Longitudinal Study of Mitochondrial Hepatopathies (MITOHEP)
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ClinicalTrials.gov Identifier: NCT01148550 |
Recruitment Status :
Recruiting
First Posted : June 22, 2010
Last Update Posted : April 22, 2022
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Condition or disease |
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Acute Liver Failure Mitochondrial Diseases End Stage Liver Disease Respiratory Chain Deficiencies, Mitochondrial Disorder of Fatty Acid Oxidation |
This study will be conducted as part of the NIH-supported Childhood Liver Disease Research and Education Network (ChiLDREN). ChiLDREN is investigating rare cholestatic liver diseases of childhood: alpha-1 antitrypsin deficiency (A1AT), Alagille's Syndrome (AGS), progressive familial intrahepatic cholestasis (PFIC), bile acid synthesis defects and mitochondrial hepatopathies (all previously studied by the Cholestatic Liver Disease Consortium [CLiC]); biliary atresia (previously studied by the Biliary Atresia Research Consortium [BARC]); neonatal hepatitis; and cystic fibrosis liver disease, which is studied by a new branch of ChiLDREN known as the Cystic Fibrosis Liver Disease (CFLD) Network.
In this protocol, mitochondrial hepatopathies in children and young adults will be investigated. The focus will be on respiratory chain defects (RC) and defects of fatty acid oxidation (FAO). There is little known about the full spectrum of severity and long-term natural history of mitochondrial hepatopathies. Moreover, these disorders have not been subject to prospective, rigorous clinicopathological scrutiny.
Study Type : | Observational |
Estimated Enrollment : | 67 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | Longitudinal Study of Mitochondrial Hepatopathies |
Actual Study Start Date : | August 18, 2010 |
Estimated Primary Completion Date : | May 2024 |
Estimated Study Completion Date : | May 2024 |

Group/Cohort |
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Group 1
Mitochondrial Hepatopathy Disease Group
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Group 2
Subjects with Suspected Mitochondrial Hepatopathy who do not meet the enrollment criteria for Group 1 Subjects with Suspected Mitochondrial Hepatopathy who do not meet the enrollment criteria for Group 1
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- Listing for liver transplant [ Time Frame: 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 ]Listing for liver transplant
- Liver transplantation [ Time Frame: 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
- Involvement of other organ systems known to be associated with mitochondrial diseases [ Time Frame: 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
- Death [ Time Frame: 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
- Growth failure [ Time Frame: 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 ]Growth failure (defined as weight or length Z-score for age < -2)
- Worsening liver function [ Time Frame: 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 (defined as PELD >10)
- Complications of portal hypertension [ Time Frame: 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
- Neurodevelopmental outcome [ Time Frame: 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
- Health related Quality of Life [ Time Frame: 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
Biospecimen Retention: Samples With DNA

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | up to 18 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
Subjects in Group 1 (Mitochondrial Hepatopathy group) must meet all of the following inclusion criteria:
- Children and young adults with suspected or documented hepatic RC defector FAO defect from birth to 18 years old (through 18 years).
- Both genders, 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:
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Clinical Criteria 1 (any one of the following)
- 1.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
- 2.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
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3.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 onocytes), intralobular collapse/regeneration And
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Clinical Criteria 2 (any one of the following:
- 1.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
- 2.Lactic acidosis (arterial blood or free-flowing venous blood level >2.5 mmol/L or >22.5 mg/dl at any age and increased lactate:pyruvate ratio [>25.0]) or
- 3.Hypoglycemia (blood glucose <45 mg/dl on any measurement) and hypoketonuria (<1+ for urine ketones by dipstick on urine specimen obtained within 4 hours after collecting blood with low glucose concentration), or
- 4.Abnormal acyl carnitine profile, or
- 5.Documented biochemical (enzymatic) or genetic diagnosis 3b. Potential participants who have undergone a liver transplantation because of acute liver failure or end stage liver disease due to suspected or confirmed mitochondrial hepatopathy; the transplantation may have been performed at a non-ChiLDREN medical center or at a ChiLDREN Clinical Site.
B. Potential subjects who have already had a liver transplant must meet criteria 1 and either criteria 2 or criteria 3 below:
- 1.Previous liver transplantation, AND
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2.Suspected mitochondrial liver disease, based upon meeting one or more of the following criteria:
- Had a prior history of extra-hepatic organ involvement accompanied by 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
- A prior history of lactic acidosis (arterial blood or free-flowing venous blood level >2.5 mmol/L or >22.5 mg/dl at any age and increased lactate:pyruvate ratio [>25.0]), OR
- A prior history of hypoglycemia (blood glucose <45 mg/dl on any measurement) and hypoketonuria (≤1+ for urine ketones by dipstick on urine specimen obtained within 4 hours after collecting blood with low glucose concentration), OR
- A prior history of an abnormal acyl carnitine profile, OR
- Documented biochemical (enzymatic) or genetic diagnosis of a mitochondrial disorder
- 3.A documented (confirmed) mitochondrial disorder based upon the confirmation criteria specified in protocol.
Subjects in Group 2 (Suspected Mitochondrial Hepatopathy not meeting Group 1 enrollment criteria) must meet the following inclusion criteria:
- Children and young adults with suspected hepatic RC defect or FAO defect between birth through 18 years but who do not meet clinical inclusion criteria listed above for acute or chronic liver disease or acute liver failure.
- Both genders, all races and ethnic groups.
Subjects in either Group 1 or 2 must not have any of the following exclusion criteria:
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01148550
Contact: Terese Howell, BS, CCRC | 734-369-9683 | terri.howell@arborresearch.org | |
Contact: Joanne Lord, BA,LPN,CCRC | 734-369-9965 | joanne.lord@arborresearch.org |
United States, California | |
Children's Hospital Los Angeles | Recruiting |
Los Angeles, California, United States, 90027 | |
Contact: Catherine Goodhue, CPNP 323-361-4566 cgoodhue@chla.usc.edu | |
Principal Investigator: Kasper Wang, MD | |
Sub-Investigator: Danny Thomas, MD | |
Sub-Investigator: Nisreen Soufi, MD | |
Sub-Investigator: Sonia Michail, MD | |
Sub-Investigator: Rohit Kohil, MD | |
University of California at San Francisco (UCSF) | Active, not recruiting |
San Francisco, California, United States, 94143 | |
United States, Colorado | |
Children's Hospital Colorado | Recruiting |
Aurora, Colorado, United States, 80045 | |
Contact: Matthew Steinbeiss 720-777-4800 matthew.steinbeiss@childrenscolorado.org | |
Contact: Mikala Kauma 720-777-1294 mikaela.kauma@childrenscolorado.org | |
Principal Investigator: Ronald J Sokol, MD | |
Sub-Investigator: Michael Narkewicz, MD | |
Sub-Investigator: Cara Mack, MD | |
Sub-Investigator: Shikha Sundram, MD | |
Sub-Investigator: Johan Van Hove, MD | |
Sub-Investigator: Amy Feldman, MD | |
Sub-Investigator: Dania Brigham, MD | |
United States, Georgia | |
Children's Healthcare of Atlanta - Emory University | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: Rita Tory 404-785-1467 rita.tory@choa.org | |
Contact: Jeanette McFall 404-785-0421 jeanette.mcfall@choa.org | |
Principal Investigator: Saul Karpen, MD, Ph.D | |
Sub-Investigator: Nitika Gupta, MD | |
Sub-Investigator: Miriam Vos, MD, MSPH | |
Sub-Investigator: Rene Romero, MD | |
United States, Illinois | |
Ann & Robert H. Lurie Children's Hospital | Recruiting |
Chicago, Illinois, United States, 60611 | |
Contact: Susan M. Kelly, RN, BSN 312-227-3523 skelly@luriechildrens.org | |
Contact: Mary Riordan, CCRP 312-227-4558 mriordan@luriechildrens.org | |
Principal Investigator: Estella Alonso, MD | |
Sub-Investigator: Lee Bass, MD | |
United States, Indiana | |
Riley Hospital for Children | Recruiting |
Indianapolis, Indiana, United States, 46202 | |
Contact: Ann Klipsch, RN 317-944-9605 aeye@iu.edu | |
Contact: Cindy Sawyers, BSRT 317-278-1421 clsawyer@iu.edu | |
Principal Investigator: Jean Molleston, MD | |
Sub-Investigator: Molly Bozic, MD | |
Sub-Investigator: Girish Rao, MD | |
United States, Maryland | |
Johns Hopkins School of Medicine | Completed |
Baltimore, Maryland, United States, 21287 | |
United States, Missouri | |
Washington University School of Medicine | Completed |
Saint Louis, Missouri, United States, 63110 | |
United States, New York | |
Mount Sinai Medical Center | Completed |
New York, New York, United States, 10029 | |
United States, Ohio | |
Children's Hospital Medical Center | Recruiting |
Cincinnati, Ohio, United States, 45229 | |
Contact: Julie Denlinger, RN, BSN 513-636-7818 julie.denlinger@cchmc.org | |
Sub-Investigator: Jorge Bezerra, MD | |
Sub-Investigator: Joseph Palermo, MD | |
Sub-Investigator: James Heubi, MD | |
Principal Investigator: Alexander Miethke, MD | |
United States, Pennsylvania | |
The Children's Hospital of Philadelphia | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Jessi Erlichman, MPH 215-590-2525 erlichman@email.chop.edu | |
Contact: Iraklis Petrof 267-426-8613 petrofi@email.chop.edu | |
Sub-Investigator: David Piccoli, MD | |
Sub-Investigator: Elizabeth Rand, MD | |
Principal Investigator: Kathleen Loomes, MD | |
UPMC Children's Hospital of Pittsburgh | Recruiting |
Pittsburgh, Pennsylvania, United States, 15224 | |
Contact: Kathryn Bukauskas, RN, CCRC 412-692-7703 kathryn.bukauskas@chp.edu | |
Contact: Adam Kufen, RN, CCRC 412-692-6558 adam.kufen@chp.edu | |
Principal Investigator: Robert Squires, MD | |
Sub-Investigator: James Squires, MD | |
Sub-Investigator: Patrick Mckiernan, MD | |
United States, Texas | |
Texas Children's Hospital (Baylor College of Medicine) | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Laurell Cavallo 832-822-1053 Laurel.cavallo@bcm.edu | |
Contact: Cynthia Tsai, MPH 832-822-3634 ct2@bcm.edu | |
Sub-Investigator: Benjamin Shneider, MD | |
Principal Investigator: Paula Hertel, MD | |
United States, Utah | |
University of Utah | Recruiting |
Salt Lake City, Utah, United States, 84113 | |
Contact: Ann Rutherford 801-585-9495 ann.rutherford@hsc.utah.edu | |
Contact: Tyler Hall 801-587-5670 tyler.hall@hsc.utah.edu | |
Principal Investigator: Stephen Guthery, MD | |
Sub-Investigator: Kyle Jensen, MD | |
Sub-Investigator: Linda Book, MD | |
United States, Washington | |
Seattle Children's Hospital | Recruiting |
Seattle, Washington, United States, 98105 | |
Contact: Melissa Young 206-987-1037 melissa.young@seattlechildrens.org | |
Contact: Kara Cooper 206-987-4636 kara.cooper@seattlechildrens.org | |
Principal Investigator: Simon Horslen, MD | |
Sub-Investigator: Evelyn Hsu, MD | |
Sub-Investigator: Niviann Blondet, MD | |
Canada, Ontario | |
Hospital for Sick Children | Recruiting |
Toronto, Ontario, Canada, M5G 1X8 | |
Contact: Deepika Sharma 416-813-7654 ext 201594 deepika.sharma@sickkids.ca | |
Contact: Claudia Quammie 416-813-7654 ext 201594 claudia.quammie@sickkids.ca | |
Sub-Investigator: Vicky Ng, MD | |
Principal Investigator: Binita Kamath, MD |
Study Chair: | Ronald J Sokol, MD | University of Colorado, Denver | |
Study Director: | Ed Doo, MD | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | |
Principal Investigator: | John C Magee, MD | University of Michigan | |
Principal Investigator: | Robert M Merion, MD | Arbor Research Collaborative for Health - Data Coordinating Center | |
Study Director: | Averell Sherker, MD | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
neonatal acute liver failure late-onset liver failure cholestasis, |
fatty liver, liver dysfunction, cirrhosis |
Liver Diseases Liver Failure Hepatic Insufficiency End Stage Liver Disease |
Liver Failure, Acute Mitochondrial Diseases Digestive System Diseases Metabolic Diseases |