High Blood PressurePhase 2NCT00417170

Comparison of Aliskiren and Amlodipine on Insulin Resistance and Endothelial Dysfunction in Patients With Hypertension and Metabolic Syndrome

A Phase 2 study testing Aliskiren and Amlodipine in people with High Blood Pressure and Metabolic Syndrome, run by Novartis Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study was to determine the effects of Aliskiren on insulin resistance (IR) and endothelial dysfunction (ED) in patients with high blood pressure and metabolic syndrome. The efficacy of Aliskiren was compared to Amlodipine. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: High Blood Pressure, Metabolic Syndrome, Insulin Resistance
What is being tested?: Aliskiren and Amlodipine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 48 participants
Where: 1 siteUnited States
Study dates: Oct 2007to Jul 2010
Phase: Phase 2
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female adults aged 18 to 55 years, inclusive.
Sitting diastolic blood pressure ≥80 mm Hg and/or sitting systolic blood pressure ≥ 130 at screening.
Metabolic Syndrome as defined by the Adult Treatment Panel (ATP) III criteria.
Hypertension (defined above) and impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) plus one or more out of the remaining 3 criteria to satisfy entry into the study. IGT and IFG will be classified according to American Diabetes Association (ADA) guidelines:
IFG: Fasting plasma glucose of 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9 mmol/l)
IGT: Two-hour plasma glucose of 140 mg/dl (7.8 mmol/l) to 199 mg/dl (11.0 mmol/l)

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Abnormal Positron Emission Tomography (PET) results at baseline. (Myocardial Blood Flow (MBF) of less than or equal to 35%.)
Abnormal euglycemic clamp results at baseline. (Glucose infusion rate (GINF) of less than or equal to 4.2 mg/kg/min.)
Body mass index (BMI) of less than 40.

Who cannot join

Smokers (use of tobacco products in the recent past)
Cardiovascular abnormalities including myocardial infarction, angina pectoris, hypertensive encephalopathy, stroke, transient ischemic attack, valvular heart disease, ventricular arrhythmia, A-V block, atrial fibrillation or cardiac revascularization/angioplasty in the past 12 months.
Symptoms or clinical evidence of congestive heart failure or known left ventricular ejection fraction < 40%.
Supine Blood pressure ≥ 160 mmHg systolic or ≥110 mmHg diastolic.
Clinically significant echocardiogram (ECG) abnormalities, including history of a prolonged QT-interval syndrome.
Significant autonomic dysfunction.

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Severe bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
Clinically significant drug allergy, atopic allergy (asthma, urticaria, eczematous dermatitis).
Pregnant or breastfeeding females. Pre-menopausal females who are not practicing a non-hormonal method of birth control.
African Americans will not be eligible for this study.
Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site

Novartis Investigative Site
Santa Monica, California, 90404

Other trials in United States

About this study

Official title: A Double-blind, Double Dummy, Randomized Parallel Design Trial to Study the Effects of 12 Weeks of Treatment With 300mg Aliskiren vs. 5mg Amlodipine on Insulin Resistance and Endothelial Dysfunction in Hypertensive Patients With Metabolic Syndrome

Conditions: High Blood Pressure, Metabolic Syndrome, Insulin Resistance, Endothelial Dysfunction
Being tested: Aliskiren, Amlodipine, Placebo Aliskiren, Placebo Amlodipine
Keywords: High Blood pressure, Hypertension, metabolic syndrome, insulin resistance, endothelial dysfunction, pre-diabetic, amlodipine,, aliskiren,, IGT,, IFG,, MBF
Medical subject headings: Hypertension, Metabolic Syndrome, Insulin Resistance, Glucose Intolerance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AliskirenDrug
Aliskiren 300 mg tablets taken orally once daily
AmlodipineDrug
Amlodipine 5 mg capsule taken orally once daily
Placebo AliskirenDrug
Placebo Aliskiren taken orally once daily.
Placebo AmlodipineDrug
Placebo Amlodipine taken orally once daily

Study groups in NCT00417170
Study group	Role	What they receive
Aliskiren 300 mg	Experimental	Eligible participants received oral Aliskiren 300 mg + Placebo Amlodipine once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed. Receives: Drug: Aliskiren; Drug: Placebo Amlodipine
Amlodipine 5 mg	Active comparator	Eligible participants received oral Amlodipine 5 mg + Placebo Aliskiren once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed. Receives: Drug: Amlodipine; Drug: Placebo Aliskiren

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From Baseline and After 12 Weeks of Treatment
MBF is measured by Positron Emission Tomography (PET) first at rest, then 45 minutes later, during cold pressor testing (CPT). The patient is placed in the PET scanner and injected with N-13 ammonia as a tracer. PET images are taken to assess myocardial blood flow at rest. After 40 minutes, the patient immerses one hand in ice water and PET images are taken to assess myocardial blood flow at sympathetic activation. Change from baseline data is analyzed by an analysis of variance (ANOVA) model including treatment and week as fixed factors and subject (nested in treatment) as a random factor.
Measured: At baseline and after 12 weeks of treatment

Secondary outcomes (4)

Mean Change in Insulin Sensitivity as Measured by Glucose Infusion Rate (Last 30 Minutes) From Baseline and After 12 Weeks of Treatment.
Insulin sensitivity is measured by the hyperglycemic euglycemic clamp procedure where a supine patient has 2 IV lines inserted for sampling blood. Regular human insulin (60mU/m^2 surface area/min) is infused for 120 minutes. Dextrose (20% w/v) is infused to maintain glycemia at < 100 mg/dL and is adjusted based on plasma glucose levels obtained every 5 minutes. Blood for glucose and insulin is taken at specified time intervals. Change from baseline data is analyzed by analysis of variance model including treatment and week as fixed factors, and subject (nested in treatment) as a random factor.
Measured: At baseline and after 12 weeks of treatment
Mean Change in Insulin Concentration as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of Treatment
Insulin Concentration is determined by the Oral Glucose Tolerance Test (OGTT) which begins after a 10 hour overnight fast. Blood samples are taken at baseline and after an oral 75 gram dose of glucose. Additional samples of blood are taken to measure glucose and insulin levels at 30, 60, 120 and 180 minutes post glucose intake. Changes from pre-glucose intake values are analyzed by an analysis of variance (ANOVA) model including treatment, visit and post-dose time points ( 30, 60, 120 and 180 minutes) as fixed factors and subject (nested in treatment) as a random factor.
Measured: At baseline and after 12 weeks of treatment
Mean Change From Baseline in Inflammatory Marker ( C-peptide) as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of Treatment [Time Frame: At Baseline and After 12 Weeks of Treatment
C-peptide level is determined by the Oral Glucose Tolerance Test (OGTT) which begins after a 10 hour overnight fast. Blood samples are taken at baseline and after an oral 75 gram dose of glucose. Additional samples of blood are taken to measure glucose and insulin levels at 30, 60, 120 and 180 minutes post glucose intake. Changes from pre-glucose intake values are analyzed by an analysis of variance (ANOVA) model including treatment, visit and post-dose time points ( 30, 60, 120 and 180 minutes) as fixed factors and subject (nested in treatment) as a random factor.
Measured: Baseline and after 12 weeks of treatment
Mean Change in Arterial Compliance as Measured by Pulse Wave Analysis From Baseline and After 12 Weeks of Treatment
Arterial Compliance is determined by Pulse Wave Analysis measured by a detector placed at the carotid artery while taking ECG and tonometry at the same time. Procedure is repeated for the femoral artery. Pulse Wave data are calculated by dividing distance between 2 arteries by the difference between the rise delay of the distal pulse wave and the R wave of the QRS complex and the rise delay of the proximal pulse wave to the QRS complex. Data analysis used an analysis of variance (ANOVA) model including treatment and week as fixed factors and subject (nested in treatment) as a random factor.
Measured: At baseline and after 12 weeks of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2007Jul 2010

First posted29 Dec 2006 (estimated)
Study startOct 2007
Primary completionJul 2010
Study completionJul 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.
Other trials for High Blood PressureStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00417170
Sponsor's protocol ID: CSPP100A2239
Status last verified: Sep 2011
First submitted: 28 Dec 2006
Last updated: 26 Sep 2011
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-blind, Double Dummy, Randomized Parallel Design Trial to Study the Effects of 12 Weeks of Treatment With 300mg Aliskiren vs. 5mg Amlodipine on Insulin Resistance and Endothelial Dysfunction in Hypertensive Patients With Metabolic Syndrome
ClinicalTrials.gov ID: NCT00417170
Acronym / sponsor ID: CSPP100A2239
Conditions: High Blood Pressure, Metabolic Syndrome, Insulin Resistance, Endothelial Dysfunction
Keywords: High Blood pressure, Hypertension, metabolic syndrome, insulin resistance, endothelial dysfunction, pre-diabetic, amlodipine,, aliskiren,
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Oct 2007
Primary completion: Jul 2010 (actual)
Study completion: Jul 2010 (actual)
First posted: 29 Dec 2006 (estimated)
Results: Posted 11 Aug 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Aliskiren 300 mg	Experimental	Drug: Aliskiren, Drug: Placebo AmlodipineEligible participants received oral Aliskiren 300 mg + Placebo Amlodipine once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed.
Amlodipine 5 mg	Active comparator	Drug: Amlodipine, Drug: Placebo AliskirenEligible participants received oral Amlodipine 5 mg + Placebo Aliskiren once daily for 12 weeks. Study medication was taken with 200 mL of water in the morning. Breakfast was eaten 1 hour after taking study medication. Study medication was swallowed whole, and not chewed.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Male or female adults aged 18 to 55 years, inclusive.
Sitting diastolic blood pressure ≥80 mm Hg and/or sitting systolic blood pressure ≥ 130 at screening.
Metabolic Syndrome as defined by the Adult Treatment Panel (ATP) III criteria.
Hypertension (defined above) and impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) plus one or more out of the remaining 3 criteria to satisfy entry into the study. IGT and IFG will be classified according to American Diabetes Association (ADA) guidelines:
Abnormal Positron Emission Tomography (PET) results at baseline. (Myocardial Blood Flow (MBF) of less than or equal to 35%.)

Key exclusion criteria (11 listed)

Smokers (use of tobacco products in the recent past)
Cardiovascular abnormalities including myocardial infarction, angina pectoris, hypertensive encephalopathy, stroke, transient ischemic attack, valvular heart disease, ventricular arrhythmia, A-V block, atrial fibrillation or cardiac revascularization/angioplasty in the past 12 months.
Symptoms or clinical evidence of congestive heart failure or known left ventricular ejection fraction < 40%.
Supine Blood pressure ≥ 160 mmHg systolic or ≥110 mmHg diastolic.
Clinically significant echocardiogram (ECG) abnormalities, including history of a prolonged QT-interval syndrome.

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
AliskirenAliskiren 300 mg tablets taken orally once daily	Drug	Aliskiren 300 mg
AmlodipineAmlodipine 5 mg capsule taken orally once daily	Drug	Amlodipine 5 mg
Placebo AliskirenPlacebo Aliskiren taken orally once daily.	Drug	Amlodipine 5 mg
Placebo AmlodipinePlacebo Amlodipine taken orally once daily	Drug	Aliskiren 300 mg

Primary outcome

Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From Baseline and After 12 Weeks of Treatment
Time frame: At baseline and after 12 weeks of treatment
MBF is measured by Positron Emission Tomography (PET) first at rest, then 45 minutes later, during cold pressor testing (CPT). The patient is placed in the PET scanner and injected with N-13 ammonia as a tracer. PET images are taken to assess myocardial blood flow at rest. After 40 minutes, the patient immerses one hand in ice water and PET images are taken to assess myocardial blood flow at sympathetic activation. Change from baseline data is analyzed by an analysis of variance (ANOVA) model including treatment and week as fixed factors and subject (nested in treatment) as a random factor.

4 secondary outcomes

Mean Change in Insulin Sensitivity as Measured by Glucose Infusion Rate (Last 30 Minutes) From Baseline and After 12 Weeks of Treatment.
Time frame: At baseline and after 12 weeks of treatment
Mean Change in Insulin Concentration as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of Treatment
Time frame: At baseline and after 12 weeks of treatment
Mean Change From Baseline in Inflammatory Marker ( C-peptide) as Measured During Oral Glucose Tolerance Test (OGTT) From Baseline and After 12 Weeks of Treatment [Time Frame: At Baseline and After 12 Weeks of Treatment
Time frame: Baseline and after 12 weeks of treatment
Mean Change in Arterial Compliance as Measured by Pulse Wave Analysis From Baseline and After 12 Weeks of Treatment
Time frame: At baseline and after 12 weeks of treatment

Results and safety

Results posted to the registry on 11 Aug 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aliskiren 300 mg	23	21
Amlodipine 5 mg	25	22

Primary outcome: Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From Baseline and After 12 Weeks of Treatment

Time frame: At baseline and after 12 weeks of treatment. Least squares mean (Standard Error). Unit: mL/g/min

Measure	Aliskiren 300 mg n = 21	Amlodipine 5 mg n = 23
Value	0.06 (0.39)	0.12 (0.39)

Population analysed: The Pharmacodynamic (PD) analysis set includes all participants with available PD data and no major protocol deviation with impact on PD data. Participants with observations at both baseline and endpoint were included in the analysis.

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aliskiren 300mg	0 of 23 (0%)	2 of 23 (8.7%)	Not reported
Amlodipine 5mg	0 of 25 (0%)	6 of 25 (24%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aliskiren and Amlodipine in people with High Blood Pressure and Metabolic Syndrome, run by Novartis Pharmaceuticals 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 9 inclusion and 11 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 26 Sep 2011. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Aug 2011). 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?

Mean Change in Endothelial Function as Measured by Myocardial Blood Flow (MBF) From Baseline and After 12 Weeks of Treatment (time frame: At baseline and after 12 weeks of treatment). 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 NCT00417170.

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 26 Sep 2011.