Longitudinal Study of Mitochondrial Hepatopathies

NCT01148550 | Suspended DMC

• 19 other identifiers: MITOHEP Study-ChiLDReN NetworkU01DK103149U01DK103140U01DK103135U01DK084575U01DK084538U01DK084536U01DK062503U01DK062500U01DK062497U01DK062481U01DK062470U01DK062466U01DK062456U01DK062453U01DK062452U01DK062445U01DK062436U24DK062456
• Study Type: observational
• Target: 90
• Locations: 2 countries
• Sites: 16

Brief Summary

The specific aims of this study are (1) to determine the clinical phenotypes and natural history of hepatic RC and FAO disorders, (2) to determine the correlation between genotype and phenotype, (3) to determine if circulating biomarkers reflect diagnosis and predict liver disease progression and survival with the native liver, (4) to determine the clinical outcome of these disorders following liver transplantation, and (5) to develop a repository of serum, plasma, urine, tissue and DNA specimens that will be used in ancillary studies. To accomplish these aims, the ChiLDReN investigators at clinical sites (currently 9 sites) will prospectively collect defined data and specimens in a uniform fashion at fixed intervals in a relatively large number of subjects. Clinical information collected from subjects and their parents will enhance the potential for meaningful research in these disorders. A biobank of previously collected subject specimens and DNA samples will be established for use in ancillary studies to be performed in addition to this study.

Conditions

Acute Liver Failure; Mitochondrial Diseases; End Stage Liver Disease; Respiratory Chain Deficiencies, Mitochondrial; Disorder of Fatty Acid Oxidation

Keywords

neonatal acute liver failure; late-onset liver failure; cholestasis,; fatty liver,; liver dysfunction,; cirrhosis

Outcome Measures

Primary Outcomes (4)

• Listing for liver transplant

  Listing for liver transplant

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

• Liver transplantation

  Liver transplantation

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

• Involvement of other organ systems known to be associated with mitochondrial diseases

  Involvement of other organ systems known to be associated with mitochondrial diseases

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

• Death

  Death

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

Secondary Outcomes (5)

• Growth failure

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

• Worsening liver function

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

• Complications of portal hypertension

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

• Neurodevelopmental outcome

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

• Health related Quality of Life

  Measured/assessed at baseline, 6 months, Years 1 through 10, and at time of liver transplant, liver or muscle biopsy or hospitalization for critical illness if applicable

Study Arms (1)

Group 1

Mitochondrial Hepatopathy Disease Group

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

A total of 150 children and young adults with suspected or documented hepatic RC defect or FAO defect between birth and 18 years old from both genders and all races and ethnic groups that meet inclusion/exclusion criteria as defined above

You may qualify if:

• Children and young adults with suspected or documented hepatic RC defector FAO defect from birth to 18 years old (through 18 years).
• Both sexes, all races and ethnic groups.
• Participants must meet one of the following sets of criteria (A or B):
• A. Potential subjects presenting with acute or chronic liver disease or acute liver failure but who have not had a liver transplant must meet one of Clinical Criteria 1 and one of Clinical Criteria 2 listed below:
• Clinical Criteria 1 (any one of the following)
• Acute liver failure, defined as severe liver dysfunction and either 1) INR \>1.5 or prothrombin time \> 15 seconds with encephalopathy or 2) INR \> 2.0 or prothrombin time \> 20 seconds with or without encephalopathy; occurring within 8 weeks of onset of illness; with no known underlying chronic liver disease, or
• Acute liver disease defined as elevated AST or ALT \>1.25 ULN and CK \<1000u/L or conjugated bilirubin \>2.0 mg/dl and \>20% of total bilirubin, or
• Chronic liver disease defined as:
• elevated ALT or AST (\>1.25 ULN) for \> 6 months, or
• conjugated hyperbilirubinemia (conjugated \[direct\] \> 2.0 mg/dl and \> 20% of total bilirubin) for \> 6 months or
• clinical stigmata of chronic liver disease, including chronic hepatomegaly, clinical findings or complications of cirrhosis or portal hypertension, impaired liver synthetic function, intractable pruritus explainable only by liver disease or end-stage liver disease, or
• abnormal liver histology including hepatic fibrosis or cirrhosis, microvesicular steatosis, canalicular cholestasis, ballooned granular red hepatocytes (AKA oncocytes), intralobular collapse/regeneration And
• Clinical Criteria 2 (any one of the following):
• Prior history of extra-hepatic organ involvement accompanied by any one or more of the signs and symptoms associated with mitochondrial dysfunction (e.g.
• hypotonia, neuro-developmental delay, seizure disorder requiring treatment with valproic acid, nystagmus, cardiomyopathy, renal tubulopathy, bone marrow failure, myopathy, hearing loss), or

You may not qualify if:

• Inability to comply with the longitudinal follow-up described below.
• Failure of a family/patient to sign the informed consent/assent document or the HIPAA authorization form.
• Known Medium Chain Acyl CoA Dehydrogenase deficiency (MCAD).
• Other known causes of liver disease.

Sponsors & Collaborators

• Arbor Research Collaborative for Health: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Michigan: collaborator

Study Sites (16)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California at San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta - Emory University

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Texas Children's Hospital (Baylor College of Medicine)

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Links

• Childhood Liver Disease Research Network (ChiLDReN) website

MeSH Terms

Conditions

Liver Failure, Acute; Mitochondrial Diseases; End Stage Liver Disease; Cholestasis; Fatty Liver; Liver Diseases; Fibrosis

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Bile Duct Diseases; Biliary Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ronald J Sokol, MD

  University of Colorado, Denver

  STUDY CHAIR

• Ed Doo, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

• John C Magee, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Lisa Henn, PhD

  Arbor Research Collaborative for Health - Data Coordinating Center

  PRINCIPAL INVESTIGATOR

• Katrina Loh, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2010
• First Posted: June 22, 2010
• Study Start: August 18, 2010
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029
• Last Updated: October 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (15); CA (1)