Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients

Study Overview
=================
Brief 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.

Official Title
-----------------
P-MR Spectroscopy Evaluation of the Effect of Short-Term Treatment With Aliskiren on Kidney β-ATP/Pi Level in Kidney Transplant Patients

Conditions
-----------------
Kidney Disease, Kidney Failure, Chronic

Intervention / Treatment
-----------------
* Drug: Aliskiren
* Drug: Placebo


Participation Criteria
=================
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 If a patient experiences such an event between Visit 1 and randomization at Visit 3, he/she should be withdrawn from the screening phase.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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aliskiren<br>Aliskiren 150 mg daily for 180 days | Drug: Aliskiren<br>* Take 1 tablet (150 mg) by mouth daily for 180 days<br>* Other names: Tekturna;|
| Placebo Comparator: Placebo<br>Placebo identical to Aliskiren drug daily for 180 days | Drug: Placebo<br>* Take 1 tablet (0 mg) daily for 180 days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Aliskiren on Kidney Metabolism | Evaluation of aliskiren on kidney metabolism by P-MR spectroscopy | 180 days (completion of treatment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Transplant, Failure, Kidney