Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus - Full Text View

Sponsor:	University of Colorado, Denver
Collaborators:	Emory University University of Aarhus
Information provided by:	University of Colorado, Denver
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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus nephrogenic diabetes insipidus neurohypophyseal diabetes insipidus

MedlinePlus related topics: Diabetes Insipidus Urine and Urination

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

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

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:	October 2010
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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 Other Name: Viagra Drug: calcitonin one nasal spray daily for 4 days Other Name: Miacalcic Drug: hydrochlorothiazide/amiloride 25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight Other Name: Moduret, Moduretic Drug: indomethacin 50 mg QD or 50 mg BID x 8 days depending on subject weight Other Name: Indocin
Placebo Comparator: 2 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 Other Name: Moduret, Moduretic Drug: indomethacin 50 mg QD or 50 mg BID x 8 days depending on subject weight Other Name: Indocin Drug: Placebo for sildenafil one tablet daily for 4 days Drug: placebo for calcitonin one nasal spray daily

Arms

Assigned Interventions

Experimental: 1

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

Other Name: Viagra

Drug: calcitonin

one nasal spray daily for 4 days

Other Name: Miacalcic

Drug: hydrochlorothiazide/amiloride

25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight

Other Name: Moduret, Moduretic

Drug: indomethacin

50 mg QD or 50 mg BID x 8 days depending on subject weight

Other Name: Indocin

Placebo Comparator: 2

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

Other Name: Moduret, Moduretic

Drug: indomethacin

50 mg QD or 50 mg BID x 8 days depending on subject weight

Other Name: Indocin

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@ucdenver.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

Sponsors and Collaborators

University of Colorado, Denver

Emory University

University of Aarhus

Investigators

Principal Investigator:

Melissa A Cadnapaphornchai, MD

University of Colorado, Denver

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:	Melissa Cadnapaphornchai, University of Colorado at Denver and Health Sciences Center
ClinicalTrials.gov Identifier:	NCT00478335 History of Changes
Other Study ID Numbers:	06-0588
Study First Received:	May 23, 2007
Last Updated:	October 22, 2009
Health Authority:	United States: Food and Drug Administration; Denmark: Danish Medicines Agency

Keywords provided by University of Colorado, Denver:

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

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Insipidus
Diabetes Insipidus, Neurogenic
Diabetes Insipidus, Nephrogenic
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Kidney Diseases
Urologic Diseases
Pituitary Diseases
Amiloride
Hydrochlorothiazide
Calcitonin Gene-Related Peptide
Arginine Vasopressin
Indomethacin

Sildenafil
Salmon calcitonin
Calcitonin
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Bone Density Conservation Agents
Vasodilator Agents
Hemostatics

ClinicalTrials.gov processed this record on February 09, 2012