- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00478335
Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
Study Overview
Status
Conditions
Detailed Description
The study involves the use of the investigational medications sildenafil and calcitonin. These medications have shown promise as treatment for NDI in laboratory (non-human) studies but have not been used for treatment of NDI in humans. At this time, there is no guarantee that these investigational medications will provide additional benefit to people with NDI.
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).
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Aarhus, Denmark
- University of Aarhus
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado at Denver and Health Sciences Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Active Therapy
4-day treatment with hydrochlorothiazide/amiloride, indomethacin, calcitonin, sildenafil
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25 mg quaque die (QD) or 50 mg QD x 4 days based on subject weight
Other Names:
one nasal spray daily for 4 days
Other Names:
25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight
Other Names:
50 mg QD or 50 mg BID x 8 days depending on subject weight
Other Names:
|
Placebo Comparator: Placebo Control
4-day treatment with hydrochlorothiazide/amiloride, indomethacin, placebo for calcitonin, placebo for sildenafil
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25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight
Other Names:
50 mg QD or 50 mg BID x 8 days depending on subject weight
Other Names:
one tablet daily for 4 days
one nasal spray daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
24h Urine Volume
Time Frame: 4-days
|
urine volume in mL/d
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4-days
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Melissa A Cadnapaphornchai, MD, University of Colorado, Denver
Publications and helpful links
General Publications
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Kidney Diseases
- Urologic Diseases
- Endocrine System Diseases
- Pituitary Diseases
- Diabetes Mellitus
- Diabetes Insipidus
- Diabetes Insipidus, Nephrogenic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Peripheral Nervous System Agents
- Urological Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Sodium Channel Blockers
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Reproductive Control Agents
- Phosphodiesterase Inhibitors
- Gout Suppressants
- Tocolytic Agents
- Diuretics, Potassium Sparing
- Phosphodiesterase 5 Inhibitors
- Sodium Chloride Symporter Inhibitors
- Acid Sensing Ion Channel Blockers
- Epithelial Sodium Channel Blockers
- Sildenafil Citrate
- Hydrochlorothiazide
- Indomethacin
- Amiloride
- Calcitonin
- Salmon calcitonin
- Calcitonin Gene-Related Peptide
- Katacalcin
Other Study ID Numbers
- 06-0588
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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