Study of Genotype and Phenotype Expression in Congenital Nephrogenic Diabetes Insipidus

• ClinicalTrials.gov Identifier: NCT00004360
• Recruitment Status: Completed
• First Posted: October 19, 1999
• Last Update Posted: June 24, 2005
• Sponsor: National Center for Research Resources (NCRR)
• Collaborator: Northwestern University
• Information provided by: Office of Rare Diseases (ORD)

Tracking Information

• First Submitted Date: October 18, 1999
• First Posted Date: October 19, 1999
• Last Update Posted Date: June 24, 2005
• Study Start Date: September 1995
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Genotype and Phenotype Expression in Congenital Nephrogenic Diabetes Insipidus
• Official Title: Not Provided

Brief Summary

OBJECTIVES:

I. Determine the relationship between genotype variations and clinical phenotype in patients with congenital nephrogenic diabetes insipidus.

Detailed Description

PROTOCOL OUTLINE: A detailed family history is obtained from all participants. Whenever possible, standard growth curves of affected children are obtained.

Participants then undergo clinical studies of antidiuretic function. A standard fluid deprivation-vasopressin challenge is performed with timed measurements of osmolality, electrolytes, creatinine, and vasopressin. The next day, blood pressure, plasma cyclic AMP, GMP, von Willebrand Factor, Factor VIII, and urine osmolality are measured during a water load desamino-D-arginine vasopressin (dDAVP) infusion test.

Participants with a confirmed diagnosis of congenital diabetes insipidus are then treated with chlorothiazide. Daily urine volume and osmolality are determined before and after therapy. Sodium and fluid are not restricted.

For each family, the entire vasopressin V2 gene of at least 1 affected male, and where possible at least 1 obligate carrier and 1 unaffected brother of a patient is sequenced. In addition, a detailed Xq28 haplotype analysis is done to identify the origin of de novo mutations. If no mutation is found and the disorder is not transmitted in an X-linked mode, both alleles of the gene that codes for aquaporin-II are also sequenced. DNA is collected by mail from as many kindred as possible who do not participate in the clinical studies.

• Study Type: Observational
• Study Design: Not Provided
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Not Provided
• Study Population: Not Provided
• Condition: Diabetes Insipidus, Nephrogenic
• Intervention: Drug: chlorothiazide
• Study Groups/Cohorts: Not Provided

Publications *

• Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S, et al. Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Hum Genet. 1994 Aug;55(2):278-86.
• Sadeghi H, Robertson GL, Bichet DG, Innamorati G, Birnbaumer M. Biochemical basis of partial nephrogenic diabetes insipidus phenotypes. Mol Endocrinol. 1997 Nov;11(12):1806-13.
• Robertson GL, McLeod JF, Zerbe RL, et al.: Vasopressin function in heritable forms of diabetes insipidus. In: Gross P, Richter D, Robertson GL, eds.: Vasopressin: IV International Vasopressin Conference, May 23-27, 1993, Berlin Germany. Paris: John Libbey Eurotext, 1993, pp 493-503.
• Wenkert D, Merendino JJ Jr, Shenker A, Thambi N, Robertson GL, Moses AM, Spiegel AM. Novel mutations in the V2 vasopressin receptor gene of patients with X-linked nephrogenic diabetes insipidus. Hum Mol Genet. 1994 Aug;3(8):1429-30.

Recruitment Information

• Recruitment Status: Completed
• Enrollment: Not Provided
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

PROTOCOL ENTRY CRITERIA:

• Known or suspected congenital nephrogenic diabetes insipidus
• Clinically and genetically unaffected relatives entered as controls

--Patient Characteristics--

• Age: 6 months to 70 years

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT00004360
• Other Study ID Numbers: 199/11929; NU-513
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: National Center for Research Resources (NCRR)
• Collaborators: Northwestern University

Investigators

• Study Chair: Gary L. Robertson; Northwestern University

• PRS Account: Office of Rare Diseases (ORD)
• Verification Date: December 1999