Evaluation of Autosomal Recessive Polycystic Kidney Disease and Congenital Hepatic Fibrosis - Full Text View

Sponsor:	National Human Genome Research Institute (NHGRI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00068224

Purpose

This study will evaluate patients with autosomal recessive polycystic kidney disease (ARPKD) and congenital hepatic fibrosis (CHF) and other related disorders (ciliopathies). People with ARPKD develop kidney cysts and eventually kidney failure, symptoms may include hypertension (high blood pressure), poor growth, and urinary infections. CHF is a specific type of liver disease associated with ARPKD. It involves fibrosis, or scarring, of the liver, which can lead to life-threatening complications, including internal bleeding of enlarged blood vessels called varices in the esophagus (food pipe). The goal of the study is to better understand the medical complications of these disorders and identify characteristics that can help in the design of new treatments.

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Condition
Autosomal Recessive Polycystic Kidney Disease Congenital Hepatic Fibrosis Caroli's Disease Polycystic Kidney Disease Joubert Syndrome Cerebro-Oculo-Renal Syndromes COACH Syndrome Senior-Loken Syndrome Dekaban-Arima Syndrome Cogan Oculomotor Apraxia Nephronophthisis Bardet-Biedl Syndrome Alstrom Syndrome Oral-Facial-Digital Syndrome

Study Type:	Observational
Official Title:	Clinical Investigations Into the Kidney and Liver Disease in Autosomal Recessive Polycystic Kidney Disease/Congenital Hepatic Fibrosis and Other Ciliopathies

Resource links provided by NLM:

Genetics Home Reference related topics: 17q21.31 microdeletion syndrome Alström syndrome Baller-Gerold syndrome Bardet-Biedl syndrome coloboma congenital hepatic fibrosis Crouzon syndrome Friedreich ataxia Joubert syndrome Leber congenital amaurosis Lenz microphthalmia syndrome Lowe syndrome lysinuric protein intolerance Miller syndrome North American Indian childhood cirrhosis oculofaciocardiodental syndrome oral-facial-digital syndrome Peters plus syndrome polycystic kidney disease retinitis pigmentosa succinic semialdehyde dehydrogenase deficiency tetrasomy 18p Help Me Understand Genetics

MedlinePlus related topics: Coma High Blood Pressure Liver Diseases

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	300
Study Start Date:	September 2003

Detailed Description:

Human disorders caused by defects of the cilia and/or centrosome (ciliopathies) are a group of distinct syndromes with overlapping features. Human ciliopathies include polycystic kidney diseases (PKD), nephronophthisis (NP), Joubert (JS) and related cerebello-oculo-renal syndromes (CORS), Bardet-Biedl (BBS), Meckel-Gruber (MGS), Oral-Facial-Digital (OFD), and Alstrom syndromes (AS). Autosomal recessive polycystic kidney disease (ARPKD), the most common pediatric ciliopathy, is characterized by cystic degeneration of the kidneys and congenital hepatic fibrosis (CHF) of the liver. JS is characterized by a distinctive cerebellar and brainstem malformation (molar tooth sign), developmental delays, episodic hyperpnea/apnea and atypical eye movements. Other features identified in JS/CORS patients include retinal dystrophy, renal disease, CHF, ocular colobomas, occipital encephalocele, and polydactyly. BBS is characterized by retinal dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, female genitourinary malformations, and renal dysfunction. AS is characterized by retinal dystrophy, obesity, progressive sensorineural hearing impairment, dilated cardiomyopathy, the insulin resistance syndrome, developmental delay and renal and hepatic disease. OFD-I is characterized by polycystic kidney disease, facial dysmorphism, and oral, digital and brain anomalies including cerebellar agenesis with or without Dandy-Walker malformation. Although at least a subset of the patients with JS/CORS, BBS, OFD, and AS are known to have significant kidney and liver involvement, the characteristics of kidney and liver disease in these syndromes are poorly defined mostly because of the limited data available only from retrospective reports.

In this protocol, we will clinically evaluate up to 300 children and adults with ARPKD/CHF and other rare ciliopathies with special emphasis on delineating the kidney and liver involvement. We will perform mutation analysis of the related genes when needed. Routine admissions will last 4-5 days and will occur approximately every 12 to 18 months. This protocol will provide longitudinal information regarding progression of renal and hepatic disease in a large cohort of patients, and will elucidate genotype-phenotype correlations. The protocol will also allow the investigators to acquire sufficient expertise in ARPKD to design therapeutic interventions in the future.

Eligibility

Ages Eligible for Study:	6 Months to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

This protocol will enroll children and adults who carry a clinical diagnosis of ARPKD, CHF, JSRD, BBS, OFD or AS and who has either PKD/NP spectrum of changes in the kidneys or CHF/Caroli's syndrome of the liver. This might rarely include adults who are unable to give informed consent.

Among patients who have received a kidney or liver allograft, those with stable graft function and without severe transplant-related complications are eligible for enrollment. Patients and their parents/legal guardians must be willing to come to the NIH Clinical Center for admission annually.

EXCLUSION CRITERIA:

Infants under 6 months of age.

Medically fragile patients who require frequent hospitalizations due to complications of end-stage renal disease (uncontrolled hypertension, severe electrolyte imbalances) or hepatic disease (current variceal bleeding, overt encephalopathy, intractable recurrent cholangitis).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068224

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Sub-Investigator: Patient Recruitment and Public Liaison Office (PRPL) For more information at the NIH Clinical Center contact

Sponsors and Collaborators

National Human Genome Research Institute (NHGRI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Kaplan BS, Fay J, Shah V, Dillon MJ, Barratt TM. Autosomal recessive polycystic kidney disease. Pediatr Nephrol. 1989 Jan;3(1):43-9.

Capisonda R, Phan V, Traubuci J, Daneman A, Balfe JW, Guay-Woodford LM. Autosomal recessive polycystic kidney disease: outcomes from a single-center experience. Pediatr Nephrol. 2003 Feb;18(2):119-26. Epub 2003 Jan 21.

Roy S, Dillon MJ, Trompeter RS, Barratt TM. Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors. Pediatr Nephrol. 1997 Jun;11(3):302-6. Erratum in: Pediatr Nephrol 1997 Oct;11(5):664.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

O'Brien K, Font-Montgomery E, Lukose L, Bryant J, Piwnica-Worms K, Edwards H, Riney L, Garcia A, Daryanani K, Choyke P, Mohan P, Heller T, Gahl WA, Gunay-Aygun M. Congenital hepatic fibrosis and portal hypertension in autosomal dominant polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):83-9.

Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman M, Graf J, Bryant JC, Kleta R, Garcia A, Edwards H, Piwnica-Worms K, Adams D, Bernardini I, Fischer RE, Krasnewich D, Oden N, Ling A, Quezado Z, Zak C, Daryanani KT, Turkbey B, Choyke P, Guay-Woodford LM, Gahl WA. Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease. Clin J Am Soc Nephrol. 2010 Jun;5(6):972-84. Epub 2010 Apr 22.

Gunay-Aygun M, Parisi MA, Doherty D, Tuchman M, Tsilou E, Kleiner DE, Huizing M, Turkbey B, Choyke P, Guay-Woodford L, Heller T, Szymanska K, Johnson CA, Glass I, Gahl WA. MKS3-related ciliopathy with features of autosomal recessive polycystic kidney disease, nephronophthisis, and Joubert Syndrome. J Pediatr. 2009 Sep;155(3):386-92.e1. Epub 2009 Jun 21.

Responsible Party:	Meral Gunay-Aygun, M.D./National Human Genome Research Institute, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00068224 History of Changes
Other Study ID Numbers:	030264, 03-HG-0264
Study First Received:	September 10, 2003
Last Updated:	December 24, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Caroli's Syndrome
Congenital Hepatic Fibrosis
Ductal Plate Malformation
Ciliopathy
Polycystic Kidney
Polycystic Liver
Nephronophthisis
Cerebral Vermis Hypoplasia
Molar Tooth Sign

Dandy-Walker Malformation
Retinopathy
Situs Inversus
Heterotaxia
Autosomal Recessive Polycystic Kidney Disease
ARPKD
Kidney
Liver

Additional relevant MeSH terms:

Apraxias
Cysts
Liver Diseases
Fibrosis
Kidney Diseases
Polycystic Kidney Diseases
Oculocerebrorenal Syndrome
Orofaciodigital Syndromes
Polycystic Kidney, Autosomal Recessive
Caroli Disease
Liver Cirrhosis
Alstrom Syndrome
Cogan Syndrome
Coma
Optic Atrophies, Hereditary

Kidney Diseases, Cystic
Leber Congenital Amaurosis
Cerebellar Diseases
Eye Abnormalities
Bardet-Biedl Syndrome
Coloboma
Abnormalities, Multiple
Ataxia
Cholestasis
Psychomotor Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neoplasms

ClinicalTrials.gov processed this record on February 09, 2012