Aliskiren Effect on Aortic Plaque Progression "ALPINE"

Terminated

Phase 2/3 Results

Trial Description

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.

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).

Trial Stopped: Safety concerns with approved medication identified in an unrelated trial

Conditions

Interventions

  • Placebo Drug
    Intervention Desc: 150mg/300mg
    ARM 1: Kind: Experimental
    Label: 2
    ARM 2: Kind: Experimental
    Label: Placebo
    Description: 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)
  • Aliskiren Drug
    Other Names: Tekturna
    Intervention Desc: 150 mg/300mg
    ARM 1: Kind: Experimental
    Label: 1
    Description: Aliskiren
    ARM 2: Kind: Experimental
    Label: Aliskiren
    Description: Aliskiren will be administered for 2 weeks at 150mg/day oral pill, followed by 34 weeks oral therapy with 300mg/day

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Decrease of atherosclerotic plaque as seen of MRI 40 weeks No
Secondary Measure of percent change in plaque volume 40 weeks No
Primary Change in Normalized Total Aortic Wall Volume (TWV) Between the Trial Arms at the End of the Treatment Baseline and end of treatment ( 17 to 36 weeks) No
Secondary Change in the Percentage Wall Volume (PWV) Between Baseline and End of Treatment Baseline and end of treatment ( 17 to 36 weeks) No

Sponsors