Liver DiseasesLOGICNCT00571272
Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC)
An observational study of Liver Diseases and Alagille Syndrome, run by Arbor Research Collaborative for Health at 17 sites in 2 countries.
Trial summary
Cholestasis is a condition in which bile is not properly transported from the liver to the small intestine. Cholestasis can be caused by an array of childhood diseases, including the genetic diseases Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis and metabolism defects, and… Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Liver Diseases, Alagille Syndrome, Alpha 1-Antitrypsin Deficiency
- How many people
- 1,675 participants
- Where
- 17 sitesin 2 countries
- Study dates
- 30 Nov 2007to 31 May 2029
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: The study population will consist of 400 participants with Alagille syndrome, 400 with alpha-1 trypsin deficieny (of which up to 25 may be siblings of participants), 300 with PFIC (or BRIC), and 50 with bile acid synthesis defects.
Who may be able to join
- Children and young adults diagnosed with one of the four cholestatic diseases from birth through 25 years old.
- Siblings of participants with alpha-1-antitrypsin deficiency, who are affected with alpha-1-antitrypsin deficiency, but have no evidence of liver disease.
- Both sexes, all races and ethnic groups.
- Participant meets the enrollment criteria for one of the four cholestatic liver diseases.
- Patient and/or parent/legal guardian have the ability to provide written informed consent for enrollment.
Who cannot join
- 1. Inability to comply with the longitudinal follow-up described in the protocol.
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States16 sites
Children's Healthcare of Atlanta - Emory University
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins University Hospital
Baltimore, Maryland, 21287
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati's Children's Memorial Hospital
Cincinnati, Ohio, 60190
Baylor School of Medicine
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Mount Sinai School of Medicine
New York, New York, 10029
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of Utah
Salt Lake City, Utah, 84113
University of California at San Francisco (UCSF)
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
St. Louis University - Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Washington University School of Medicine/St. Louis Children's Hospital
St Louis, Missouri, 63110
About this study
Cholestasis is a condition in which bile is not properly transported from the liver to the small intestine. Cholestasis can be caused by an array of childhood diseases, including the genetic diseases Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis and metabolism defects, and progressive familial intrahepatic cholestasis (PFIC) or benign recurrent intrahepatic cholestasis(BRIC). This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.
Read the detailed description
Cholestasis is a rare condition that involves a reduction or obstruction of bile flow from the liver to the small intestine. When bile flow is hindered, a waste product pigment called bilirubin can escape into the bloodstream and build up to harmful levels. This may lead to the easily recognizable cholestatic symptoms of jaundice, itching, and impaired growth and eventually to more serious health problems. Four rare genetic liver disorders- ALGS, a-1AT, bile acid synthesis and metabolism defects, and PFIC-account for about 20% to 30% of all infant cases of cholestasis. These four disorders compose a group of related diseases that can cause significant growth problems during childhood, serious liver problems, the need for liver transplantation, and potentially death. More research on these rare liver diseases is necessary to develop a scientific basis for improvement in diagnostic techniques and treatments. Current diagnostic procedures are complex, and the development of simpler diagnostic tests would facilitate early diagnosis and treatment. This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.
Participants who have been previously enrolled into this study will be followed for 20 years, until transplanted, or death. Study visits will involve review of clinical information, family history, and any clinically indicated treatments and their outcomes; a physical exam; laboratory tests; and radiologic and imaging evaluations.
- Keywords
- Cholestatic Liver Disease, Cholestasis, Childhood Diseases, Genetic Diseases, Bile Acid Synthesis and Metabolism Defects, Progressive Familial Intrahepatic Cholestasis
- Medical subject headings
- Liver Diseases, Alagille Syndrome, alpha 1-Antitrypsin Deficiency, Cholestasis, Genetic Diseases, Inborn, Cholestasis, progressive familial intrahepatic 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Infants less than 6 months old with a cholestatic liver disease who were initially enrolled into the Childhood Liver Disease Research and Education Network (ChiLDREN) Prospective Biliary Atresia Epidemiology study (PROBE study; P003) | |
| 2 | Participants with a cholestatic liver disease who are between birth and 25 years old who were NOT initially enrolled into the Childhood Liver Disease Research and Education Network (ChiLDREN) Prospective Biliary Atresia Epidemiology study (PROBE study; P003) | |
| 3 | Post-liver transplant participants with a cholestatic liver disease who are between 1 day and 25 years old. Affected parents of patients enrolled in the study are eligible for enrollment if they are 25 years old or less | |
| 5 | Affected siblings (without evidence of liver disease) of Alpha-1 Antitrypsin Deficiency participants who are enrolled in LOGIC. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Demonstration of disease progression for each of the four cholestatic liver diseases of the study, including liver transplantation, death, growth failure, worsening liver function, and developmental complications of portal high blood pressure
Measured: Measured at baseline and annually through year 10
Secondary outcomes (7)
Jaundice (total serum bilirubin of greater than 2.0 mg/dl)
Measured: Measured at baseline and annually through year 10
Listing for liver transplantation
Measured: Measured at baseline and annually through year 10
Calculated Pediatric End-Stage Liver Disease (PELD) score for participants less than 12 years of age or Model for End-Stage Liver Disease (MELD) score for participants 12 years of age or older
Measured: Measured at baseline and annually through year 10
Health related quality of life
Measured: Measured at baseline and annually through year 10
Growth (length and weight Z-score)
Measured: Measured at baseline and annually through year 10
Bone mineral density (lumbar and spine total body)
Measured: Measured at baseline in ALGS and PFIC/BRIC subjects
Presence of hearing loss (ALGS and PFIC)
Measured: Measured at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2007 (estimated)
- Study start30 Nov 2007
- Primary completion31 May 2029 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Liver DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,675 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arbor Research Collaborative for Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kathleen Loomes, MD, Study chair, Children's Hospital of PhiladelphiaEd Doo, MD, Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)John Magee, MD, Principal investigator, University of MichiganLisa Henn, PhD, Principal investigator, Arbor Research Collaborative for HealthKatrina Loh, MD, Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00571272
- Sponsor's protocol ID
- LOGIC Study - ChiLDReN Network
- Other IDs
- U01DK103149, U01DK103140, U01DK103135, U01DK084575, U01DK084538, U01DK084536, U01DK062503, U01DK062500
- Acronym
- LOGIC
- Status last verified
- Jun 2026
- First submitted
- 7 Dec 2007
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The data will be transferred to NIDDK at the end of the study.
Publications
Teckman J, Rosenthal P, Ignacio RV, Spino C, Bass LM, Horslen S, Wang K, Magee JC, Karpen S, Asai A, Molleston JP, Squires RH, Kamath BM, Guthery SL, Loomes KM, Shneider BL, Sokol RJ; ChiLDReN (Childhood Liver Disease Research Network). Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance. Hepatol Commun. 2023 Dec 7;7(12):e0345. doi: 10.1097/HC9.0000000000000345. eCollection 2023 Dec 1.
PubMed 38055647Leung DH, Sorensen LG, Ye W, Hawthorne K, Ng VL, Loomes KM, Fredericks EM, Alonso EM, Heubi JE, Horslen SP, Karpen SJ, Molleston JP, Rosenthal P, Sokol RJ, Squires RH, Wang KS, Kamath BM, Magee JC; Childhood Liver Disease Research Network (ChiLDReN). Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver. J Pediatr Gastroenterol Nutr. 2022 Jan 1;74(1):96-103. doi: 10.1097/MPG.0000000000003337.
PubMed 34694263Teckman JH, Rosenthal P, Abel R, Bass LM, Michail S, Murray KF, Rudnick DA, Thomas DW, Spino C, Arnon R, Hertel PM, Heubi J, Kamath BM, Karnsakul W, Loomes KM, Magee JC, Molleston JP, Romero R, Shneider BL, Sherker AH, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Baseline Analysis of a Young alpha-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension. J Pediatr Gastroenterol Nutr. 2015 Jul;61(1):94-101. doi: 10.1097/MPG.0000000000000753.
PubMed 25651489
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC)
- ClinicalTrials.gov ID
- NCT00571272
- Acronym / sponsor ID
- LOGIC / LOGIC Study - ChiLDReN Network
- Keywords
- Cholestatic Liver Disease, Cholestasis, Childhood Diseases, Genetic Diseases, Bile Acid Synthesis and Metabolism Defects, Progressive Familial Intrahepatic Cholestasis
- Study type
- Observational
- Recruitment status
- Suspended
- Enrolment
- 1,675 participants (estimated)
- Lead sponsor
- Arbor Research Collaborative for HealthUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 30 Nov 2007 (actual)
- Primary completion
- 31 May 2029 (estimated)
- Study completion
- 31 May 2029 (estimated)
- First posted
- 11 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cholestasis is a condition in which bile is not properly transported from the liver to the small intestine. Cholestasis can be caused by an array of childhood diseases, including the genetic diseases Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis and metabolism defects, and progressive familial intrahepatic cholestasis (PFIC) or benign recurrent intrahepatic cholestasis(BRIC). This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.
Detailed description
Cholestasis is a rare condition that involves a reduction or obstruction of bile flow from the liver to the small intestine. When bile flow is hindered, a waste product pigment called bilirubin can escape into the bloodstream and build up to harmful levels. This may lead to the easily recognizable cholestatic symptoms of jaundice, itching, and impaired growth and eventually to more serious health problems. Four rare genetic liver disorders- ALGS, a-1AT, bile acid synthesis and metabolism defects, and PFIC-account for about 20% to 30% of all infant cases of cholestasis. These four disorders compose a group of related diseases that can cause significant growth problems during childhood, serious liver problems, the need for liver transplantation, and potentially death. More research on these rare liver diseases is necessary to develop a scientific basis for improvement in diagnostic techniques and treatments. Current diagnostic procedures are complex, and the development of simpler diagnostic tests would facilitate early diagnosis and treatment. This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.
Participants who have been previously enrolled into this study will be followed for 20 years, until transplanted, or death. Study visits will involve review of clinical information, family history, and any clinically indicated treatments and their outcomes; a physical exam; laboratory tests; and radiologic and imaging evaluations.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Infants less than 6 months old with a cholestatic liver disease who were initially enrolled into the Childhood Liver Disease Research and Education Network (ChiLDREN) Prospective Biliary Atresia Epidemiology study (PROBE study; P003) |
| 2 | – | –Participants with a cholestatic liver disease who are between birth and 25 years old who were NOT initially enrolled into the Childhood Liver Disease Research and Education Network (ChiLDREN) Prospective Biliary Atresia Epidemiology study (PROBE study; P003) |
| 3 | – | –Post-liver transplant participants with a cholestatic liver disease who are between 1 day and 25 years old. Affected parents of patients enrolled in the study are eligible for enrollment if they are 25 years old or less |
| 5 | – | –Affected siblings (without evidence of liver disease) of Alpha-1 Antitrypsin Deficiency participants who are enrolled in LOGIC. |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- The study population will consist of 400 participants with Alagille syndrome, 400 with alpha-1 trypsin deficieny (of which up to 25 may be siblings of participants), 300 with PFIC (or BRIC), and 50 with bile acid synthesis defects.
Key inclusion criteria (5 listed)
- Children and young adults diagnosed with one of the four cholestatic diseases from birth through 25 years old.
- Siblings of participants with alpha-1-antitrypsin deficiency, who are affected with alpha-1-antitrypsin deficiency, but have no evidence of liver disease.
- Both sexes, all races and ethnic groups.
- Participant meets the enrollment criteria for one of the four cholestatic liver diseases.
- Patient and/or parent/legal guardian have the ability to provide written informed consent for enrollment.
Key exclusion criteria (1 listed)
- 1. Inability to comply with the longitudinal follow-up described in the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Demonstration of disease progression for each of the four cholestatic liver diseases of the study, including liver transplantation, death, growth failure, worsening liver function, and developmental complications of portal high blood pressure
Time frame: Measured at baseline and annually through year 10
7 secondary outcomes
Jaundice (total serum bilirubin of greater than 2.0 mg/dl)
Time frame: Measured at baseline and annually through year 10
Listing for liver transplantation
Time frame: Measured at baseline and annually through year 10
Calculated Pediatric End-Stage Liver Disease (PELD) score for participants less than 12 years of age or Model for End-Stage Liver Disease (MELD) score for participants 12 years of age or older
Time frame: Measured at baseline and annually through year 10
Health related quality of life
Time frame: Measured at baseline and annually through year 10
Growth (length and weight Z-score)
Time frame: Measured at baseline and annually through year 10
Bone mineral density (lumbar and spine total body)
Time frame: Measured at baseline in ALGS and PFIC/BRIC subjects
Presence of hearing loss (ALGS and PFIC)
Time frame: Measured at baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Derived from this study: PubMed 38055647Teckman J, Rosenthal P, Ignacio RV, Spino C, Bass LM, Horslen S, Wang K, Magee JC, Karpen S, Asai A, Molleston JP, Squires RH, Kamath BM, Guthery SL, Loomes KM, Shneider BL, Sokol RJ; ChiLDReN (Childhood Liver Disease Research Network). Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance. Hepatol Commun. 2023 Dec 7;7(12):e0345. doi: 10.1097/HC9.0000000000000345. eCollection 2023 Dec 1.
- Derived from this study: PubMed 34694263Leung DH, Sorensen LG, Ye W, Hawthorne K, Ng VL, Loomes KM, Fredericks EM, Alonso EM, Heubi JE, Horslen SP, Karpen SJ, Molleston JP, Rosenthal P, Sokol RJ, Squires RH, Wang KS, Kamath BM, Magee JC; Childhood Liver Disease Research Network (ChiLDReN). Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver. J Pediatr Gastroenterol Nutr. 2022 Jan 1;74(1):96-103. doi: 10.1097/MPG.0000000000003337.
- Derived from this study: PubMed 25651489Teckman JH, Rosenthal P, Abel R, Bass LM, Michail S, Murray KF, Rudnick DA, Thomas DW, Spino C, Arnon R, Hertel PM, Heubi J, Kamath BM, Karnsakul W, Loomes KM, Magee JC, Molleston JP, Romero R, Shneider BL, Sherker AH, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN). Baseline Analysis of a Young alpha-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension. J Pediatr Gastroenterol Nutr. 2015 Jul;61(1):94-101. doi: 10.1097/MPG.0000000000000753.
- Childhood Liver Disease Research Network (ChiLDReN) websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The data will be transferred to NIDDK at the end of the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathleen Loomes, MD study chair
Children's Hospital of Philadelphia
Ed Doo, MD study director
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
John Magee, MD principal investigator
University of Michigan
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Diseases and Alagille Syndrome, run by Arbor Research Collaborative for Health at 17 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Demonstration of disease progression for each of the four cholestatic liver diseases of the study, including liver transplantation, death, growth failure, worsening liver function, and developmental complications of portal high blood pressure (time frame: Measured at baseline and annually through year 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00571272, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.