Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
Condition: Kidney Disease; Kidney Failure, Chronic
MeSH terms: Kidney Diseases; Renal Insufficiency; Kidney Failure, Chronic
Intervention: Aliskiren; Placebo
Intervention description: Take 1 tablet (150 mg) by mouth daily for 180 days; Take 1 tablet (0 mg) daily for 180 days.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Transplant; Failure; Kidney

Summary:

      The purpose of this study is to evaluate the effect of a short-term aliskiren treatment on
      kidney metabolism in patients at high risk for developing kidney dysfunction (i.e. kidney
      transplanted patients). The study is aimed at evaluating if any effect on kidney metabolism
      [using proton MR Spectroscopy(1H-MRS)] can be detected following a 6 months treatment with
      aliskiren regardless of its anti-hypertensive role. 1H-MRS can record a larger number of
      chemical species (up to 40) in the kidney, and monitor changes according to the pathologic
      state and health of the transplanted kidney.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Stable patients with end stage renal disease receiving cadaveric kidney
             transplantation will be enrolled. Patients must have at least 6 months of follow-up to
             be included in the study. Patients must have stable creatinine levels in the last 6
             months (no change>0.5 mg/dl).

          -  Patients with a systolic blood pressure of 120 or above

        Exclusion Criteria:

          -  Serum potassium > 5.0 mmol/L (at the visit directly preceding Randomization);

          -  History of any cardiovascular event (stroke, TIA, MI, unstable angina, CABG,
             percutaneous coronary intervention, hospitalization due to HF) during the 3 months
             prior to Visit 1. If a patient experiences such an event between Visit 1 and
             randomization at Visit 3, he/she should be withdrawn from the screening phase. If
             suitable, the patient can be re-screened at a later stage;

          -  Hypertension (at enrollment): any patient with msSBP ≥ 170 mmHg or msDBP ≥ 110 mmHg;

          -  Congestive heart failure NYHA class III and IV;

          -  Concomitant treatment with two (2) or more renin-angiotensin-aldosterone system
             blocking agents, e.g. ACEI, ARB or aldosterone-antagonist;

          -  Unstable serum creatinine, no patients with creatinine >2.5 mg/dl will be enrolled;

          -  Second (II) or third (III) degree heart block without a pacemaker;

          -  Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia;

          -  Clinically significant valvular heart disease;

          -  Known renal artery stenosis;

          -  Any surgical or medical condition which might significantly alter the absorption,
             distribution, metabolism, or excretion of the study drugs including, but not limited
             to, any of the following: (i) History of major gastrointestinal tract surgery such as
             gastrectomy, gastroenterostomy, or bowel resection (patients with previous bariatric
             surgery > 6 months prior to Visit 1 are allowed to participate); (ii) Any history of
             pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as
             indicated by abnormal lipase or amylase; (iii) Evidence of hepatic disease as
             determined by any one of the following: SGPT value exceeding 3 x Upper Limit of Normal
             (ULN) at Visit 1, a history of hepatic encephalopathy, a history of cirrhosis,
             esophageal varices, or a history of portocaval shunt.

          -  History of malignancy other than basal cell skin cancer within the past five years.

          -  Any concurrent life threatening condition with a life expectancy less than 2 years.

          -  History or evidence of drug or alcohol abuse within the last 12 months.

          -  Any surgical or medical condition, which in the opinion of the investigator, may place
             the patient at higher risk from his/her participation in the study, or is likely to
             prevent the patient from complying with the requirements of the study or completing
             the study.

          -  History of hypersensitivity to any of the study drugs or to medications belonging to
             the same therapeutic class as the study drugs as well as known or suspected
             contraindications to the study drugs.

          -  History of noncompliance to medical regimens or unwillingness to comply with the study
             protocol.

          -  Use of other investigational drugs at the time of enrollment, or within 30 days or 5
             half-lives of enrollment, whichever is longer

          -  Any condition that in the opinion of the investigator would jeopardize the evaluation
             of efficacy or safety.

          -  Persons directly involved in the execution of this protocol.

          -  Pregnant or nursing (lactating) women

          -  Women of Child-Bearing Potential (WOCBP) unless postmenopausal for at least one year,
             surgically sterile or using effective methods of contraception as defined by local
             Health Authorities.

          -  Treatment with Cyclosporine.

        Exclusion criteria include MR contraindications:

          -  electrical implants such as cardiac pacemakers or perfusion pumps

          -  ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial
             hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or
             steel implants

          -  ferromagnetic objects such as jewelry or metal clips in clothing

          -  pregnant volunteers

          -  pre-existing medical conditions including a likelihood of developing seizures or
             claustrophobic reactions

          -  any greater than normal potential for cardiac arrest

          -  subjects less than 18 years of age.