Primary Biliary CirrhosisPhase 1/2NCT01662973
Umbilical Cord Mesenchymal Stem Cells for Patients With Primary Biliary Cirrhosis
A Phase 1/2 study testing conventional plus UC-MSC treatment in people with Primary Biliary Cirrhosis, run by Beijing 302 Hospital at 1 site in China.
Trial summary
Primary biliary cirrhosis (PBC) is a slowly progressive disease that causes substantial loss of intrahepatic bile ducts, ultimately resulting in cholestasis, advanced fibrosis, cirrhosis, liver failure and even hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- conventional plus UC-MSC treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- Oct 2011to Oct 2013
- Phase
- Phase 1/2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Primary Biliary Cirrhosis (according to the criteria defined by AASLD practice guidelines , Hepatology, 2009;50:291-308 )
- Negative pregnancy test (female patients in fertile age)
Who cannot join
- Hepatocellular carcinoma or other Malignancies
- Pregnant or lactating women
- Viral Hepatitis ( HAB, HBV, HCV, et al )
- Vital organs failure (Cardiac, Renal or Respiratory, et al)
- Sepsis
- Active thrombosis in the portal or hepatic veins
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing 302 Hospital
Beijing, Beijing Municipality, 100039
Fu-Sheng Wang, professor, 86-10-63879735 ext. 2015.12, fswang302@163.com
Lifeng Wang, Doctor, 86-10-63879735 ext. 2015.12, wanglf76@gmail.com
About this study
Official title: Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Primary Biliary Cirrhosis
Primary biliary cirrhosis (PBC) is a slowly progressive disease that causes substantial loss of intrahepatic bile ducts, ultimately resulting in cholestasis, advanced fibrosis, cirrhosis, liver failure and even hepatocellular carcinoma. Histologically, the disease is characterized by chronic portal inflammation with infiltration, destruction and loss of the epithelial cells in the small-sized and medium-sized bile ducts. Currently, Ursodeoxycholic acid (UDCA) in a dose of 13-15mg/kg/day is recommended as therapeutic drugs for PBC by AASLD and is approved for this indication by the U.S. Food and Drug Administration (FDA). Treatment with UDCA may delay disease progression and prolong survival free of liver transplantation. However, one out of three patients does not adequately respond to UDCA therapy and many need additional medical therapy or liver transplantation, or both. UC-MSC has been application for the treatment of several severe autoimmune diseases, such as immune thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis. In this study, the safety and efficacy of UC-MSC transplantation for PBC patients will be evaluated.
Read the detailed description
Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic disease associated with the development of cirrhosis and liver failure that may justify liver transplantation. Ursodeoxycholic acid (UDCA) is currently the only drug approved specifically for the treatment of PBC. However, one out of three patients does not adequately respond to UDCA therapy and many need additional medical therapy or liver transplantation, or both.
The potential for stem cells to differentiate into biliary epithelial cells was recently confirmed. In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been applicated in the clinic for treat several human disease such as GVHD, cardiac injury and brain injury, and displayed good tolerance and efficiency. Recently, umbilical cord-derived MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as therapy-resistant rheumatoid arthritis and multiple sclerosis.
The purpose of this study is to learn whether and how UC-MSC can improve the disease condition in patients with primary biliary cirrhosis. This study will also look at how well UC-MSC is tolerated and its safety in PBC patients
Participants in the study will be randomly assigned to one of two treatment arms:
Arm A: Participants will receive 12 weeks of UC-MSC treatment plus UDCA. Arm B: Participants will receive 12 weeks of placebo plus UDCA. UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anticoagulant. UC-MSCs are given via i.v. under sonography monitoring. After cell therapy, patients are followed up at week 4,8,12,24,36 and 48. The evaluation of some clinical parameters such as the level of serum alkaline phosphatase (ALP), alanine aminotransferase(ALT) aspartate aminotransferase (AST) and total bilirubin (TB), prothrombin time(PT), albumin(ALB), prealbumin(PA), are detected at these time points. Mayo risk score, portal hypertension, Liver histology, MELD score and clinical symptoms were also observed simultaneously.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- conventional plus UC-MSC treatment, Conventional plus placebo treatment
- Keywords
- Primary Biliary Cirrhosis, Mesenchymal Stem Cells, Serum alkaline phosphatase, Serum Bilirubin
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
conventional plus UC-MSC treatmentOther
Received conventional treatment and taken i.v., once per 4 week, at a dose of 1*10E6 UC-MSC/kg body weight for 12 weeks.
Conventional plus placebo treatmentOther
Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Conventional plus UC-MSC treatment | Experimental | Participants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit.
Participants will then be followed until the week 48 study visit. Receives: Other: conventional plus UC-MSC treatment |
| Conventional plus placebo treatment | Placebo comparator | Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit. Receives: Other: Conventional plus placebo treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum alkaline phosphatase (ALP)
Measured: 0, 4, 8,12, 24, 36,48 weeks after treatment
Secondary outcomes (7)
Histological changes in liver biopsies
Measured: baseline and 48 weeks
Serum Bilirubin
Measured: At base line and at week 4,8,12,24,36 and 48
Serum AST
Measured: At base line and at week 4,8,12,24,36 and 48
Mayo risk score
Measured: At base line and at week 4,8,12,24,36 and 48
Number of patients with Portal Hypertension after 12 weeks treatment
Measured: At base line and at week 12,24,36 and 48
MELD score
Measured: At base line and at week 4,8,12,24,36 and 48
Number of participants with improvement of clinical symptoms
clinical symptoms including fatigue (Fatigue Impact Score, FIS) and pruritus ( Visual Analog Scale ,VAS)
Measured: At base line and at week 4,8,12,24,36 and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2012 (estimated)
- Study startOct 2011
- Primary completionOct 2013 (estimated)
- Study completionOct 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary CirrhosisStudies 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fu-Sheng Wang, Beijing 302 Hospital
- Investigators
- Fu-Sheng Wang, professor, Principal investigator, Beijing 302 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01662973
- Sponsor's protocol ID
- Beijing302-005
- Status last verified
- May 2013
- First submitted
- 5 Aug 2012
- Last updated
- 31 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology. 1997 Sep;113(3):884-90. doi: 10.1016/s0016-5085(97)70183-5.
PubMed 9287980Kuiper EM, Hansen BE, de Vries RA, den Ouden-Muller JW, van Ditzhuijsen TJ, Haagsma EB, Houben MH, Witteman BJ, van Erpecum KJ, van Buuren HR; Dutch PBC Study Group. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009 Apr;136(4):1281-7. doi: 10.1053/j.gastro.2009.01.003. Epub 2009 Jan 14.
PubMed 19208346Poupon R. Primary biliary cirrhosis: a 2010 update. J Hepatol. 2010 May;52(5):745-58. doi: 10.1016/j.jhep.2009.11.027. Epub 2010 Feb 18.
PubMed 20347176Silveira MG, Brunt EM, Heathcote J, Gores GJ, Lindor KD, Mayo MJ. American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis. Hepatology. 2010 Jul;52(1):349-59. doi: 10.1002/hep.23637. No abstract available.
PubMed 20578151
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT01662973
- Acronym / sponsor ID
- Beijing302-005
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- Primary Biliary Cirrhosis, Mesenchymal Stem Cells, Serum alkaline phosphatase, Serum Bilirubin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Oct 2013 (estimated)
- Study completion
- Oct 2013 (estimated)
- First posted
- 13 Aug 2012 (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.
Primary biliary cirrhosis (PBC) is a slowly progressive disease that causes substantial loss of intrahepatic bile ducts, ultimately resulting in cholestasis, advanced fibrosis, cirrhosis, liver failure and even hepatocellular carcinoma. Histologically, the disease is characterized by chronic portal inflammation with infiltration, destruction and loss of the epithelial cells in the small-sized and medium-sized bile ducts. Currently, Ursodeoxycholic acid (UDCA) in a dose of 13-15mg/kg/day is recommended as therapeutic drugs for PBC by AASLD and is approved for this indication by the U.S. Food and Drug Administration (FDA). Treatment with UDCA may delay disease progression and prolong survival free of liver transplantation. However, one out of three patients does not adequately respond to UDCA therapy and many need additional medical therapy or liver transplantation, or both. UC-MSC has been application for the treatment of several severe autoimmune diseases, such as immune thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis. In this study, the safety and efficacy of UC-MSC transplantation for PBC patients will be evaluated.
Detailed description
Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic disease associated with the development of cirrhosis and liver failure that may justify liver transplantation. Ursodeoxycholic acid (UDCA) is currently the only drug approved specifically for the treatment of PBC. However, one out of three patients does not adequately respond to UDCA therapy and many need additional medical therapy or liver transplantation, or both.
The potential for stem cells to differentiate into biliary epithelial cells was recently confirmed. In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been applicated in the clinic for treat several human disease such as GVHD, cardiac injury and brain injury, and displayed good tolerance and efficiency. Recently, umbilical cord-derived MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as therapy-resistant rheumatoid arthritis and multiple sclerosis.
The purpose of this study is to learn whether and how UC-MSC can improve the disease condition in patients with primary biliary cirrhosis. This study will also look at how well UC-MSC is tolerated and its safety in PBC patients
Participants in the study will be randomly assigned to one of two treatment arms:
Arm A: Participants will receive 12 weeks of UC-MSC treatment plus UDCA. Arm B: Participants will receive 12 weeks of placebo plus UDCA. UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anticoagulant. UC-MSCs are given via i.v. under sonography monitoring. After cell therapy, patients are followed up at week 4,8,12,24,36 and 48. The evaluation of some clinical parameters such as the level of serum alkaline phosphatase (ALP), alanine aminotransferase(ALT) aspartate aminotransferase (AST) and total bilirubin (TB), prothrombin time(PT), albumin(ALB), prealbumin(PA), are detected at these time points. Mayo risk score, portal hypertension, Liver histology, MELD score and clinical symptoms were also observed simultaneously.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional plus UC-MSC treatment | Experimental | Other: conventional plus UC-MSC treatmentParticipants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit. |
| Conventional plus placebo treatment | Placebo comparator | Other: Conventional plus placebo treatmentParticipants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Written informed consent
- Primary Biliary Cirrhosis (according to the criteria defined by AASLD practice guidelines , Hepatology, 2009;50:291-308 )
- Negative pregnancy test (female patients in fertile age)
Key exclusion criteria (6 listed)
- Hepatocellular carcinoma or other Malignancies
- Pregnant or lactating women
- Viral Hepatitis ( HAB, HBV, HCV, et al )
- Vital organs failure (Cardiac, Renal or Respiratory, et al)
- Sepsis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| conventional plus UC-MSC treatmentReceived conventional treatment and taken i.v., once per 4 week, at a dose of 1*10E6 UC-MSC/kg body weight for 12 weeks. | Other | Conventional plus UC-MSC treatment |
| Conventional plus placebo treatmentReceived conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks | Other | Conventional plus placebo treatment |
Primary outcome
Serum alkaline phosphatase (ALP)
Time frame: 0, 4, 8,12, 24, 36,48 weeks after treatment
7 secondary outcomes
Histological changes in liver biopsies
Time frame: baseline and 48 weeks
Serum Bilirubin
Time frame: At base line and at week 4,8,12,24,36 and 48
Serum AST
Time frame: At base line and at week 4,8,12,24,36 and 48
Mayo risk score
Time frame: At base line and at week 4,8,12,24,36 and 48
Number of patients with Portal Hypertension after 12 weeks treatment
Time frame: At base line and at week 12,24,36 and 48
MELD score
Time frame: At base line and at week 4,8,12,24,36 and 48
Number of participants with improvement of clinical symptoms
Time frame: At base line and at week 4,8,12,24,36 and 48
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2013.
- Background: PubMed 9287980Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology. 1997 Sep;113(3):884-90. doi: 10.1016/s0016-5085(97)70183-5.
- Background: PubMed 19208346Kuiper EM, Hansen BE, de Vries RA, den Ouden-Muller JW, van Ditzhuijsen TJ, Haagsma EB, Houben MH, Witteman BJ, van Erpecum KJ, van Buuren HR; Dutch PBC Study Group. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009 Apr;136(4):1281-7. doi: 10.1053/j.gastro.2009.01.003. Epub 2009 Jan 14.
- Background: PubMed 20347176Poupon R. Primary biliary cirrhosis: a 2010 update. J Hepatol. 2010 May;52(5):745-58. doi: 10.1016/j.jhep.2009.11.027. Epub 2010 Feb 18.
- Background: PubMed 20578151Silveira MG, Brunt EM, Heathcote J, Gores GJ, Lindor KD, Mayo MJ. American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis. Hepatology. 2010 Jul;52(1):349-59. doi: 10.1002/hep.23637. No abstract available.
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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.
Fu-Sheng Wang, professor principal investigator
Beijing 302 Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing conventional plus UC-MSC treatment in people with Primary Biliary Cirrhosis, run by Beijing 302 Hospital at 1 site in China.
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 3 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 31 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Fu-Sheng Wang, professor (86-10-63879735 ext. 2015.12, fswang302@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum alkaline phosphatase (ALP) (time frame: 0, 4, 8,12, 24, 36,48 weeks after treatment). 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 NCT01662973, which also lists 4 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 31 May 2013.