NCT03353298

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
71

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 10, 2017

Completed
17 days until next milestone

First Posted

Study publicly available on registry

November 27, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

January 17, 2018

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 25, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 25, 2020

Completed
Last Updated

February 24, 2021

Status Verified

February 1, 2021

Enrollment Period

2.7 years

First QC Date

November 10, 2017

Last Update Submit

February 23, 2021

Conditions

Renal Transplant Donor of Left KidneyRenal Transplant Donor of Right Kidney

Keywords

Uric acidLeft ventricular massNephrectomyAllopurinolMagnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • Change in blood pressure

    Nine months

  • Estimated insulin sensitivity, metabolic clearance rate of glucose

    Nine months

  • Number of antihypertensive medications

    Nine months

  • Doses of antihypertensive medications

    Nine months

  • Change in urinary albumin excretion

    Nine months

  • +1 more secondary outcomes

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Allopurinol 300 mg

Drug: Allopurinol 300 mg

Arm B

PLACEBO COMPARATOR

Placebo Oral tablets

Drug: Placebo Oral Tablet

Interventions

Allopurinol 300 mgDRUG

Allopurinol oral tablets 300 mg given to participants once daily for 9 months

Arm A
Placebo Oral TabletDRUG

placebo oral tablets given to participants once daily for 9 months

Arm B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Oslo University Hospital

Oslo, Norway

Location

Related Publications (5)

  • 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.

    PMID: 26754643BACKGROUND

  • 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.

    PMID: 21719783BACKGROUND

  • 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.

    PMID: 28049698BACKGROUND

  • 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.

    PMID: 23449426BACKGROUND

  • 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.

    PMID: 23994420BACKGROUND

MeSH Terms

Interventions

Allopurinol

Intervention Hierarchy (Ancestors)

PurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Dag Olav Dahle, MD, PhD

    Oslo University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 10, 2017

First Posted

November 27, 2017

Study Start

January 17, 2018

Primary Completion

September 25, 2020

Study Completion

September 25, 2020

Last Updated

February 24, 2021

Record last verified: 2021-02

Data Sharing

IPD Sharing
Will not share

Locations

NO(1)