Clinical trial NCT01918488: Increased Activity of a Renal Salt Transporter (ENaC) in Diabetic Kidney Disease
Official title: Increased Activity of the Epithelial Sodium Channel (ENaC) in Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Nephropathies
Hypertension
Keywords: Diabetic Nephropathies
Hypertension
Proteinuria
Albuminuria
Epithelial Sodium Channels
Epithelial Sodium Channel Blockers
Amiloride
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: Region of Southern Denmark
name: The Ministry of Science, Technology and Innovation, Denmark
name: Danish Heart Foundation
First posted: 2013-08-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to determine whether a diuretic drug called amiloride is capable of increasing renal salt excretion and thereby decrease blood pressure in diabetic patients with kidney disease. Our hypothesis states that amiloride is capable of reducing blood pressure in these patients and thus decrease the cardiovascular risk associated with diabetic kidney disease.


Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes
* Negative pregnancy test at inclusion and taking contraceptive medication
* One group with diabetic nephropathy and overt proteinuria
* One normoalbuminuric group without nephropathy
* Creatinine clearance \> 40 ml/min

Exclusion Criteria:

* Type 2 diabetes
* Receiving amiloride, glucocorticoids, aldosterone or spironolactone
* Clinically relevant organic or systemic disease including malignancy

Primary outcomes:
measure: 24-hour urinary sodium excretion induced by amiloride
timeFrame: Change from baseline urinary sodium excretion at 24 hours after amiloride administration
Secondary outcomes:
measure: Office blood pressure measurements
timeFrame: Change from baseline office blood pressure at day 4 of salt diet and at 24 hours after amiloride administration
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Cardiovascular and Renal Research
Study officials:
affiliation: University of Southern Denmark
name: Henrik Andersen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Jan Erik Henriksen, MD, PhD
role: STUDY_DIRECTOR
affiliation: Odense University Hospital
name: Claus Bistrup, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Southern Denmark
name: Boye L Jensen, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Svenningsen P, Bistrup C, Friis UG, Bertog M, Haerteis S, Krueger B, Stubbe J, Jensen ON, Thiesson HC, Uhrenholt TR, Jespersen B, Jensen BL, Korbmacher C, Skott O. Plasmin in nephrotic urine activates the epithelial sodium channel. J Am Soc Nephrol. 2009 Feb;20(2):299-310. doi: 10.1681/ASN.2008040364. Epub 2008 Dec 10.
citation: Svenningsen P, Uhrenholt TR, Palarasah Y, Skjodt K, Jensen BL, Skott O. Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations. Am J Physiol Regul Integr Comp Physiol. 2009 Dec;297(6):R1733-41. doi: 10.1152/ajpregu.00321.2009. Epub 2009 Sep 30.
citation: Saha C, Eckert GJ, Ambrosius WT, Chun TY, Wagner MA, Zhao Q, Pratt JH. Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension. Hypertension. 2005 Sep;46(3):481-7. doi: 10.1161/01.HYP.0000179582.42830.1d. Epub 2005 Aug 22.
citation: Buhl KB, Friis UG, Svenningsen P, Gulaveerasingam A, Ovesen P, Frederiksen-Moller B, Jespersen B, Bistrup C, Jensen BL. Urinary plasmin activates collecting duct ENaC current in preeclampsia. Hypertension. 2012 Nov;60(5):1346-51. doi: 10.1161/HYPERTENSIONAHA.112.198879. Epub 2012 Sep 17.