Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Allopurinol and Febuxostat on Urinary 2,8-Dihydroxyadenine Excretion

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02752633
Recruitment Status : Completed
First Posted : April 27, 2016
Results First Posted : December 27, 2017
Last Update Posted : December 27, 2017
Sponsor:
Collaborators:
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Landspitali University Hospital

Tracking Information
First Submitted Date  ICMJE April 20, 2016
First Posted Date  ICMJE April 27, 2016
Results First Submitted Date  ICMJE October 12, 2017
Results First Posted Date  ICMJE December 27, 2017
Last Update Posted Date December 27, 2017
Study Start Date  ICMJE May 2013
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2017)
Urinary 2,8-dihydroxyadenine Excretion [ Time Frame: 0, 14 and 28 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 22, 2016)
24 hour urine collection [ Time Frame: 24 hours ]
By 24 hour urine collection the urinary excretion of 2,8-dihydroxyadenine in patients taking the two study drugs, will be measured.
Change History Complete list of historical versions of study NCT02752633 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Allopurinol and Febuxostat on Urinary 2,8-Dihydroxyadenine Excretion
Official Title  ICMJE A Novel Assay for the Determination of Urinary 2,8-Dihydroxyadenine and Other Key Urinary Purine Metabolites: Effect of Allopurinol and Febuxostat on Urinary 2,8-Dihydroxyadenine Excretion in APRT Deficient Patients
Brief Summary This exploratory pilot study was an open-label, crossover, single-center and non-randomized clinical trial designed to compare the effect of the standardly employed doses of allopurinol (400 mg/day) and febuxostat (80 mg/day) on the urinary 2,8-dihydroxyadenine (DHA) excretion in patients with adenine phosphoribosyltransferase (APRT) deficiency.
Detailed Description

This exploratory pilot study was an open-label, crossover, single-center and non-randomized clinical trial designed to compare the effect of the standardly employed doses of allopurinol (400 mg/day) and febuxostat (80 mg/day) on the urinary DHA excretion in patients with APRT deficiency. The study was conducted between May 2013 and May 2015 as participants were enrolled at different times. The only study site was Landspitali - The National University Hospital of Iceland in Reykjavik, Iceland. The Data (Observational) Safety Monitoring Board (D/OSMB) constituted by the National Institutes of Health had oversight responsibility of the Data Safety Monitoring Plan for this clinical trial. The monitoring board reviewed accrual, patterns and frequencies of all adverse events, and protocol compliance every 6-12 months. All study subjects gave a written informed consent for their participation.

Study participants were recruited from a group of patients with confirmed APRT deficiency enrolled in the National Institutes of Health supported APRT Deficiency Registry of the Rare Kidney Stone Consortium (RKSC, http://www.rarekidneystones.org/). Confirmation of APRT deficiency was based upon the determination of known biallelic pathogenic APRT mutations or absent APRT enzyme activity. Participants were eligible for inclusion if they a) were currently receiving allopurinol therapy (the currently recommended treatment for patients with APRT deficiency); b) were willing to interrupt their allopurinol treatment for a total of 3 weeks as outlined below and c) were at least 18 years of age. There were no other exclusion criteria if the above inclusions criteria were met.

Study interventions After a 7-day washout period, all consenting subjects were prescribed 400 mg of allopurinol in a single daily dose for 14 days. After a second 7-day washout period, all subjects were prescribed 80 mg febuxostat in a single daily dose for another 14 days. Twenty-four hour and first morning urine samples were collected at the end of the first washout period, and at the end of allopurinol and febuxostat treatment periods, respectively (days 7, 21 and 42). To minimize the potential adverse effect of dietary purine intake on the results, participants were asked to keep a food record while they collected the first 24 hr urine sample and adhere to the same diet when they collected the other two 24 hr urine samples. No further measures were taken to control dietary purine intake during the study period. At the end of the study, all patients were advised to return to their regular allopurinol dosing regimens.

Measurements Urinary DHA was measured using a rapid and robust ultra high power liquid chromatography - electrospray tandem mass spectrometry (UPLC-MS/MS)), recently developed by our group. The 24-hour urinary DHA excretion (mg/24-hours) was measured and the urinary DHA-to-creatinine ratio (mg/mmol) in first morning urine samples was calculated. Urine and serum creatinine concentrations were measured with an isotope dilution mass spectrometry (IDMS) standardized laboratory method.

Outcome measures The primary trial endpoint is the 24 hr urinary DHA excretion and in patients taking the two study drugs, allopurinol (daily dose 400 mg) and febuxostat (daily dose 80 mg), evaluated at the conclusion of each 14 day drug treatment period.

Statistical Analysis Data are presented as urinary DHA excretion (mg/day) for timed collections and urinary DHA-to-creatinine ratio in first morning urine samples. Data for the whole group are presented as a median (range). Differences in the median urinary DHA excretion and the urinary DHA-to-creatinine ratio, off pharmacotherapy and on the two study drugs, febuxostat and allopurinol, were compared with a paired t-test.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adenine Phosphoribosyltransferase Deficiency
Intervention  ICMJE
  • Drug: Allopurinol
    This is a clinical trial comparing the effect of 80 mg/day of febuxostat to 400 mg/day of allopurinol on the urinary excretion of 2,8-dihydroxyadenine in patients with APRT deficiency.
    Other Names:
    • Apurin
    • ATC Code M04AA01
  • Drug: Febuxostat
    This is a clinical trial comparing the effect of 80 mg/day of febuxostat to 400 mg/day of allopurinol on the urinary excretion of 2,8-dihydroxyadenine in patients with APRT deficiency.
    Other Names:
    • Uloric
    • ATC Code M04AA03
Study Arms  ICMJE Experimental: Study subjects
Following a 7 day washout period all patients receive allopurinol (400 mg/day) as a single daily dose for 2 weeks. Following another 7 day washout period all participants receive febuxostat, 80 mg/day as a single daily dose, for 2 weeks.
Interventions:
  • Drug: Allopurinol
  • Drug: Febuxostat
Publications * Runolfsdottir HL, Palsson R, Agustsdottir IM, Indridason OS, Edvardsson VO. Kidney Disease in Adenine Phosphoribosyltransferase Deficiency. Am J Kidney Dis. 2016 Mar;67(3):431-8. doi: 10.1053/j.ajkd.2015.10.023. Epub 2015 Dec 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 22, 2017)
9
Original Actual Enrollment  ICMJE
 (submitted: April 22, 2016)
8
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All patients 18 year and older who are enrolled in the APRT Deficiency Registry of The Rare Kidney Stone Consortium.

Exclusion Criteria:

  • Patients do not want to interrupt drug (allopurinol) treatment for a total of two weeks as requested in protocol. No other exclusion criteria if inclusion criteria are met.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Iceland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02752633
Other Study ID Numbers  ICMJE RDCRN Protocol #6412
2013-000975-33 ( EudraCT Number )
U54DK083908 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Published in Eur J Intern Med. 2017 Dec 11, 2017. PMID: 29241594 DOI: 10.1016/j.ejim.2017.10.007
URL: http://www.sciencedirect.com/science/article/pii/S0953620517304156
Responsible Party Landspitali University Hospital
Study Sponsor  ICMJE Landspitali University Hospital
Collaborators  ICMJE
  • Mayo Clinic
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Vidar O Edvardsson, MD Landspitali - The National University Hospital of Iceland, Reykjavik
PRS Account Landspitali University Hospital
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP