Lowering Uric Acid in Live Kidney Donors

Phase 2

Completed

• Conditions: Renal Transplant Donor of Right Kidney; Renal Transplant Donor of Left Kidney
• Interventions: Drug: Placebo Oral Tablet; Drug: Allopurinol 300 mg

• Registration Number: NCT03353298
• Lead Sponsor: Oslo University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-10
• Study First Submitted QC: 2017-11-22
• Study First Posted: 2017-11-27
• Study Start: 2018-01-17
• Primary Completion: 2020-09-25
• Study Completion: 2020-09-25
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-23
• Last Update Posted: 2021-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Placebo Oral Tablet	Placebo Oral tablets
Arm A	Allopurinol 300 mg	Allopurinol 300 mg

Primary Outcome Measures

Name	Time	Method
Change in left ventricular mass	Nine months	Measured change in left ventricular mass using Cardiac MRI, comparing from baseline to 9 months of treatment With allopurinol compared to placebo.

Secondary Outcome Measures

Name	Time	Method
Change in estimated GFR	Nine months	Change from baseline to 9 months in the allopurinol group compared to placebo in estimated GFR
Change in blood pressure	Nine months	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.
Estimated insulin sensitivity, metabolic clearance rate of glucose	Nine months	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.
Number of antihypertensive medications	Nine months	Change from baseline to 9 months in the allopurinol group compared to placebo in number of antihypertensive medications
Doses of antihypertensive medications	Nine months	Change from baseline to 9 months in the allopurinol group compared to placebo in doses of antihypertensive medications
Change in urinary albumin excretion	Nine months	Change from baseline to 9 months in the allopurinol group compared to placebo in urinary albumin excretion by measuring urinary albumin/creatinine ratio.

Trial Locations

Locations (1)

Oslo University Hospital; 🇳🇴 Oslo, Norway