Study of the Pathogenesis and Pathophysiology of Familial Neurohypophyseal Diabetes Insipidus

Diabetes Insipidus Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004363
• Other study ID #: NCRR-M01RR00048-0568
• Secondary ID: NU-568
• Status: Completed
• Phase: N/A
• First received: October 18, 1999
• Last updated: June 23, 2005
• Start date: December 1995

Study information

• Verified date: December 2003
• Source: National Center for Research Resources (NCRR)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 70 Years

Eligibility

• 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

Study Design

Primary Purpose: Screening

Related Conditions & MeSH terms

• Diabetes Insipidus
• Diabetes Insipidus, Neurohypophyseal
• Diabetes Mellitus

Intervention

Drug:
• chlorpropamide

• desmopressin

Locations

Country	Name	City	State
United States	Northwestern University Medical School	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
National Center for Research Resources (NCRR)	Northwestern University

Country where clinical trial is conducted

United States, 

References & Publications (3)

Hansen LK, Rittig S, Robertson GL. Genetic basis of familial neurohypophyseal diabetes insipidus. Trends Endocrinol Metab. 1997 Nov;8(9):363-72. — View Citation

McLeod JF, Kovács 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. — View Citation

Rittig S, Robertson GL, Siggaard C, Kovács 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. — View Citation