Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus - Full Text View

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: nephrogenic diabetes insipidus neurohypophyseal diabetes insipidus

MedlinePlus related topics: Diabetes Insipidus Urine and Urination

Drug Information available for: Indomethacin Hydrochlorothiazide Amiloride Amiloride hydrochloride Calcitonin Salmon calcitonin Sildenafil Sildenafil citrate

Genetic and Rare Diseases Information Center resources: Nephrogenic Diabetes Insipidus

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 ]


Enrollment:	4
Study Start Date:	May 2007
Study Completion Date:	October 2012
Primary Completion Date:	October 2012 (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 quaque die (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 quaque die (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 (Child, Adult)
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Known diagnosis of Congenital Nephrogenic Diabetes Insipidus (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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations


United States, Colorado
University of Colorado at Denver and Health Sciences Center
Aurora, Colorado, United States, 80045
Denmark
University of Aarhus
Aarhus, Denmark

Sponsors and Collaborators

University of Colorado, Denver

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, Frøkiaer 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, Frøkiaer 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, Frøkiaer 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, Denver
ClinicalTrials.gov Identifier:	NCT00478335 History of Changes
Other Study ID Numbers:	06-0588
Study First Received:	May 23, 2007
Last Updated:	December 19, 2012
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, Nephrogenic Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Kidney Diseases Urologic Diseases Pituitary Diseases Sildenafil Citrate Calcitonin Gene-Related Peptide Indomethacin Hydrochlorothiazide Amiloride Arginine Vasopressin	Salmon calcitonin Calcitonin Vasodilator Agents Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Urological Agents Antihypertensive Agents Diuretics Natriuretic Agents Physiological Effects of Drugs Sodium Chloride Symporter Inhibitors Membrane Transport Modulators Acid Sensing Ion Channel Blockers

ClinicalTrials.gov processed this record on September 30, 2016