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The Influence of Rosiglitazone on the Diuretic Effect of Furosemide and Amiloride

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00285805
First received: February 1, 2006
Last updated: August 23, 2010
Last verified: October 2008
History of Changes
  Purpose

Thiazolidinedione derivates (TZD's) are Peroxisome-Proliferator-Activated-Receptor-γ agonists (PPARγ-agonists) and enhance insulin sensitivity. One of the side effects, however, is the fact that subjects treated with these drugs seem to be more prone to fluid retention. The precise mechanism of rosiglitazone-related fluid retention is unknown, but it is clear that either primary or secondary renal sodium retention is part of the mechanism. Furthermore in observational studies, TZD-related oedema seems to be resistant to loop diuretic therapy. The recent finding that rosiglitazone induces upregulation of the epithelial sodium channel (ENaC) in the kidney could be the explanation for TZD-related fluid retention and the observed resistance to loop diuretics. In the present human in-vivo study the following hypothesis will be tested:

Rosiglitazone treatment stimulates the activity of ENaC in the distal nephron, which enhances the natriuretic effect of amiloride and decreases the natriuretic effect of furosemide in parallel.


Condition Intervention
Insulin Resistance
 Drug: Rosiglitazone versus placebo
Drug: response (sodium excretion) to amiloride infusion
Drug: response (sodium excretion) to furosemide infusion

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Influence of Rosiglitazone on the Diuretic Effect of Furosemide and Amiloride. A Double-blind Placebo Controlled Cross Over Study.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Difference in cumulative sodium excretion over an 8-hour period following amiloride infusion after 9 weeks of treatment with either rosiglitazone or placebo. [ Time Frame: week: 9, 22 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The difference in ER50 (urine excretion rate of furosemide with the half maximal effect) after 8 weeks of treatment with either rosiglitazone or placebo. [ Time Frame: week: 8, 21 ] [ Designated as safety issue: No ]
  • The difference in the ENac abundance in exosomes in the urine measured after 8 weeks of treatment with either rosiglitazone or placebo [ Time Frame: week: 8, 21 ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: February 2006
Study Completion Date: November 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Rosiglitazone-placebo Drug: Rosiglitazone versus placebo Drug: response (sodium excretion) to amiloride infusion Drug: response (sodium excretion) to furosemide infusion
placebo-rosiglitazone Drug: Rosiglitazone versus placebo Drug: response (sodium excretion) to amiloride infusion Drug: response (sodium excretion) to furosemide infusion

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  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy but with 2 features of the metabolic syndrome (AHA/NHLBI) (16)
  • Willing and able to provide a signed and dated written informed consent.
  • Male or female subject aged between 30 and 70 years

Exclusion Criteria:

  • Fasting glucose > 7,0 mmol/L or the use of hypoglycaemic agents. If fasting plasma glucose is between 6.1 and 7,0 mmol/L,an oral 75 g glucose test will be performed to exclude diabetes mellitus.
  • Exposure to a PPAR-g agonist during the last 4 months or a documented significant hypersensitivity to a PPAR-g agonist.
  • Participant in another study.
  • Angina or heart failure (NYHA I-IV).
  • Clinically significant liver disease (3 times the upper normal limit of ALAT, ASAT, AF, γGT or LDH)
  • Clinically significant anaemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L)
  • Creatinin clearance < 40 mL/min
  • Pregnancy, lactation
  • Alcohol or drug abuse. Liquorice
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00285805

Locations
Netherlands
Radboud University Nijmegen medical centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Paul Smits, MD, PhD Radboud University Nijmegen Medical Centre, head of department Pharmacology and Toxicology.
Principal Investigator: Cees JJ Tack, MD, PhD Radboud University Nijmegen Medical Centre, chairman of the departement of diabetology
  More Information

Publications:

Responsible Party: Paul Smits, Radboud University Nijmegen Medical Center
ClinicalTrials.gov Identifier: NCT00285805     History of Changes
Other Study ID Numbers: AR-49653-3
Study First Received: February 1, 2006
Last Updated: August 23, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Rosiglitazone
Furosemide
Amiloride
Epithelial sodium channel
Sodium excretion

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Amiloride
Diuretics
Furosemide
Rosiglitazone
Sodium Channel Blockers
 Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Hypoglycemic Agents

ClinicalTrials.gov processed this record on June 18, 2013