Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
NCT ID: NCT00478335
Last Updated: 2018-02-12
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
NA
4 participants
INTERVENTIONAL
2007-05-31
2012-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Study of Novel Types of Familial Diabetes Insipidus
NCT00004364
Study of the Pathogenesis and Pathophysiology of Familial Neurohypophyseal Diabetes Insipidus
NCT00004363
Subclassification of the Syndrome of Inappropriate ADH Secretion
NCT01341665
Study of Genotype and Phenotype Expression in Congenital Nephrogenic Diabetes Insipidus
NCT00004360
Desmopressin Melt Therapy in Nocturnal Polyuria Patients: Pharmacodynamic Study
NCT01439997
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The study is open to males, between the ages of 5 and 25 years who have been diagnosed with Nephrogenic diabetes insipidus (NDI) and who have normal kidney and bladder function. A total of 40 patients with NDI will be enrolled in the study. The study will involve two outpatient clinic visits, followed by a 9-night hospital stay, followed by a final follow-up outpatient clinic visit. All visits will take place within a 20-day time period.
At the first clinic visit, blood and urine testing for kidney and liver function and blood count will be performed. If the genetic alteration which causes your NDI has not been previously identified, blood for DNA testing will also be obtained. If a kidney and bladder ultrasound has not been performed in the past 6 months, it will be obtained. The ultrasound is to make sure that there is no problem with drainage of urine from the kidneys and bladder. Subjects will be asked to fill out food preference questionnaires to use for planning of meals for the hospital stay. Subjects will be given containers to collect two consecutive 24-hour urine samples at home. These urine collections will help determine how well the subjects routine medicines are working to control their NDI.
At the second clinic visit, subjects will bring in the two 24-hour urine samples. Blood will again be collected for further testing of kidney function. Subjects will be given containers to collect another 24-hour urine just prior to the hospital visit.
The third visit requires hospital admission and will be scheduled at the study site closest to the subjects home (The Children's Hospital, Denver, Colorado; University of Aarhus, Denmark). For the hospital visit, subjects will need to stop their usual NDI medications for 48 hours prior to the visit. Subjects will perform another 24-hour urine collection on the day prior to your hospital admission. This urine sample will be turned in to the laboratory when you are admitted to the hospital for the research study. The length of the hospital stay is 10 days/9 nights. During the stay, subjects can expect to have their weight, heart rate, and blood pressure checked three times a day. All urine will be collected. Blood testing will be performed every other day. Subjects will need to eat the meals provided at the hospital; all meals will be provided according to a low-salt diet restriction. Subjects may drink fluids as desired but they will need to avoid caffeine-containing beverages and alcohol.
On the first day of the hospital stay, testing will be performed to confirm the diagnosis of NDI. This test involves administration of the medicine dDAVP (Desmopressin) through an IV catheter (into a vein) with collection of urine every 30 minutes for 4 hours. subjects will be randomized (like the toss of a coin) to receive either the investigational medication treatment for 4 days followed by the routine medication treatment for 4 days or vice versa. When subjects receive the routine medication treatment, they will receive placebos (inactive substances like a sugar pill) in place of the investigational medicines. In this way, neither the subject nor the investigator will know whether the subjects are receiving the investigational or the routine medication treatment first. Medicines will be given twice a day during the hospital stay. On the last day of the hospital stay, subjects will be instructed to resume their normal diet and medications.
At a final outpatient clinic visit, blood testing and urinalysis will be performed.
Potential benefits of participation include a no-cost health examination, laboratory studies, and an evaluation of current management of NDI. There is no cost for participation in this research study. No pay will be given to participants in this research study.
This research study has been approved by the ethical review boards of the following institutions: Colorado Multiple Institutional Review Board (#06-0588), Emory University Institutional Review Board (#729-2005), and the University of Aarhus (#20050183). Individuals who decide to take part in this research study will need to sign a specific consent form at a participating institution as well as a release for use of personal health information (HIPAA form).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
CROSSOVER
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Active Therapy
4-day treatment with hydrochlorothiazide/amiloride, indomethacin, calcitonin, sildenafil
sildenafil
25 mg quaque die (QD) or 50 mg QD x 4 days based on subject weight
calcitonin
one nasal spray daily for 4 days
hydrochlorothiazide/amiloride
25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight
indomethacin
50 mg QD or 50 mg BID x 8 days depending on subject weight
Placebo Control
4-day treatment with hydrochlorothiazide/amiloride, indomethacin, placebo for calcitonin, placebo for sildenafil
hydrochlorothiazide/amiloride
25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight
indomethacin
50 mg QD or 50 mg BID x 8 days depending on subject weight
Placebo for sildenafil
one tablet daily for 4 days
placebo for calcitonin
one nasal spray daily
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
sildenafil
25 mg quaque die (QD) or 50 mg QD x 4 days based on subject weight
calcitonin
one nasal spray daily for 4 days
hydrochlorothiazide/amiloride
25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight
indomethacin
50 mg QD or 50 mg BID x 8 days depending on subject weight
Placebo for sildenafil
one tablet daily for 4 days
placebo for calcitonin
one nasal spray daily
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Age 5 to 25 years
* Normal kidney function
* Post-void residual urine \< 200 ml (determined by bladder ultrasound)
Exclusion Criteria
* 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
5 Years
25 Years
MALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Aarhus
OTHER
University of Colorado, Denver
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Melissa A Cadnapaphornchai, MD
Role: PRINCIPAL_INVESTIGATOR
University of Colorado, Denver
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Colorado at Denver and Health Sciences Center
Aurora, Colorado, United States
University of Aarhus
Aarhus, , Denmark
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Bichet DG. Nephrogenic diabetes insipidus. Adv Chronic Kidney Dis. 2006 Apr;13(2):96-104. doi: 10.1053/j.ackd.2006.01.006.
Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005 Oct;16(10):2836-46. doi: 10.1681/ASN.2005040371. Epub 2005 Aug 10.
Schrier RW, Cadnapaphornchai MA. Renal aquaporin water channels: from molecules to human disease. Prog Biophys Mol Biol. 2003 Feb;81(2):117-31. doi: 10.1016/s0079-6107(02)00049-4.
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. doi: 10.1097/00132580-200105000-00014.
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. doi: 10.1111/j.1365-2796.2006.01760.x.
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. doi: 10.1152/ajprenal.00114.2004. 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. doi: 10.1152/physrev.00024.2001.
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. doi: 10.1152/ajprenal.00337.2004. Epub 2005 Jan 11.
Related Links
Access external resources that provide additional context or updates about the study.
Nephrogenic Diabetes Insipidus Foundation
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
06-0588
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.