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Aliskiren Effect on Aortic Plaque Progression (ALPINE)

This study has been terminated.
(Safety concerns with approved medication identified in an unrelated trial)
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Sanjay Rajagopalan, The Ohio State University
ClinicalTrials.gov Identifier:
NCT01417104
First received: August 8, 2011
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

This study is being done to assess the effectiveness of short term (~9 months) Aliskiren/Placebo therapy to slow down the progression of atherosclerotic disease in thoracic and abdominal aorta. This will be checked by comparing before and after therapy magnetic resonance imaging (MRI) pictures of the aortic wall. Aliskiren is an FDA approved drug for hypertension but in this study is used for a new indication. Recent studies with animals have shown that Aliskiren therapy reduces the atherosclerotic plaque. Therefore, in this study, the investigators would like to evaluate whether the investigational drug Aliskiren, which is not FDA approved for this indication has the same beneficial effects in people with atherosclerotic disease.


Condition Intervention Phase
Atherosclerosis
Drug: Aliskiren
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Aliskiren Effect on Plaque Progression In Established Atherosclerosis Using High Resolution 3D MRI (ALPINE): A Double Blind Placebo Controlled Trial

Resource links provided by NLM:


Further study details as provided by Ohio State University:

Primary Outcome Measures:
  • Change in Normalized Total Aortic Wall Volume (TWV) Between the Trial Arms at the End of the Treatment [ Time Frame: Baseline and end of treatment ( 17 to 36 weeks) ] [ Designated as safety issue: No ]

    All patients underwent imaging using a 3T, MRI system. The MRI sequence method used for wall depiction was a 3D, fat suppressed, dark blood, turbo spin echo sequence with variable flip angles (SPACE). Following co-registration of pre and post treatment MR images, and generation of MPR sections, images were magnified, contrast adjusted and patient/exam identifier information was removed and replaced by pre-assigned code to blind images for measurements.

    An experienced observer performed manual measurements of lumen and lumen plus wall areas by delineating the inner border and the outer border of the vessel wall in each cross-section image of the aorta. Using an approach similar to intravascular atheroma volume calculations, normalized total aortic wall volume (TWV) for thoracic region, abdominal region and total aorta for each patient and each exam was generated.



Secondary Outcome Measures:
  • Change in the Percentage Wall Volume (PWV) Between Baseline and End of Treatment [ Time Frame: Baseline and end of treatment ( 17 to 36 weeks) ] [ Designated as safety issue: No ]
    Using an approach similar to intravascular atheroma volume calculations, percentage wall volume (PWV) for thoracic region, abdominal region and total aorta for each patient and each exam was generated. and a difference between baseline and end of treatment was calculated.


Other Outcome Measures:
  • Change From Baseline in Resting Diastolic Blood Pressure [ Time Frame: baseline to end of treatment ( up to 36 weeks) ] [ Designated as safety issue: No ]
    Difference between end of treatment and baseline in resting diastolic blood pressure


Enrollment: 71
Study Start Date: October 2009
Study Completion Date: January 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aliskiren
Aliskiren will be administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day
Drug: Aliskiren
150 mg/300mg
Other Name: Tekturna
Placebo Comparator: Placebo
Placebo (sugar pill) built to mimic both the 150mg Aliskiren tablet ( administered for the first 2 weeks) and the 300mg Aliskiren tablet ( administered for the rest of treatment period)
Drug: Placebo
150mg/300mg
Other Name: Sugar Pill

Detailed Description:

Treatments and Clinic Visits:

The 36-week double-blind, randomized treatment phase of the trial is preceded by 2-week single-blind placebo period to assess eligibility into the active treatment period, compliance, and to confirm the baseline blood pressure values of the enrolled subjects. If at the end of the single-blind phase, inclusion criteria will not be met, the participants will not be allowed to continue on to the trial. If they are eligible they will undergo baseline MRI studies after being randomized to either placebo or Aliskiren 150 mg, with an escalation to 300 mg at 2 weeks into treatment. This dose will be maintained for the duration of the trial. After randomization and dose escalation visits (at 2 weeks), patients will return for scheduled clinic visits at weeks 12 and 36. Assessment of routine safety measures including serum creatinine and potassium will be performed at pre-designated visits (randomization, drug escalation and end-of trial). At each study visit, after having the patient in a sitting position for 5 minutes, SBP/diastolic blood pressure will be measured 3 times in accordance with the AHA Committee Report on blood pressure determination. The patient will be then asked to stand for 2 minutes, and a single blood pressure measurement will be measured in the standing position. Evidence of left ventricular hypertrophy (LVH) will be determined using the Romhilt-Estes scoring system at baseline. Specialized measurements of plasma including insulin, glucose measures, adipokines (leptin and adiponectin) and high- sensitivity C-reactive protein (hsCRP) will be performed at randomization and 12 weeks into the trial. Central aortic blood pressure assessment will be performed at randomization and end of trial/exit visits (SphygmoCor CP, AtCor Medical, Itaska, Illinois, USA). Plasma direct renin measurements will be obtained at baseline and 12 weeks in part to assess compliance of patients with their therapy (Diasource, Belgium).

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Patients, both males and females, were eligible if they were ≥ 45 years of age, with previously documented cardiovascular disease, defined as at least one of the following: myocardial infarction (MI), cerebrovascular accident (CVA), coronary bypass surgery and/or percutaneous intervention, peripheral arterial disease (PAD), defined as ankle brachial index (ABI) <0.9 and/or prior peripheral intervention/surgery. Subjects on angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB) therapy were eligible to participate, provided no dose adjustments were made during the course of the study.

Exclusion Criteria: Contraindications to the MRI exam (pacemakers, metallic implants, severe claustrophobia); diagnosis of Type II Diabetes or use of hypoglycemic drugs; uncontrolled hypertension (>145/90 mm Hg); low density lipoprotein (LDL) of ≥ 130mg/dL; renal insufficiency defined as glomerular filtration rate (GFR) ≤ 40 ml/minute (derived by the Modified Diet in Renal Disease (MDRD) equation); initiation of new therapy with statins, ACEI/ARBs, anti-oxidants, calcium channel blockers, diuretics, β blockers; transient ischemic cerebral attack during the prior 6 months; history of allergy to renin inhibitors; unstable cardiac syndromes; symptomatic arrhythmias; history of malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized prostate cancer) and history of allergy to renin inhibitors.

  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: NCT01417104

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Sanjay Rajagopalan
Novartis
Investigators
Principal Investigator: Sanjay Rajagopalan, MD Ohio State University
  More Information

No publications provided by Ohio State University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanjay Rajagopalan, MD, The Ohio State University
ClinicalTrials.gov Identifier: NCT01417104     History of Changes
Obsolete Identifiers: NCT01123629
Other Study ID Numbers: CSPP100AUS33T
Study First Received: August 8, 2011
Results First Received: October 29, 2012
Last Updated: November 28, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University:
plaque
magnetic resonance imaging (MRI)
high blood pressure
MI
heart attack
CVA
stroke
PAD

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Arterial Occlusive Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014