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CompletedNCT02017171Updated Dec 4, 2020Results posted

A Multicenter Clinical Trial of Allopurinol to Prevent Kidney Function Loss in Type 1 Diabetes

A Phase 3 interventional study of Allopurinol and Placebo in Diabetic Nephropathies and Coronary Artery Disease, sponsored by Alessandro Doria. Completed at 30 sites in 3 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2020-12-04.

Sponsored by Alessandro Doria · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
530
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

Despite improvements during the past 20 years in blood glucose and blood pressure control, diabetic kidney disease remains one of the most important causes of health problems in patients with diabetes. Novel treatments to complement blood glucose and blood pressure control are urgently needed. The goal of this study is to see whether a medication called allopurinol may help prevent loss of kidney function among people with type 1 diabetes. Allopurinol has been used for many years to decrease high blood uric acid and treat gout - a disease characterized by arthritis, especially of the foot joints. There is evidence suggesting that allopurinol might also be useful in people with diabetes who have normal or moderately impaired kidney function to decrease the risk of developing advanced kidney disease in the future. To prove this beneficial effect of allopurinol, we will be conducting an international clinical trial at eight diabetes centers, enrolling approximately 480 patients with type 1 diabetes who are at increased risk of developing kidney disease. Participants will be randomly assigned to take allopurinol or placebo (inactive pill) for three years, during which they will be followed through periodical visits. To prevent any possible bias, neither the participants nor the clinical staff knows who is taking allopurinol and who is taking the placebo. Kidney function will be measured at the beginning and at the end of the treatment period to see whether patients taking allopurinol experience a slower loss of kidney function over time as compared to those taking the inactive pill. If this trial is successful, the reduction in health problems resulting from the prevention or delay of kidney function loss due to the use of allopurinol would have a major impact on the lives of type 1 diabetic patients as well as on society at large, significantly reducing the human and financial costs associated with diabetic kidney disease. Because of the emphasis on early intervention, the proposed trial, if successful, will establish a new paradigm in treatments to slow or prevent progression towards end stage kidney disease in type 1 diabetes far beyond anything achieved to date.

Read the detailed description

Despite improvements in the past 20 years in glycemic and blood pressure control and the introduction of 'renoprotective' drugs such as renin-angiotensin system blockers, the incidence of end-stage renal disease (ESRD) in type 1 diabetes (T1D) is not declining. Novel therapies to complement these interventions are urgently needed. Mounting evidence from prospective studies indicates that moderately elevated serum uric acid is a strong, independent predictor of an increased risk of chronic kidney disease and increased rates of loss of kidney function among T1D persons. To study whether uric acid lowering can reduce glomerular filtration rate (GFR) loss in T1D, we have established the PERL (Preventing Early Renal Function Loss in Diabetes) Consortium including investigators from Joslin Diabetes Center, the Universities of Minnesota, Colorado, Toronto, and Michigan, Northwestern University, Albert Einstein College of Medicine, and the Steno Diabetes Center in Denmark. With the support of NIH grant R03 DK094484, the Consortium has designed a three-year, multi-center, double-blind, placebo-controlled, randomized clinical trial with the specific aim of evaluating the efficacy of the urate-lowering drug allopurinol, as compared to placebo, in reducing kidney function loss among subjects with T1D. The trial is targeted to T1D patients with microalbuminuria or moderate macroalbuminuria or ongoing kidney function decline and serum uric acid levels ≥ 4.5 mg/dl, since these are the patients who are at very high risk of having rapid GFR decline and might benefit most from reductions in uric acid levels. Study subjects will be required to have a GFR between 40 and 99 ml/min/1.73 m2, consistent with the goal of intervening relatively early in the course of clinical DN rather than at later stages when structural changes are far advanced and a very large proportion of kidney function has already been lost. The primary endpoint of the study will be the GFR (as measured by iohexol plasma disappearance) at the end of a 2-month wash-out period after the 3-year intervention. Sample size calculations under various dropout and non-adherence scenarios suggest that 240 subjects in each treatment arm would provide at least 80% power to detect a clinically meaningful and achievable reduction in GFR decline in the allopurinol vs. the placebo group.If we demonstrate that allopurinol can halt or slow down GFR decline in T1D subjects, we will provide a safe and inexpensive intervention to prevent or delay kidney failure in T1D that can be applied at the earliest clinically detectable stages of renal injury. It is difficult to overstate how significant this finding would be, both from the perspective of public health and that of persons with diabetes.

Thirty-one of the 530 participants in this study were recruited as part of a pilot study (JDRF 17-2012-377, NCT01575379) and transferred to the main study (NCT02017171) when this was funded. Eligibility criteria for the pilot study were the same as those for the main study, with the exception of a wider estimated GFR interval at entry in the run-in period (eGFR=35-109) ml/min/1.73 m2) and the additional requirement of a measured GFR (iGFR) between 45 and 99 ml/min/1.73 m2 at the end of the run-in period. Pilot subjects joined the main study at a time point corresponding to the time elapsed from randomization in the pilot. Thus, they were exposed to the study medication for the same length of time (3 years) as participants who were directly enrolled in the main study. Outcomes measures were those of the main study, regardless of whether participants were transferred from the pilot or were directly enrolled in the main study.

02

Conditions studied

  • Diabetic Nephropathies
  • Coronary Artery Disease

Keywords

  • Kidney Diseases
  • Diabetic Nephropathies
  • Diabetes Mellitus
  • Diabetes Complications
  • Uric acid
  • Allopurinol
  • Glomerular filtration rate
  • Coronary artery disease
03

In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 530 is above the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

Alessandro Doria is the lead sponsor of 3 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male or female subjects with type 1 diabetes continuously treated with insulin within one year from diagnosis
  • Duration of T1D ≥ 8 years
  • Age 18-70 years
  • History or presence of microalbuminuria or moderate macroalbuminuria, or evidence of declining kidney function regardless of history or presence of albuminuria and/or RAS Blocker treatment. Micro- or moderate macroalbuminuria will be defined as at least two out of three consecutive urinary albumin excretion rates [AERs] or albumin creatinine ratios [ACRs] taken at any time during the two years before screening or at screening in the 30-5000 mg/24 hr (20-3333 ug/min) or 30-5000 mg/g range, respectively, if not on RASB agents, or in the 18-5000 mg/24 hr (12-3333 ug/min) or 18-5000 mg/g range, respectively, if on RASB agents). Evidence of declining kidney function will be defined as an eGFR (CKD-EPI) decline ≥3.0 ml/min/1.73 m2/year, estimated from the slope derived from all the available serum creatinine measurements (including the one at screening assessment) from the previous 3 years. If at least 3 serum creatinine measures are not available in the previous 3 years, then the slope can be derived from creatinine values from the previous 5 years.
  • Estimated GFR (eGFR) based on serum creatinine between 40 and 99.9 ml/min/1.73 m2 at screening. The upper and the lower limits should be decreased by 1 ml/min/1.73 m2 for each year over age 60 (with a lower limit of 35 ml/min/1.73m2) and by 10 ml/min/1.73 m2 for strict vegans.
  • Serum UA (UA) ≥ 4.5 mg/dl at screening

Exclusion criteria

Exclusion Criteria:

  • History of gout or xanthinuria or other indications for uric acid lowering therapy such as cancer chemotherapy.
  • Recurrent renal calculi.
  • Use of urate-lowering agents within 2 months before screening.
  • Current use of azathioprine, 6-mercaptopurine, didanosine, warfarin, tamoxifen, amoxicillin/ampicillin, or other drugs interacting with allopurinol.
  • Known allergy to xanthine-oxidase inhibitors or iodine containing substances.
  • HLA B*58:01 positivity (tested before randomization).
  • Renal transplant.
  • Non-diabetic kidney disease.
  • SBP>160 or DBP >100 mmHg at screening or SBP>150 or DBP>95 mmHg at the end of the run-in period.
  • Cancer treatment (excluding non-melanoma skin cancer treated by excision) within two years before screening.
  • History of clinically significant hepatic disease including hepatitis B or C and/or persistently elevated serum liver enzymes at screening and/or history of HBV/HCV positivity.
  • History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection.
  • Hemoglobin concentration \<11 g/dL (males), \<10 g/dL (females) at screening.
  • Platelet count \<100,000/mm3 at screening.
  • History of alcohol or drug abuse in the past 6 months.
  • Blood donation in the 3 months before screening.
  • Breastfeeding or pregnancy or unwillingness to be on contraception throughout the trial.
  • Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study.
  • Serious pre-existing medical problems other than diabetes, e.g. congestive heart failure, pulmonary insufficiency.
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
530 participants (actual)

Study arms

  • Experimental
    Allopurinol

    Oral allopurinol at a dose of 100 mg per day for 4 weeks and then at a dose ranging from 200 to 400 mg per day depending on kidney function

    Drug: Allopurinol

  • Placebo comparator
    Placebo

    Oral placebo tablets

    Drug: Placebo

Interventions

  • DrugAllopurinol
  • DrugPlacebo

    Inactive oral tablets identical in appearance to allopurinol tablets.

06

What researchers measure

Primary outcomes

  1. iGFR at the End of the Wash-out Period

    Glomerular filtration rate (GFR) at the end of the 2-month wash-out period following the 3-year treatment period, measured by the plasma disappearance of non-radioactive iohexol (iGFR) and adjusted for the iGFR at baseline.

    Time frame: End of the 2-month wash-out period following the 3-year treatment period (week 164)

Secondary outcomes

  1. eGFR at 4 Months of Treatment

    Glomerular filtration rate (GFR) at 4 months after randomization, estimated from serum creatinine and cystatin C and adjusted for the eGFR at baseline.

    Time frame: 4 months after randomization (week 16)

  2. iGFR the End of Treatment Period

    Glomerular filtration rate (GFR) at the end of the 3-year treatment period, measured by the plasma disappearance of non-radioactive iohexol (iGFR) and adjusted for the iGFR at baseline.

    Time frame: End of the 3-yr treatment period (week 156)

  3. iGFR Time Trajectory

    Glomerular filtration rate time trajectory estimated from iohexol disappearance GFR (iGFR) measurements at weeks 0, 80, 156, and 164. iGFR slopes were estimated by a linear mixed-effects model for longitudinal iGFR measures using a multiple imputation technique for missing values. Positive values denote increasing GFR over time, negative values denote declining iGFR over time.

    Time frame: Weeks 0, 80, 156, and 164 (from baseline to the end of washout period)

  4. eGFR Time Trajectory

    Glomerular filtration rate time trajectory from baseline to end of the 2-month wash-out period (week 164) estimated from quarterly serum creatinine measurements (eGFR). eGFR slopes were estimated by a linear mixed-effects model for longitudinal eGFR measures using a multiple imputation technique for missing values. Positive values denote increasing eGFR over time, negative values denote declining eGFR over time.

    Time frame: Weeks 0, 4, 16, 32, 48, 64, 80, 96, 112, 128, 156, and 164 (from baseline to the end of washout period)

  5. Serum Creatinine Doubling or End Stage Renal Disease (ESRD)

    Risk of serum creatinine doubling or end stage renal disease (ESRD) in the allopurinol arm as compared to placebo. Results are expressed as the number of participants who experienced an event in each treatment group. The risk of an event in the allopurinol group as compared to the risk in the placebo group is expressed as hazard ratio (estimated by means of proportional hazard regression).

    Time frame: Up to the end of the 2-month wash-out period following the 3-year treatment period (Week 0 to Week 164)

  6. AER at the End of the Wash-out Period

    Geometric mean of two urinary albumin excretion (AER) measurements at the end of the 2-month wash-out period following the 3-year treatment period, adjusted for the mean urinary AER at baseline. Results are expressed as least square means of the geometric means in each subject in each group.

    Time frame: End of the 2-month wash-out period following the 3-year treatment period (week 164)

  7. AER at the End of the Treatment Period

    Geometric mean of urinary albumin excretion rate (AER) during the last three months of the treatment period (Visits 15 and 16), adjusted for the mean urinary AER at baseline. Results are expressed as least square means of the geometric means in each subject in each group.

    Time frame: Last three months of treatment period (Weeks 142 and 156)

  8. Fatal or Non-fatal Cardiovascular Events

    Risk of cardiovascular events defined as the composite of CVD death (ICD-10 code I10 to I74.9), myocardial infarction, stroke (ischemic or hemorrhagic), coronary artery bypass grafting, or percutaneous coronary intervention in the allopurinol arm as compared to placebo.Results are expressed as the number of participants who experienced an event in each treatment group. The risk of an event in the allopurinol group as compared to the risk in the placebo group is expressed as hazard ratio (estimated by means of proportional hazard regression).

    Time frame: Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)

07

Results

Posted Nov 20, 2020

Participant flow

Participant flow — Overall Study
MilestoneAllopurinolPlacebo
Started267263
Completed205217
Not completed6246
Withdrew: Death104
Withdrew: Withdrawal by subject2317
Withdrew: Lost to follow-up2120
Withdrew: Eskd62
Withdrew: Miscellaneous23

Outcome measures

PrimaryiGFR at the End of the Wash-out Period

Glomerular filtration rate (GFR) at the end of the 2-month wash-out period following the 3-year treatment period, measured by the plasma disappearance of non-radioactive iohexol (iGFR) and adjusted for the iGFR at baseline.

Time frame:
End of the 2-month wash-out period following the 3-year treatment period (week 164)
Reported as:
Least squares mean · ml/min/1.73 m^2
iGFR at the End of the Wash-out Period
ml/min/1.73 m^2AllopurinolPlacebo
iGFR at the End of the Wash-out Period61.2 (58.1 to 64.2)61.2 (58.1 to 64.2)
Statistical analysis
  • Allopurinol vs Placebo · linear model for correlated errors · p = 0.999 (p value is not adjusted for multiple comparisons, a priori threshold for statistical significance: p\<0.05) · Mean difference (final values): 0.001 · 95% CI -1.9 to 1.9Treatment difference = Allopurinol-Placebo
SecondaryeGFR at 4 Months of Treatment

Glomerular filtration rate (GFR) at 4 months after randomization, estimated from serum creatinine and cystatin C and adjusted for the eGFR at baseline.

Time frame:
4 months after randomization (week 16)
Reported as:
Least squares mean · ml/min/1.73 m2
eGFR at 4 Months of Treatment
ml/min/1.73 m2AllopurinolPlacebo
eGFR at 4 Months of Treatment70.3 (67.3 to 73.3)70.0 (67.1 to 72.9)
Statistical analysis
  • Allopurinol vs Placebo · Mean difference (final values): 0.3 · 95% CI -1.6 to 2.2Treatment difference = Allopurinol - Placebo
SecondaryiGFR the End of Treatment Period

Glomerular filtration rate (GFR) at the end of the 3-year treatment period, measured by the plasma disappearance of non-radioactive iohexol (iGFR) and adjusted for the iGFR at baseline.

Time frame:
End of the 3-yr treatment period (week 156)
Reported as:
Least squares mean · ml/min/1.73 m2
iGFR the End of Treatment Period
ml/min/1.73 m2AllopurinolPlacebo
iGFR the End of Treatment Period61.3 (58.3 to 64.3)61.0 (57.9 to 64.0)
Statistical analysis
  • Allopurinol vs Placebo · Mean difference (final values): 0.3 · 95% CI -1.7 to 2.3Treatment difference = Allopurinol - Placebo
SecondaryiGFR Time Trajectory

Glomerular filtration rate time trajectory estimated from iohexol disappearance GFR (iGFR) measurements at weeks 0, 80, 156, and 164. iGFR slopes were estimated by a linear mixed-effects model for longitudinal iGFR measures using a multiple imputation technique for missing values. Positive values denote increasing GFR over time, negative values denote declining iGFR over time.

Time frame:
Weeks 0, 80, 156, and 164 (from baseline to the end of washout period)
Reported as:
Least squares mean · ml/min/1.73 m2/year
iGFR Time Trajectory
ml/min/1.73 m2/yearAllopurinolPlacebo
iGFR Time Trajectory-3.0 (-3.7 to -2.3)-2.5 (-3.1 to -1.8)
Statistical analysis
  • Allopurinol vs Placebo · Mean difference (final values): -0.6 · 95% CI -1.5 to 0.4Treatment difference = Allopurinol - Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
SecondaryeGFR Time Trajectory

Glomerular filtration rate time trajectory from baseline to end of the 2-month wash-out period (week 164) estimated from quarterly serum creatinine measurements (eGFR). eGFR slopes were estimated by a linear mixed-effects model for longitudinal eGFR measures using a multiple imputation technique for missing values. Positive values denote increasing eGFR over time, negative values denote declining eGFR over time.

Time frame:
Weeks 0, 4, 16, 32, 48, 64, 80, 96, 112, 128, 156, and 164 (from baseline to the end of washout period)
Reported as:
Least squares mean · ml/min/1.73 m2/year
eGFR Time Trajectory
ml/min/1.73 m2/yearAllopurinolPlacebo
eGFR Time Trajectory-2.4 (-2.9 to -1.8)-2.1 (-2.6 to -1.6)
Statistical analysis
  • Allopurinol vs Placebo · Mean difference (final values): -0.3 · 95% CI -1.0 to 0.5Treatment difference = Allopurinol - Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
SecondarySerum Creatinine Doubling or End Stage Renal Disease (ESRD)

Risk of serum creatinine doubling or end stage renal disease (ESRD) in the allopurinol arm as compared to placebo. Results are expressed as the number of participants who experienced an event in each treatment group. The risk of an event in the allopurinol group as compared to the risk in the placebo group is expressed as hazard ratio (estimated by means of proportional hazard regression).

Time frame:
Up to the end of the 2-month wash-out period following the 3-year treatment period (Week 0 to Week 164)
Reported as:
Count of participants · Participants
Serum Creatinine Doubling or End Stage Renal Disease (ESRD)
ParticipantsAllopurinolPlacebo
Serum Creatinine Doubling or End Stage Renal Disease (ESRD)1311
Statistical analysis
  • Allopurinol vs Placebo · Hazard ratio (hr): 1.2 · 95% CI 0.5 to 2.9Hazard ratio = Allopurinol / Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
SecondaryAER at the End of the Wash-out Period

Geometric mean of two urinary albumin excretion (AER) measurements at the end of the 2-month wash-out period following the 3-year treatment period, adjusted for the mean urinary AER at baseline. Results are expressed as least square means of the geometric means in each subject in each group.

Time frame:
End of the 2-month wash-out period following the 3-year treatment period (week 164)
Reported as:
Least squares mean · ug/min
AER at the End of the Wash-out Period
ug/minAllopurinolPlacebo
AER at the End of the Wash-out Period42.9 (24.7 to 74.4)31.7 (19.5 to 51.6)
Statistical analysis
  • Allopurinol vs Placebo · Ratio (final values): 1.4 · 95% CI 1.0 to 1.8Ratio = Allopurinol / Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.
SecondaryAER at the End of the Treatment Period

Geometric mean of urinary albumin excretion rate (AER) during the last three months of the treatment period (Visits 15 and 16), adjusted for the mean urinary AER at baseline. Results are expressed as least square means of the geometric means in each subject in each group.

Time frame:
Last three months of treatment period (Weeks 142 and 156)
Reported as:
Least squares mean · ug/min
AER at the End of the Treatment Period
ug/minAllopurinolPlacebo
AER at the End of the Treatment Period47.9 (32.5 to 70.6)37.4 (25.3 to 55.5)
Statistical analysis
  • Allopurinol vs Placebo · Ratio (final values): 1.3 · 95% CI 1.0 to 1.6
SecondaryFatal or Non-fatal Cardiovascular Events

Risk of cardiovascular events defined as the composite of CVD death (ICD-10 code I10 to I74.9), myocardial infarction, stroke (ischemic or hemorrhagic), coronary artery bypass grafting, or percutaneous coronary intervention in the allopurinol arm as compared to placebo.Results are expressed as the number of participants who experienced an event in each treatment group. The risk of an event in the allopurinol group as compared to the risk in the placebo group is expressed as hazard ratio (estimated by means of proportional hazard regression).

Time frame:
Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)
Reported as:
Count of participants · Participants
Fatal or Non-fatal Cardiovascular Events
ParticipantsAllopurinolPlacebo
Fatal or Non-fatal Cardiovascular Events159
Statistical analysis
  • Allopurinol vs Placebo · Hazard ratio (hr): 1.9 · 95% CI 0.8 to 4.5Hazard Ratio = Allopurinol / Placebo. Confidence intervals are not adjusted for multiplicity and should not be used to infer treatment effects.

Adverse events

Collected over In each participants, adverse event data were collected from randomization to two months after the end of pharmacological treatment, or until study discontinuation for participants who did not complete the study. This corresponds to up to 164 weeks for participants who completed the study.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Allopurinol10/267 (3.7%)93/267 (34.8%)121/267 (45.3%)
Placebo4/263 (1.5%)82/263 (31.2%)119/263 (45.2%)
Most frequent serious events
Showing 10 of 161
Most frequent serious events
EventAllopurinolPlacebo
Diabetic ketoacidosisMetabolism and nutrition disorders15/26713/263
HypoglycaemiaMetabolism and nutrition disorders2/2679/263
Renal failure acuteRenal and urinary disorders3/2678/263
Acute myocardial infarctionCardiac disorders7/2675/263
Abortion spontaneousPregnancy, puerperium and perinatal conditions2/841/95
OsteomyelitisInfections and infestations6/2674/263
CellulitisInfections and infestations3/2675/263
PneumoniaInfections and infestations4/2675/263
HyperglycaemiaMetabolism and nutrition disorders3/2675/263
Coronary artery diseaseCardiac disorders4/2674/263
Most frequent other events
Most frequent other events
EventAllopurinolPlacebo
RashSkin and subcutaneous tissue disorders43/26739/263
Upper respiratory tract infectionInfections and infestations31/26730/263
HypoglycaemiaMetabolism and nutrition disorders26/26729/263
BronchitisInfections and infestations10/26722/263
Urinary tract infectionInfections and infestations17/26721/263
NasopharyngitisInfections and infestations18/26720/263
Influenza like illnessGeneral disorders17/26714/263
Pain in extremityMusculoskeletal and connective tissue disorders14/26716/263
SinusitisInfections and infestations16/26713/263

Baseline characteristics

Age, Continuous
Age, Continuous(years)AllopurinolPlaceboTotal
Mean50.4 ± 11.251.8 ± 10.651.1 ± 10.9
Sex: Female, Male
Sex: Female, Male(Participants)AllopurinolPlaceboTotal
Female8495179
Male183168351
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AllopurinolPlaceboTotal
Hispanic or Latino16723
Not Hispanic or Latino250254504
Unknown or Not Reported123
Race (NIH/OMB)
Race (NIH/OMB)(Participants)AllopurinolPlaceboTotal
American Indian or Alaska Native112
Asian156
Native Hawaiian or Other Pacific Islander011
Black or African American283058
White230216446
More than one race5611
Unknown or Not Reported246
Body Mass Index
Body Mass Index(kg/m^2)AllopurinolPlaceboTotal
Mean29.5 ± 6.129.5 ± 5.929.5 ± 6.0
Glycated hemoglobin (HbA1c)
Glycated hemoglobin (HbA1c)(Percent)AllopurinolPlaceboTotal
Mean8.2 ± 1.38.2 ± 1.38.2 ± 1.3
Serum uric acid
Serum uric acid(mg/dl)AllopurinolPlaceboTotal
Mean6.1 ± 1.56.1 ± 1.56.1 ± 1.5
Estimated glomerular filtration rate (eGFR)
Estimated glomerular filtration rate (eGFR)(ml/min/1.73 m^2)AllopurinolPlaceboTotal
Mean75.4 ± 18.774.0 ± 19.474.7 ± 19.1

8 further baseline measures are reported on the registry.

08

Study locations

30 sites
  • Barbara Davis Center / University of Colorado Denver
    Aurora, Colorado 80045, United States
  • Kaiser Permanente Colorado Institute of Health Research
    Denver, Colorado 80231, United States
  • Emory University - Grady Memorial Hospital
    Atlanta, Georgia 30303, United States
  • Atlanta Diabetes Associates
    Atlanta, Georgia 30318, United States
  • Northwestern University Feinberg School of Medicine
    Chicago, Illinois 60611, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Joslin Diabetes Center
    Boston, Massachusetts 02215, United States
  • University of Massachusetts Memorial Health Care
    Worcester, Massachusetts 01655, United States
  • Brehm Center for Diabetes Research / University of Michigan
    Ann Arbor, Michigan 48105, United States
  • Henry Ford Health System
    Detroit, Michigan 48202, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Washington University
    Saint Louis, Missouri 63110, United States
  • Albert Einstein College of Medicine / Montefiore Medical Center
    Bronx, New York 10461, United States
  • Jacobi Medical Center
    Bronx, New York 10461, United States
  • Winthrop-University Hospital
    Mineola, New York 11501, United States
  • ICAHN School of Medicine at Mount Sinai
    New York, New York 10029, United States
  • Weill Cornell Medical Center
    New York, New York 10065, United States
  • SUNY Upstate Medical University
    Syracuse, New York 13210, United States
  • University of Texas Southwestern
    Dallas, Texas 75390, United States
  • Virginia Mason Medical Center
    Seattle, Washington 98101, United States
  • University of Washington
    Seattle, Washington 98105, United States
  • Providence Sacred Heart Medical Center
    Spokane, Washington 99204, United States
  • Gunderson Health System
    La Crosse, Wisconsin 54601, United States
  • University of Calgary
    Calgary, Alberta T2T 5C7, Canada
  • Alberta Diabetes Institute
    Edmonton, Alberta T6G 2E1, Canada
  • BC Diabetes
    Vancouver, British Columbia V5Y 3W2, Canada
  • LMC Diabetes and Endocrinology
    Toronto, Ontario M4G 3E8, Canada
  • Mount Sinai Hospital / University of Toronto
    Toronto, Ontario M5G 2C4, Canada
  • Toronto General Hospital
    Toronto, Ontario M5G 2N2, Canada
  • Steno Diabetes Center
    Gentofte, DK-2820, Denmark
09

References and documents

Publications

  • Ficociello LH, Rosolowsky ET, Niewczas MA, Maselli NJ, Weinberg JM, Aschengrau A, Eckfeldt JH, Stanton RC, Galecki AT, Doria A, Warram JH, Krolewski AS. High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up. Diabetes Care. 2010 Jun;33(6):1337-43. doi: 10.2337/dc10-0227. Epub 2010 Mar 23. PubMed 20332356 ↗
  • Hovind P, Rossing P, Tarnow L, Johnson RJ, Parving HH. Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study. Diabetes. 2009 Jul;58(7):1668-71. doi: 10.2337/db09-0014. Epub 2009 May 1. Erratum In: Diabetes. 2010 Oct;59(10):2695. PubMed 19411615 ↗
  • Jalal DI, Rivard CJ, Johnson RJ, Maahs DM, McFann K, Rewers M, Snell-Bergeon JK. Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant. 2010 Jun;25(6):1865-9. doi: 10.1093/ndt/gfp740. Epub 2010 Jan 11. PubMed 20064950 ↗
  • Maahs DM, Caramori L, Cherney DZ, Galecki AT, Gao C, Jalal D, Perkins BA, Pop-Busui R, Rossing P, Mauer M, Doria A; PERL Consortium. Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study. Curr Diab Rep. 2013 Aug;13(4):550-9. doi: 10.1007/s11892-013-0381-0. PubMed 23649945 ↗
  • Doria A, Galecki AT, Spino C, Pop-Busui R, Cherney DZ, Lingvay I, Parsa A, Rossing P, Sigal RJ, Afkarian M, Aronson R, Caramori ML, Crandall JP, de Boer IH, Elliott TG, Goldfine AB, Haw JS, Hirsch IB, Karger AB, Maahs DM, McGill JB, Molitch ME, Perkins BA, Polsky S, Pragnell M, Robiner WN, Rosas SE, Senior P, Tuttle KR, Umpierrez GE, Wallia A, Weinstock RS, Wu C, Mauer M; PERL Study Group. Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes. N Engl J Med. 2020 Jun 25;382(26):2493-2503. doi: 10.1056/NEJMoa1916624. PubMed 32579810 ↗

Related links

Study documents

  • Study protocol · Mar 6, 2018
  • Statistical analysis plan · Aug 3, 2019

Documents are hosted by the registry — open the source record to download them.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 4, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02017171
Lead sponsor
Alessandro Doria
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Juvenile Diabetes Research Foundation, Joslin Diabetes Center, University of Minnesota, University of Colorado, Denver, University of Michigan, University of Toronto, Northwestern University Feinberg School of Medicine, Albert Einstein College of Medicine, Steno Diabetes Center Copenhagen, Washington University School of Medicine, University of Washington, Emory University, University of Calgary, University of Alberta, University of Texas Southwestern Medical Center, BCDiabetes.Ca
Responsible party
Alessandro Doria (Investigator, Joslin Diabetes Center) — Sponsor-investigator
First posted
Dec 20, 2013
Start date
Feb 2014
Primary completion
Jul 15, 2019
Completion
Aug 31, 2019
Results posted
Nov 20, 2020
Last update
Dec 4, 2020

Study contacts

Alessandro Doria, MD, PhD, MPH
principal investigator · Joslin Diabetes Center
Michael Mauer, MD
principal investigator · University of Minnesota

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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