Primary Biliary CirrhosisPhase 1MSCsTreatPBCNCT01440309
Efficacy and Safety Study of Allogenic Mesenchymal Stem Cells for Patients With Refractory Primary Biliary Cirrhosis
A Phase 1 study testing Biological: mesenchymal stem cell and ursodeoxycholic acid in people with Primary Biliary Cirrhosis, run by Robert Chunhua Zhao, MD, PhD at 1 site in China.
Trial summary
The study is designed to evaluate the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells for patients with refractory primary biliary cirrhosis (PBC). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- Biological: mesenchymal stem cell and ursodeoxycholic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Nov 2011to Dec 2013
- Phase
- Phase 1
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- There must be at least two of the following: a concentration in serum of AMAs at titres of 1:40 or higher; an unexplained rise in the amount of alkaline phosphatase of at least 1•5 times the upper limit of normal for more than 24 weeks; and compatible liver histological findings, specifically non-suppurative cholangitis and interlobular bile duct injury.
- Incomplete response to UDCA at 13-15 mg/kg/day, Criteria for the group of complete responders is including: concentrations of alkaline phosphatase less than three times the upper limit of normal, aspartate aminotransferase less than twice the upper limit of normal, and bilirubin less than 17 μmol/L;and normalisation of abnormal concentrations of bilirubin, albumin, or both.
- Liver pathological staging in 2 or3, Histological staging is based on Ludwig's and Scheuer's classifications
Who cannot join
- Patients are receiving any other investigational agents within 4 weeks of study entry
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia
- In pregnancy or lactation
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- HCVpositive ，HBSAg positive or with other liver diseases
- Combined with other autoimmune disease
Show all 9Show fewer
- Expected survival time is less than one year
- Decompensation of liver function（Child B or C）
- Have a history of allergy or Allergic constitution
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing
Fengchun Zhang, MD, zhangfccra@yahoo.com.cn
About this study
Official title: Phase I Clinical Trial, Randomized, Controlled, to Evaluate the Efficacy and Safety of Therapy With Allogenic Mesenchymal Stem Cells From Bone Marrow for Patients With Refractory Primary Biliary Cirrhosis
The study is designed to evaluate the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells for patients with refractory primary biliary cirrhosis (PBC).
Read the detailed description
Primary biliary cirrhosis (PBC) is an organ-specific inflammatory disease and characterized by immune mediated destruction of intrahepatic bile ducts, then lead to liver cirrhosis and eventually failure.Currently, ursodeoxycholic acid (UDCA) is the only drug approved by the Food and Drug Administration (FDA). Novel treatment is urgently needed for patients who have an incomplete response to UDCA. Mesenchymal stem cells (MSC) represent a promising tool for cell-based therapies of autoimmune diseases. To explore the therapeutic effect of MSCs for PBC, the investigators plan to conduct an open-label, randomized clinical trial. Patients with PBC will be enrolled and randomly divided into two groups which will receive MSCs and UDCA respectively. The investigators will evaluate the efficacy and safety of MSCs for PBC by comparison of symptom improvement, survival rate and side effects in the two groups.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- Biological: mesenchymal stem cell, ursodeoxycholic acid
- Keywords
- biliary cirrhosis
- 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.
Biological: mesenchymal stem cellBiological
Also called regenerative medicine:MSCs
Mesenchymal stem cells,5-50 million/kg, Intravenous infusion, One dosage，whether to give another dosage depending on patients' condition
ursodeoxycholic acidDrug
Also called UDCA
13-15 mg/kg/day, to the end of the study
| Study group | Role | What they receive |
|---|---|---|
| allogenic mesenchymal stem cells (MSCs) | Experimental | Patients who have primary biliary cirrhosis. Receives: Biological: Biological: mesenchymal stem cell |
| ursodeoxycholic acid (UDCA) | Active comparator | Patients who have primary biliary cirrhosis. Receives: Drug: ursodeoxycholic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
serum level of alkaline phosphatase
Serum level of alkaline phosphatase will be measured at entry, 1 months，3 months, 6 months and 24 months after therapy
Measured: 24 months after MSCs administration
Secondary outcomes (6)
histological changes in liver biopsies
Liver biopsy of each patient will be taken before entry into therapeutic trials and at 6 months after therapy.
Measured: 6 months after therapy
Serum levels of TNF-alpha
serum levels of TNF-alpha will be assessed before entry into therapeutic trials and at 6 months after therapy
Measured: 6 months after therapy
changes in fatigue
changes in fatigue will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by PBC-40 score.
Measured: 6 months after theraphy
The occurrence of cirrhosis and its complications
Measured: 24 months after therapy
Serum levels of Interleukin
serum levels of Interleukin will be assessed before entry into therapeutic trials and at 6 months after therapy
Measured: 6 months after therapy
changes in pruritus severity
changes in pruritus severity will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by VAS score.
Measured: 6 months after therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Robert Chunhua Zhao, MD, PhD
- Collaborators
- Peking Union Medical College Hospital
- Responsible party
- Sponsor-investigator, Robert Chunhua Zhao, MD, PhD, Chinese Academy of Medical Sciences
- Investigators
- Fengchun Zhang, MD, Principal investigator, Peking Union Medical College HospitalRobert Chunhua Zhao, MD,PhD, Principal investigator, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01440309
- Sponsor's protocol ID
- 2008BAI59B03/2011AA020119
- Acronym
- MSCsTreatPBC
- Status last verified
- Sep 2011
- First submitted
- 20 Sep 2011
- Last updated
- 3 Aug 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sun Z, Han Q, Zhu Y, Li Z, Chen B, Liao L, Bian C, Li J, Shao C, Zhao RC. NANOG has a role in mesenchymal stem cells' immunomodulatory effect. Stem Cells Dev. 2011 Sep;20(9):1521-8. doi: 10.1089/scd.2010.0366. Epub 2011 Feb 26.
PubMed 21235326Shi D, Liao L, Zhang B, Liu R, Dou X, Li J, Zhu X, Yu L, Chen D, Zhao RC. Human adipose tissue-derived mesenchymal stem cells facilitate the immunosuppressive effect of cyclosporin A on T lymphocytes through Jagged-1-mediated inhibition of NF-kappaB signaling. Exp Hematol. 2011 Feb;39(2):214-224.e1. doi: 10.1016/j.exphem.2010.10.009. Epub 2010 Nov 13.
PubMed 21078360Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood. 2009 Jan 1;113(1):46-57. doi: 10.1182/blood-2008-04-154138. Epub 2008 Oct 2.
PubMed 18832657Liao L, Zhao RC. An overview of stem cell-based clinical trials in China. Stem Cells Dev. 2008 Aug;17(4):613-8. doi: 10.1089/scd.2008.0183.
PubMed 18673001Fang B, Shi M, Liao L, Yang S, Liu Y, Zhao RC. Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplantation. 2004 Jul 15;78(1):83-8. doi: 10.1097/01.tp.0000128326.95294.14.
PubMed 15257043Wang J, Bian C, Liao L, Zhu Y, Li J, Zeng L, Zhao RC. Inhibition of hepatic stellate cells proliferation by mesenchymal stem cells and the possible mechanisms. Hepatol Res. 2009 Dec;39(12):1219-28. doi: 10.1111/j.1872-034X.2009.00564.x. Epub 2009 Sep 25.
PubMed 19788697Chen L, Zhang W, Yue H, Han Q, Chen B, Shi M, Li J, Li B, You S, Shi Y, Zhao RC. Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells. Stem Cells Dev. 2007 Oct;16(5):719-31. doi: 10.1089/scd.2007.0065.
PubMed 17999594Deng W, Han Q, Liao L, You S, Deng H, Zhao RC. Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol. 2005 Jul;24(7):458-63. doi: 10.1089/dna.2005.24.458.
PubMed 16008514Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z, You S, Deng H, Zhao RC. Allogeneic bone marrow-derived flk-1+Sca-1- mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance. Exp Hematol. 2004 Sep;32(9):861-7. doi: 10.1016/j.exphem.2004.06.009.
PubMed 15345288Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004 Jun;13(3):263-71. doi: 10.1089/154732804323099190.
PubMed 15186722
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial, Randomized, Controlled, to Evaluate the Efficacy and Safety of Therapy With Allogenic Mesenchymal Stem Cells From Bone Marrow for Patients With Refractory Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT01440309
- Acronym / sponsor ID
- MSCsTreatPBC / 2008BAI59B03/2011AA020119
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- biliary cirrhosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Robert Chunhua Zhao, MD, PhD
- Collaborators
- Peking Union Medical College Hospital
- Study start
- Nov 2011
- Primary completion
- Nov 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 26 Sep 2011 (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.
The study is designed to evaluate the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells for patients with refractory primary biliary cirrhosis (PBC).
Detailed description
Primary biliary cirrhosis (PBC) is an organ-specific inflammatory disease and characterized by immune mediated destruction of intrahepatic bile ducts, then lead to liver cirrhosis and eventually failure.Currently, ursodeoxycholic acid (UDCA) is the only drug approved by the Food and Drug Administration (FDA). Novel treatment is urgently needed for patients who have an incomplete response to UDCA. Mesenchymal stem cells (MSC) represent a promising tool for cell-based therapies of autoimmune diseases. To explore the therapeutic effect of MSCs for PBC, the investigators plan to conduct an open-label, randomized clinical trial. Patients with PBC will be enrolled and randomly divided into two groups which will receive MSCs and UDCA respectively. The investigators will evaluate the efficacy and safety of MSCs for PBC by comparison of symptom improvement, survival rate and side effects in the two groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| allogenic mesenchymal stem cells (MSCs) | Experimental | Biological: Biological: mesenchymal stem cellPatients who have primary biliary cirrhosis. |
| ursodeoxycholic acid (UDCA) | Active comparator | Drug: ursodeoxycholic acidPatients who have primary biliary cirrhosis. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- There must be at least two of the following: a concentration in serum of AMAs at titres of 1:40 or higher; an unexplained rise in the amount of alkaline phosphatase of at least 1•5 times the upper limit of normal for more than 24 weeks; and compatible liver histological findings, specifically non-suppurative cholangitis and interlobular bile duct injury.
- Incomplete response to UDCA at 13-15 mg/kg/day, Criteria for the group of complete responders is including: concentrations of alkaline phosphatase less than three times the upper limit of normal, aspartate aminotransferase less than twice the upper limit of normal, and bilirubin less than 17 μmol/L;and normalisation of abnormal concentrations of bilirubin, albumin, or both.
- Liver pathological staging in 2 or3, Histological staging is based on Ludwig's and Scheuer's classifications
Key exclusion criteria (9 listed)
- Patients are receiving any other investigational agents within 4 weeks of study entry
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia
- In pregnancy or lactation
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- HCVpositive ，HBSAg positive or with other liver diseases
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 |
|---|---|---|
| Biological: mesenchymal stem cellAlso: regenerative medicine:MSCsMesenchymal stem cells,5-50 million/kg, Intravenous infusion, One dosage，whether to give another dosage depending on patients' condition | Biological | allogenic mesenchymal stem cells (MSCs) |
| ursodeoxycholic acidAlso: UDCA13-15 mg/kg/day, to the end of the study | Drug | ursodeoxycholic acid (UDCA) |
Primary outcome
serum level of alkaline phosphatase
Time frame: 24 months after MSCs administration
Serum level of alkaline phosphatase will be measured at entry, 1 months，3 months, 6 months and 24 months after therapy
6 secondary outcomes
histological changes in liver biopsies
Time frame: 6 months after therapy
Serum levels of TNF-alpha
Time frame: 6 months after therapy
changes in fatigue
Time frame: 6 months after theraphy
The occurrence of cirrhosis and its complications
Time frame: 24 months after therapy
Serum levels of Interleukin
Time frame: 6 months after therapy
changes in pruritus severity
Time frame: 6 months after therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2012.
- Background: PubMed 21235326Sun Z, Han Q, Zhu Y, Li Z, Chen B, Liao L, Bian C, Li J, Shao C, Zhao RC. NANOG has a role in mesenchymal stem cells' immunomodulatory effect. Stem Cells Dev. 2011 Sep;20(9):1521-8. doi: 10.1089/scd.2010.0366. Epub 2011 Feb 26.
- Background: PubMed 21078360Shi D, Liao L, Zhang B, Liu R, Dou X, Li J, Zhu X, Yu L, Chen D, Zhao RC. Human adipose tissue-derived mesenchymal stem cells facilitate the immunosuppressive effect of cyclosporin A on T lymphocytes through Jagged-1-mediated inhibition of NF-kappaB signaling. Exp Hematol. 2011 Feb;39(2):214-224.e1. doi: 10.1016/j.exphem.2010.10.009. Epub 2010 Nov 13.
- Background: PubMed 18832657Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood. 2009 Jan 1;113(1):46-57. doi: 10.1182/blood-2008-04-154138. Epub 2008 Oct 2.
- Background: PubMed 18673001Liao L, Zhao RC. An overview of stem cell-based clinical trials in China. Stem Cells Dev. 2008 Aug;17(4):613-8. doi: 10.1089/scd.2008.0183.
- Background: PubMed 15257043Fang B, Shi M, Liao L, Yang S, Liu Y, Zhao RC. Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplantation. 2004 Jul 15;78(1):83-8. doi: 10.1097/01.tp.0000128326.95294.14.
- Background: PubMed 19788697Wang J, Bian C, Liao L, Zhu Y, Li J, Zeng L, Zhao RC. Inhibition of hepatic stellate cells proliferation by mesenchymal stem cells and the possible mechanisms. Hepatol Res. 2009 Dec;39(12):1219-28. doi: 10.1111/j.1872-034X.2009.00564.x. Epub 2009 Sep 25.
- Background: PubMed 17999594Chen L, Zhang W, Yue H, Han Q, Chen B, Shi M, Li J, Li B, You S, Shi Y, Zhao RC. Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells. Stem Cells Dev. 2007 Oct;16(5):719-31. doi: 10.1089/scd.2007.0065.
- Background: PubMed 16008514Deng W, Han Q, Liao L, You S, Deng H, Zhao RC. Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol. 2005 Jul;24(7):458-63. doi: 10.1089/dna.2005.24.458.
- Background: PubMed 15345288Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z, You S, Deng H, Zhao RC. Allogeneic bone marrow-derived flk-1+Sca-1- mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance. Exp Hematol. 2004 Sep;32(9):861-7. doi: 10.1016/j.exphem.2004.06.009.
- Background: PubMed 15186722Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004 Jun;13(3):263-71. doi: 10.1089/154732804323099190.
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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.
Fengchun Zhang, MD principal investigator
Peking Union Medical College Hospital
Robert Chunhua Zhao, MD,PhD principal investigator
Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biological: mesenchymal stem cell and ursodeoxycholic acid in people with Primary Biliary Cirrhosis, run by Robert Chunhua Zhao, MD, PhD 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 9 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 3 Aug 2012. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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 Fengchun Zhang, MD (0086-10-65296891, zhangfccra@yahoo.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
serum level of alkaline phosphatase (time frame: 24 months after MSCs administration). 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 NCT01440309, which also lists 10 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 3 Aug 2012.