Lowering Uric Acid in Live Kidney Donors

Study Overview
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Brief Summary
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Recently there was described an increase in left ventricular mass after kidney donation. It is uncertain whether this is reversible or not. Allopurinol lowers uric acid in the blood and is normally indicated for gout, but studies have showed that it also can reduce the thickness of the left ventricle of the heart in people with heart- and kidney disease. The investigators wish to give allopurinol or placebo to kidney donors based on randomization and investigate if this has the same effect on kidney donors. The investigators are assessing this by performing a cardiac MRI at baseline and after 9 months of treatment. In addition the investigators wish to see if allopurinol can have beneficial effects on blood pressure and insulin sensitivity as well.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 9-month, Parallel Group Study of Allopurinol to Reduce Left Ventricular Mass in Living Kidney Donors (AL-DON)

Conditions
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Renal Transplant Donor of Left Kidney, Renal Transplant Donor of Right Kidney

Intervention / Treatment
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* Drug: Allopurinol 300 mg
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney donor ≥ 6 months after donor nephrectomy Donor nephrectomy undertaken in Norway Male or female subject ≥ 18 years old eGFR >30 ml/min/1.73 m2 Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations. Exclusion Criteria: Adverse reactions to allopurinol or other xanthine oxidase inhibitors Use of uric acid lowering therapy within 3 months History of gout, xanthinuria or other indications for uric acid lowering therapy such as cancer chemotherapy History of renal calculi History of coronary heart disease Heart failure with left ventricular ejection fraction <45% History of significant (i.e. non-physiological) cardiac valvular stenosis or insufficiency History of clinically significant hepatic disease including hepatitis B or C and/or ALAT (SGPT) above the upper reference limit at screening. History of HIV or AIDS Severe systemic infections, current or within the last 6 months History of malignancy other than localized basal cell carcinoma of the skin, treated or untreated, within the past 5 years. Other life-threatening diseases Haemoglobin concentration < 11 g/dL(males), <10 g/dL (females); white blood cell (WBC) count < 3.5 * 10^9/L; platelet count <50 *10^9/L at screening Use of the following medications at or within 14 days before the screening visit: azathioprine, mercaptopurine, vidarabin, chlorpropamide, warfarin, tamoxifen, theophylline, amoxicillin/ampicillin, cyclophosphamide, doksorubicin, bleomycin, prokarbazin, cyclosporine, didanosine. Contraindications to MRI, including: Magnetic intracranial clips. Metal fragments in orbita. Cochlea (ear) implant. Neurostimulator. Pacemaker/ICD or remaining pacemaker electrodes. Harrington rods in thorax. Claustrophobia. Unable to lie supine. Pregnant or nursing (lactating) women Fertile women, unless they are using effective contraception during dosing of study treatment Any reason why, in the opinion of the investigator, the patient should not participate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Allopurinol 300 mg | Drug: Allopurinol 300 mg<br>* Allopurinol oral tablets 300 mg given to participants once daily for 9 months<br>|
| Placebo Comparator: Arm B<br>Placebo Oral tablets | Drug: Placebo Oral Tablet<br>* placebo oral tablets given to participants once daily for 9 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular mass | Measured change in left ventricular mass using Cardiac MRI, comparing from baseline to 9 months of treatment With allopurinol compared to placebo. | Nine months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | Change from baseline to 9 months in the allopurinol group compared to placebo in systolic and diastolic ambulatory blood pressure, systolic and diastolic Office blood pressure. | Nine months | 
| Estimated insulin sensitivity, metabolic clearance rate of glucose | Change from baseline to 9 months in the allopurinol group compared to placebo in insulin sensitivity using an orgal glucose tolerance test to measure estimated metabolic clearance rate of glucose, insulin sensitivity, firth-phase insulin release and second-phase insulin release. | Nine months | 
| Number of antihypertensive medications | Change from baseline to 9 months in the allopurinol group compared to placebo in number of antihypertensive medications | Nine months | 
| Doses of antihypertensive medications | Change from baseline to 9 months in the allopurinol group compared to placebo in doses of antihypertensive medications | Nine months | 
| Change in urinary albumin excretion | Change from baseline to 9 months in the allopurinol group compared to placebo in urinary albumin excretion by measuring urinary albumin/creatinine ratio. | Nine months | 
| Change in estimated GFR | Change from baseline to 9 months in the allopurinol group compared to placebo in estimated GFR | Nine months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uric acid, Left ventricular mass, Nephrectomy, Allopurinol, Magnetic resonance imaging