OBJECTIVES: I. Determine whether diverse mutations of the vasopressin-neurophysin II (AVP-NPII) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus by directing the production of an abnormal preprohormone. II. Determine whether the AVP-NPII gene-directed preprohormone accumulates and destroys magnocellular neurons because it cannot be folded and processed efficiently...
Date First Received: October 18, 1999
Last Updated: June 23, 2005
Verified by: National Center for Research Resources (NCRR), December 2003
Clinical Trial Phase: N/A | Start Date: December 1995
Overall Status: Completed
Brief Summary
Condition Keyword(s):
Intervention(s):
OBJECTIVES: I. Determine whether diverse mutations of the vasopressin-neurophysin II (AVP-NPII) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus by directing the production of an abnormal preprohormone. II. Determine whether the AVP-NPII gene-directed preprohormone accumulates and destroys magnocellular neurons because it cannot be folded and processed efficiently.
Study Type: Observational
Study Design: Screening
Detailed Clinical Trial Description
PROTOCOL OUTLINE: This project involves 2 clinical studies. Members of known kindreds participate in Study I; members of kindreds who have not been surveyed, genotyped, or phenotyped participate in Study II. In Study I, participants undergo clinical, hormonal, radiologic, and biochemical studies. Assessment on unrestricted fluid intake includes body weight, urine volume, osmolality, creatinine, sodium, potassium, urea, glucose, arginine-vasopressin (AVP), oxytocin, and aquaporin-II.
Participants with diabetes insipidus (DI) undergo a standard fluid deprivation test; those without DI undergo standard water load and hypertonic saline testing. Previously untreated DI patients may be given intranasal or subcutaneous desmopressin or oral chlorpropamide (adults only) for 2 or 3 days.
Magnetic resonance imaging of the pituitary-hypothalamic area is performed on all patients with and without gadolinium.
Infants and children are studied annually for the first 5 years or until they develop DI.
Affected adults are studied every 2-5 years.
Unaffected adults are re-tested only if they subsequently report de novo symptoms suggestive of DI.
In Study II, participants undergo similar genotype and phenotype testing. Kindreds demonstrating the familial neurohypophyseal diabetes insipidus phenotype and genotype are added to Study I. Kindreds found to have a different type of DI are directed into a companion protocol.
Intervention(s) in this Clinical Trial
- Drug: chlorpropamide
- Drug: desmopressin
Criteria for Participation in this Clinical Trial
- Verified or suspected familial neurohypophyseal diabetes insipidus with or without an identified mutation of the vasopressin-neurophysin II gene Affected and unaffected members of kindreds entered
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 6 Months
Maximum Age for this Clinical Trial: 70 Years
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: National Center for Research Resources (NCRR)
Overall Clinical Trial Officials and Contacts
Gary L. Robertson Study Chair Northwestern University
Related Publications
References
Hansen LK: Genetic basis of familial neurohypophyseal Diabetes Insipidus. Trends in Endocrinology and Metabolism 8(9): 363-372, 1997.
Rittig S, Robertson GL, Siggaard C, Kovacs L, Gregersen N, Nyborg J, Pedersen EB. Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus. Am J Hum Genet. 1996 Jan;58(1):107-17.
McLeod JF, Kovacs L, Gaskill MB, Rittig S, Bradley GS, Robertson GL. Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation. J Clin Endocrinol Metab. 1993 Sep;77(3):599A-599G.
Additional Information
Information obtained from ClinicalTrials.gov on July 02, 2009
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00004363
Study ID Number: NCRR-M01RR00048-0568
ClinicalTrials.gov Identifier: NCT00004363
Health Authority: United States: Federal Government
Clinical Trials Authorship and Review
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