We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02911792




Registration number
NCT02911792
Ethics application status
Date submitted
16/09/2016
Date registered
22/09/2016
Date last updated
11/05/2021

Titles & IDs
Public title
Effect of Farxiga on Renal Function and Size in Type 2 Diabetic Patients With Hyperfiltration
Scientific title
Effect of Farxiga on Renal Function and Size in Type 2 Diabetic Patients With Hyperfiltration
Secondary ID [1] 0 0
HSC20160262H
Universal Trial Number (UTN)
Trial acronym
Hyper
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dapagliflozin
Treatment: Drugs - Metformin
Treatment: Drugs - Glipizide 5 MG

Experimental: Dapagliflozin - Subjects will be randomized to dapagliflozin, 5 mg/day. After 2 weeks (Visit 5), dapagliflozin will be increased to 10 mg/day, Subjects who are taking Metformin at time of randomization we will add Dapagliflozin to current metformin.

Active Comparator: Metformin - Subjects who Drug naïve we will give Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).Subject who are on metformin at time of randomization we will add Glipizide 5 mg( to be increased to 10 mg at Visit 5), Subject who are on Glipizide at time of randomization we will add Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).


Treatment: Drugs: Dapagliflozin
SGLT2 inhibitor

Treatment: Drugs: Metformin
Oral diabetes medicine that helps control blood sugar levels.

Treatment: Drugs: Glipizide 5 MG
Oral diabetes medicine that helps control blood sugar levels.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
GFR (glomerular filtration rate) change after treatment with Dapagliflozin - Change from baseline in GFR after treatment with dapagliflozin for 4 months in the hyperfiltering diabetic group
Timepoint [1] 0 0
4 months
Primary outcome [2] 0 0
GFR (glomerular filtration rate) change after treatment with Metformin - Change from baseline in GFR after treatment with metformin for 4 months in the hyperfiltering diabetic group
Timepoint [2] 0 0
4 months
Primary outcome [3] 0 0
GFR (glomerular filtration rate) change after treatment with Dapagliflozin in normofiltering group - Change from baseline in GFR in the normofiltering group following 4 months of treatment with dapagliflozin
Timepoint [3] 0 0
4 months

Eligibility
Key inclusion criteria
- Newly diagnosed, drug naïve, hyperfiltering and normofiltration patients with type 2
diabetes mellitus (T2DM)

- Hyperfiltration is defined by GFR >135 ml/min•1.73m2

- Normofiltration by a GFR = 90-134 ml/min•1.73m2

- BMI = 20-45 kg/m2

- HbA1c = 7.5% to 12%

- Willingness to participate in the 16 week study protocol

- Hematocrit >34% --BP < 145/90 mmHg
Minimum age
30 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- > 300 mg/day albumin excretion

- Ingestion of medications known to interfere with the renin-angiotensin system or renal
function, including diuretic therapy

- Hospitalization for unstable angina, history of recent macrovascular
(MI/stroke/TIA/ACS) disease, coronary artery revascularization (within 2 months prior
to enrollment)

- Proliferative diabetic retinopathy

- History of cancer or major organ system disease

- New York Heart class II-IV heart failure Severe hepatic insufficiency and/or
significant abnormal liver function defined as aspartate aminotransferase (AST) and/or
alanine aminotransferase (ALT) > 3x ULN or total bilirubin > 2.0 mg/dL (34.2 µmo/L)

- Treatment with steroids, beta blockers, alpha blockers, antiobesity drugs

- Pregnant or nursing mothers

- Premenopausal females who are not practicing acceptable contraceptive methods
Participation in another trial with an investigational drug within 30 days Alcohol or
drug abuse within the preceding 6 months

- Any condition, psychiatric or medical, which in the opinion of the investigator would
interfere with the successful completion of the study

- Orthostatic hypotension (> 15/10 mmHg decrease upon standing for 3 minutes)

- Positive serologic evidence of current infectious liver disease including Hepatitis B
viral antibody IGM, Hepatitis B surface antigen, Hepatitis C virus antibody and HIV

- Volume depleted patients

- Estimated glomerular filtration rate <60 mL/min•1.73m2. Patients at risk for volume
depletion due to co-existing conditions or concomitant medications, such as loop
diuretics should have careful monitoring of their volume status

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Baker Medical Research Institute and Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Texas Health Science Center at San Antonio
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The investigators propose to treat newly diagnosed, hyperfiltering T2DM patients with or
without microalbuminuria with dapagliflozin or metformin for 4 months. The metformin-treated
group will serve as controls for improved glycemic control, since the investigators have
shown that insulin therapy to normalize A1c reduces hyperfiltration and kidney size in T1DM
patients.
Trial website
https://clinicaltrials.gov/show/NCT02911792
Trial related presentations / publications
Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ. The clinical significance of hyperfiltration in diabetes. Diabetologia. 2010 Oct;53(10):2093-104. doi: 10.1007/s00125-010-1794-9. Epub 2010 May 23. Review.
Magee GM, Bilous RW, Cardwell CR, Hunter SJ, Kee F, Fogarty DG. Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia. 2009 Apr;52(4):691-7. doi: 10.1007/s00125-009-1268-0. Epub 2009 Feb 7.
Tuttle KR, Bruton JL, Perusek MC, Lancaster JL, Kopp DT, DeFronzo RA. Effect of strict glycemic control on renal hemodynamic response to amino acids and renal enlargement in insulin-dependent diabetes mellitus. N Engl J Med. 1991 Jun 6;324(23):1626-32. Erratum in: N Engl J Med 1991 Dec 5;325(23):1666.
Stanton RC. Sodium glucose transport 2 (SGLT2) inhibition decreases glomerular hyperfiltration: is there a role for SGLT2 inhibitors in diabetic kidney disease? Circulation. 2014 Feb 4;129(5):542-4. doi: 10.1161/CIRCULATIONAHA.113.007071. Epub 2013 Dec 13.
Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev. 2011 Aug;32(4):515-31. doi: 10.1210/er.2010-0029. Epub 2011 May 23. Review.
Vallon V, Richter K, Blantz RC, Thomson S, Osswald H. Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J Am Soc Nephrol. 1999 Dec;10(12):2569-76.
Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014 Feb 4;129(5):587-97. doi: 10.1161/CIRCULATIONAHA.113.005081. Epub 2013 Dec 13.
Zatz R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986 Jun;77(6):1925-30.
Taal MW, Brenner BM. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int. 2000 May;57(5):1803-17. Review.
Anderson S, Vora JP. Current concepts of renal hemodynamics in diabetes. J Diabetes Complications. 1995 Oct-Dec;9(4):304-7. Review.
Ellis EN, Steffes MW, Goetz FC, Sutherland DE, Mauer SM. Glomerular filtration surface in type I diabetes mellitus. Kidney Int. 1986 Apr;29(4):889-94.
Schwieger J, Fine LG. Renal hypertrophy, growth factors, and nephropathy in diabetes mellitus. N Engl J Med 312:617-21, 1985
Malatiali S, Francis I, Barac-Nieto M. Phlorizin prevents glomerular hyperfiltration but not hypertrophy in diabetic rats. Exp Diabetes Res. 2008;2008:305403. doi: 10.1155/2008/305403.
Thomson SC, Rieg T, Miracle C, Mansoury H, Whaley J, Vallon V, Singh P. Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. Am J Physiol Regul Integr Comp Physiol. 2012 Jan 1;302(1):R75-83. doi: 10.1152/ajpregu.00357.2011. Epub 2011 Sep 21.
Pei F, Li BY, Zhang Z, Yu F, Li XL, Lu WD, Cai Q, Gao HQ, Shen L. Beneficial effects of phlorizin on diabetic nephropathy in diabetic db/db mice. J Diabetes Complications. 2014 Sep-Oct;28(5):596-603. doi: 10.1016/j.jdiacomp.2014.04.010. Epub 2014 Apr 24.
Bakker J, Olree M, Kaatee R, de Lange EE, Moons KG, Beutler JJ, Beek FJ. Renal volume measurements: accuracy and repeatability of US compared with that of MR imaging. Radiology. 1999 Jun;211(3):623-8.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02911792