Clinical trial NCT03353298: Lowering Uric Acid in Live Kidney Donors
Official title: A Randomized, Double-blind, Placebo-controlled, 9-month, Parallel Group Study of Allopurinol to Reduce Left Ventricular Mass in Living Kidney Donors (AL-DON)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Transplant Donor of Left Kidney
Renal Transplant Donor of Right Kidney
Keywords: Uric acid
Left ventricular mass
Nephrectomy
Allopurinol
Magnetic resonance imaging
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: South-Eastern Norway Regional Health Authority
name: University of Oslo
First posted: 2017-11-27
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Kidney donor ≥ 6 months after donor nephrectomy
2. Donor nephrectomy undertaken in Norway
3. Male or female subject ≥ 18 years old
4. eGFR \>30 ml/min/1.73 m2
5. 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:

1. Adverse reactions to allopurinol or other xanthine oxidase inhibitors
2. Use of uric acid lowering therapy within 3 months
3. History of gout, xanthinuria or other indications for uric acid lowering therapy such as cancer chemotherapy
4. History of renal calculi
5. History of coronary heart disease
6. Heart failure with left ventricular ejection fraction \<45%
7. History of significant (i.e. non-physiological) cardiac valvular stenosis or insufficiency
8. History of clinically significant hepatic disease including hepatitis B or C and/or ALAT (SGPT) above the upper reference limit at screening.
9. History of HIV or AIDS
10. Severe systemic infections, current or within the last 6 months
11. History of malignancy other than localized basal cell carcinoma of the skin, treated or untreated, within the past 5 years.
12. Other life-threatening diseases
13. 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
14. 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.
15. 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.
16. Pregnant or nursing (lactating) women
17. Fertile women, unless they are using effective contraception during dosing of study treatment
18. Any reason why, in the opinion of the investigator, the patient should not participate.

Primary outcomes:
measure: Change in left ventricular mass
timeFrame: Nine months
Secondary outcomes:
measure: Change in blood pressure
timeFrame: Nine months
measure: Estimated insulin sensitivity, metabolic clearance rate of glucose
timeFrame: Nine months
measure: Number of antihypertensive medications
timeFrame: Nine months
measure: Doses of antihypertensive medications
timeFrame: Nine months
measure: Change in urinary albumin excretion
timeFrame: Nine months
measure: Change in estimated GFR
timeFrame: Nine months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Dag Olav Dahle, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moody WE, Ferro CJ, Edwards NC, Chue CD, Lin EL, Taylor RJ, Cockwell P, Steeds RP, Townend JN; CRIB-Donor Study Investigators. Cardiovascular Effects of Unilateral Nephrectomy in Living Kidney Donors. Hypertension. 2016 Feb;67(2):368-77. doi: 10.1161/HYPERTENSIONAHA.115.06608.
citation: Kao MP, Ang DS, Gandy SJ, Nadir MA, Houston JG, Lang CC, Struthers AD. Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol. 2011 Jul;22(7):1382-9. doi: 10.1681/ASN.2010111185. Epub 2011 Jun 30.
citation: Altmann U, Boger CA, Farkas S, Mack M, Luchner A, Hamer OW, Zeman F, Debl K, Fellner C, Jungbauer C, Banas B, Buchner S. Effects of Reduced Kidney Function Because of Living Kidney Donation on Left Ventricular Mass. Hypertension. 2017 Feb;69(2):297-303. doi: 10.1161/HYPERTENSIONAHA.116.08175. Epub 2017 Jan 3.
citation: Rekhraj S, Gandy SJ, Szwejkowski BR, Nadir MA, Noman A, Houston JG, Lang CC, George J, Struthers AD. High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease. J Am Coll Cardiol. 2013 Mar 5;61(9):926-32. doi: 10.1016/j.jacc.2012.09.066.
citation: Szwejkowski BR, Gandy SJ, Rekhraj S, Houston JG, Lang CC, Morris AD, George J, Struthers AD. Allopurinol reduces left ventricular mass in patients with type 2 diabetes and left ventricular hypertrophy. J Am Coll Cardiol. 2013 Dec 17;62(24):2284-93. doi: 10.1016/j.jacc.2013.07.074. Epub 2013 Aug 28.