressure stratified by metabolic condition (obesity or type 2 diabetes mellitus). The minimal size effect between groups will be at least 30% and absolute percentage of previous hypertensive subjects reaching targeted values of < 130/85 mmHg.
4 secondary outcomes
Insulin sensitivity and HbA1c level
Time frame: 12 weeks
Effect of azilsartan on Inflammatory markers
Time frame: 12 weeks
Endothelial function
Time frame: 12 weeks
Renal function improvement.
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2015.
Related trials for Hypertension
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
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.
Antonio Peralta, MD principal investigator
HGM
Rogelio Zapata, MD study chair
HGM
Estrella Martinez, RN study director
HGM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Azilsartan 40 mg. and Azilsartan 80 mg in people with Hypertension and Obesity, run by Hospital General de México Dr. Eduardo Liceaga at 1 site in Mexico.
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 6 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 30 Mar 2015. 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 Mexico. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antonio Peralta, MD (521(55)43466306, juan_peca@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood pressure (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Mar 2015.