Lowering Uric Acid in Live Kidney Donors

Renal Transplant Donor of Left Kidney Clinical Trial

— AL-DON  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03353298
• Other study ID #: 2017/397 C
• Secondary ID: 2017-000666-30
• Status: Completed
• Phase: Phase 2
• Start date: January 17, 2018
• Est. completion date: September 25, 2020

Study information

• Verified date: February 2021
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: September 25, 2020
• Est. primary completion date: September 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Renal Transplant Donor of Left Kidney
• Renal Transplant Donor of Right Kidney

Intervention

Drug:
• Allopurinol 300 mg
Allopurinol oral tablets 300 mg given to participants once daily for 9 months
• Placebo Oral Tablet
placebo oral tablets given to participants once daily for 9 months

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (3)

Lead Sponsor	Collaborator
Oslo University Hospital	South-Eastern Norway Regional Health Authority, University of Oslo

Country where clinical trial is conducted

Norway, 

References & Publications (5)

Altmann U, Böger 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Number of antihypertensive medications	Change from baseline to 9 months in the allopurinol group compared to placebo in number of antihypertensive medications	Nine months
Secondary	Doses of antihypertensive medications	Change from baseline to 9 months in the allopurinol group compared to placebo in doses of antihypertensive medications	Nine months
Secondary	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
Secondary	Change in estimated GFR	Change from baseline to 9 months in the allopurinol group compared to placebo in estimated GFR	Nine months