Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus - Full Text View

Sponsors and Collaborators:	University of Colorado at Denver and Health Sciences Center Emory University University of Aarhus
Information provided by:	University of Colorado at Denver and Health Sciences Center
ClinicalTrials.gov Identifier:	NCT00478335

Purpose

The purpose of this research study is to determine if two investigational medications will be more effective in decreasing urine output than the currently available and routinely used medications in patients with congenital nephrogenic diabetes insipidus (NDI).

Condition	Intervention
Nephrogenic Diabetes Insipidus	Drug: sildenafil Drug: calcitonin Drug: hydrochlorothiazide/amiloride Drug: indomethacin Drug: Placebo for sildenafil Drug: placebo for calcitonin

MedlinePlus related topics: Diabetes Diabetes Insipidus Diabetes Medicines Urine and Urination

Drug Information available for: Indomethacin Hydrochlorothiazide Calcitonin human Calcitonin Fortical Sildenafil Sildenafil citrate Amiloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus

Further study details as provided by University of Colorado at Denver and Health Sciences Center:

Primary Outcome Measures:

Urine volume [ Time Frame: 24-hour ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Frequency of urination [ Time Frame: 24-hour ] [ Designated as safety issue: No ]
Urine osmolality [ Time Frame: 24-hour ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	May 2007
Estimated Study Completion Date:	August 2008

Arms	Assigned Interventions
1: Experimental 4-day treatment with hydrochlorothiazide/amiloride, indomethacin, calcitonin, sildenafil	Drug: sildenafil 25 mg QD or 50 mg QD x 4 days based on subject weight Drug: calcitonin one nasal spray daily for 4 days Drug: hydrochlorothiazide/amiloride 25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight Drug: indomethacin 50 mg QD or 50 mg BID x 8 days depending on subject weight
2: Placebo Comparator 4-day treatment with hydrochlorothiazide/amiloride, indomethacin, placebo for calcitonin, placebo for sildenafil	Drug: hydrochlorothiazide/amiloride 25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight Drug: indomethacin 50 mg QD or 50 mg BID x 8 days depending on subject weight Drug: Placebo for sildenafil one tablet daily for 4 days Drug: placebo for calcitonin one nasal spray daily

Show Detailed Description

Eligibility

Ages Eligible for Study:	5 Years to 25 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Known diagnosis of CNDI
Age 5 to 25 years
Normal kidney function
Post-void residual urine < 200 ml (determined by bladder ultrasound)

Exclusion Criteria:

Impaired kidney function
Known urinary retention or bladder dysfunction
High blood pressure
Other significant chronic medical disease (e.g., heart failure, liver disease, etc.)
Allergy to study drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00478335

Contacts

Contact: Melissa A Cadnapaphornchai, MD

720-777-6263

melissa.cadnapaphornchai@uchsc.edu

Locations

United States, Colorado
University of Colorado at Denver and Health Sciences Center	Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Melissa A Cadnapaphornchai, MD
Sub-Investigator: Robert W Schrier, MD
United States, Georgia
Emory University	Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Jeff Sands, MD
Sub-Investigator: Arlene Chapman, MD
Denmark
University of Aarhus	Recruiting
Aarhus, Denmark
Principal Investigator: Soren Rittig, MD
Sub-Investigator: Jorgen Frokiaer, MD
Sub-Investigator: Soren Nielsen, MD, PhD

Sponsors and Collaborators

University of Colorado at Denver and Health Sciences Center

Emory University

University of Aarhus

Investigators

Principal Investigator:

Melissa A Cadnapaphornchai, MD

University of Colorado at Denver and Health Sciences Center

More Information

Additional Information:

Nephrogenic Diabetes Insipidus Foundation This link exits the ClinicalTrials.gov site

Publications:

Bichet DG. Nephrogenic diabetes insipidus. Adv Chronic Kidney Dis. 2006 Apr;13(2):96-104. Review.

Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005 Oct;16(10):2836-46. Epub 2005 Aug 10. Review.

Schrier RW, Cadnapaphornchai MA. Renal aquaporin water channels: from molecules to human disease. Prog Biophys Mol Biol. 2003 Feb;81(2):117-31. Review.

Schrier RW, Cadnapaphornchai MA, Umenishi F. Water-losing and water-retaining states: role of water channels and vasopressin receptor antagonists. Heart Dis. 2001 May-Jun;3(3):210-4. Review.

Nielsen S, Kwon TH, Frokiaer J, Agre P. Regulation and dysregulation of aquaporins in water balance disorders. J Intern Med. 2007 Jan;261(1):53-64. Review.

Kotnik P, Nielsen J, Kwon TH, Krzisnik C, Frokiaer J, Nielsen S. Altered expression of COX-1, COX-2, and mPGES in rats with nephrogenic and central diabetes insipidus. Am J Physiol Renal Physiol. 2005 May;288(5):F1053-68. Epub 2005 Jan 11.

Nielsen S, Frokiaer J, Marples D, Kwon TH, Agre P, Knepper MA. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002 Jan;82(1):205-44. Review.

Bouley R, Pastor-Soler N, Cohen O, McLaughlin M, Breton S, Brown D. Stimulation of AQP2 membrane insertion in renal epithelial cells in vitro and in vivo by the cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra). Am J Physiol Renal Physiol. 2005 Jun;288(6):F1103-12. Epub 2005 Jan 11.

Responsible Party:	University of Colorado at Denver and Health Sciences Center ( Melissa Cadnapaphornchai )
Study ID Numbers:	06-0588
Study First Received:	May 23, 2007
Last Updated:	October 30, 2008
ClinicalTrials.gov Identifier:	NCT00478335 History of Changes
Health Authority:	United States: Food and Drug Administration; Denmark: Danish Medicines Agency

Keywords provided by University of Colorado at Denver and Health Sciences Center:

congenital nephrogenic diabetes insipidus
polyuria
urine osmolality
aquaporin-2
vasopressin V2 receptor

Study placed in the following topic categories:

Anti-Inflammatory Agents
Calcitonin
Vasodilator Agents
Diabetes Insipidus, Nephrogenic
Sodium Chloride Symporter Inhibitors
Diuretics
Bone Density Conservation Agents
Salmon calcitonin
Arginine Vasopressin
Calcitonin Gene-Related Peptide
Urologic Diseases
Indomethacin
Vasopressins
Anti-Inflammatory Agents, Non-Steroidal
Analgesics

Kidney Diseases
Metabolic Disorder
Metabolic Diseases
Pituitary Diseases
Cyclooxygenase Inhibitors
Diabetes Mellitus
Amiloride
Endocrine System Diseases
Sildenafil
Cardiovascular Agents
Antihypertensive Agents
Hydrochlorothiazide
Vasopressin-resistant Diabetes Insipidus
Phosphodiesterase Inhibitors
Analgesics, Non-Narcotic

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Calcitonin
Vasodilator Agents
Molecular Mechanisms of Pharmacological Action
Diabetes Insipidus, Nephrogenic
Physiological Effects of Drugs
Diuretics
Sodium Chloride Symporter Inhibitors
Bone Density Conservation Agents
Reproductive Control Agents
Gout Suppressants
Salmon calcitonin
Calcitonin Gene-Related Peptide
Membrane Transport Modulators
Tocolytic Agents

Urologic Diseases
Sensory System Agents
Therapeutic Uses
Indomethacin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Kidney Diseases
Metabolic Diseases
Pituitary Diseases
Cyclooxygenase Inhibitors
Diabetes Mellitus
Endocrine System Diseases
Enzyme Inhibitors
Sildenafil
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 07, 2009