Human Immunodeficiency VirusPhase 2NCT01213186
Umbilical Cord Mesenchymal Stem Cells for Immune Reconstitution in HIV-infected Patients
A Phase 2 study testing high dose of MSC and low dose of MSC treatment in people with Human Immunodeficiency Virus and Disorder of Immune Reconstitution, run by Fu-Sheng Wang at 3 sites in China.
Trial summary
HIV-1 infection is characterized by progressive depletion of CD4+ T cells that eventually leads to clinically significant immunodeficiency. A chronic generalized immune activation is now being recognized to be the main driving force for T cell depletion, loss of anti-HIV-1 immunity and disease progression during… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Human Immunodeficiency Virus, Disorder of Immune Reconstitution
- What is being tested?
- high dose of MSC and low dose of MSC treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 3 sitesChina
- Study dates
- Jan 2013to Jun 2016
- Phase
- Phase 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
- HIV infected
- antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 24 months after study entry
- CD4 count less than or equal to 250 cells/mm3 continuously and more than 50 cells/mm3 before entry and at screening, obtained within 30 days prior to study entry
- Viral load less than or equal to 50 copies/mL obtained within 30 days prior to study entry
- Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
- Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
Show all 9Show fewer
- No history of CDC category C AIDS-related opportunistic infections
- Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry
- Ability and willingness to provide informed consent
Who cannot join
- coinfection with other virus, including serum HCV RNA positive, or one of followings are positive in antiHAV/anti-HDV/anti-HEV plus ALT more than 80 IU/L.
- history of combination with other severe diseases including renal, circulatory, respiratory, digestive, endocrine, neural and immunological diseases and tumors.
- WBC <2.5*10E9/L, platlet counts <50*10E9/L, Hb <80g/L, lactate >2 mmol/L;
- allergic constitution;
- Accepting other immunomodulatory drugs within 6 months prior screening.
- drug addiction;
- other conditions possibly influencing the trial.
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
Beijing 302 Hospital
Beijing, Beijing Municipality, 100039
Zheng Zhang, Doctor, 86-10-63879735 ext. 2015.12, zhangzheng1975@aliyun.com
Fu-Sheng Wang, Professor
- Recruiting
the Yunnan Hospital of Infectious Diseases
Kunming, Yunnan, 650301
Xicheng Wang, Doctor, 86-0871-6256092 ext. 2015.12, wxch62597@21cn.com
Xicheng Wang, doctor
- Recruiting
Xinjiang Hospital of Infectious Diseases
Ürümqi, Xinjiang, 830013
Xiuling Wang, Professor, 0991-6665288, 1125325165@qq.com
Hao Wu, Professor
About this study
Official title: Phase 2 Study of UC-MSC in Restoring CD4 T Cell Counts and Reducing Immune Activation in HIV-infected Patients Underlying Long-term Antiviral Therapy: a Multicenter, Does-escalating, Randomized, Double-blind, Controlled Trial.
HIV-1 infection is characterized by progressive depletion of CD4+ T cells that eventually leads to clinically significant immunodeficiency. A chronic generalized immune activation is now being recognized to be the main driving force for T cell depletion, loss of anti-HIV-1 immunity and disease progression during chronic HIV-1 infection. However, it is still unknown whether reducing immune activation will restore CD4 T cell counts and leading to immune reconstitution in chronic HIV infection. Mesenchymal stem cells (MSC) have been demonstrated to decrease immune responses of the host, and can suppress inflammation in HIV-infected non-responders. Here, the investigators propose a hypothesis that MSC can reduce immune activation which subsequently lead to the restoration of CD4 T-cell counts dependent on dose of transfused MSCs in HIV-infected patients.
Read the detailed description
Although HIV-1 infection is characterized by progressive depletion of CD4+ T cells that eventually leads to clinically significant immunodeficiency, a chronic generalized immune activation is now being recognized to be the main driving force for T cell depletion, loss of anti-HIV-1 immunity and disease progression during chronic HIV-1 infection. In particular, this immune activation has been identified as a disease determinant independent of viral load or cell death in HIV-1 infection. A series of clinical evidences have indicated that activated CD8 T cells may attack body cells infected with viruses. Because of this, CD4 cells infected with HIV are frequently destroyed by CD8 cells.
Mesenchymal stem cells (MSCs) are the adult stem cells originating from the mesenchymal and connective tissue of bone marrow, adipose tissue, placenta, umbilical cord, cord blood, peripheral blood, liver, etc. These cells show immunomodulation, self-renewal, and multi-directional differentiation potential. In particular, MSCs have recently emerged as promising candidates for cell-based immunotherapy because they can modulate the immune response in various ways. A series of studies have indicated that secretion of dissoluble cytokines and direct contact with MSCs can block the development and functioning of antigen-presenting cells, inhibit the differentiation of B cells, and suppress the immune response of T cells and natural killer cells. The immunosuppressive effect of infused MSCs has been successfully employed in the treatment of acute severe graft-versus-host disease (GVHD). Thus, MSC may reduce inflammatory responses and promote tissue recovery in human diseases.
The purpose of this study is to learn what dose of transfused MSC reduces the level of activation of CD8 cells in people infected with HIV. The decreased activation of CD8 cells may lead to a more CD4 T cell restoration in HIV infection. This study will also look at what dose of MSCs is tolerated and its safety in HIV- infected patients.
Participants in this study will be randomly assigned to one of three treatment arms:
Arm A:Participants will receive 48 weeks of low dose of MSC treatment followed by 48-week follow-up observation.
Arm B:Participants will receive 48 weeks of high dose of MSC treatment followed by 48-week follow-up observation.
Arm C: Participants will receive 48 weeks of saline placebo followed by 48-week follow-up observation.
Study treatment will be given at 0, 4, 12, 24, 36 and 48 week since the onset of treatment. There will be an additional 48 weeks of follow-up for purposes of safety. After treatment has started, participants will be asked to come to the clinic on Weeks 4, 12, 24, 36, 48,60,72,84 and 96. At each visit participants will receive enough study treatment to last until the next visit. Each visit will last between 2 and 3 hours. At most visits participants will have a physical exam, answer questions about any medications they are taking and how they are feeling, and have blood drawn for safety to assess CD4/CD8 cell counts and viral load. Some additional blood will also be stored for immunology testing. At some visits participants will be asked questions about their medication and medical history, have pupils dilated, have a hearing test, and have an electrocardiogram (EKG). Some visits will require participants to arrive fasting. Pregnancy tests may also be conducted if the participant is able to become pregnant or if pregnancy is suspected.
- Being tested
- high dose of MSC, low dose of MSC treatment
- Keywords
- stem cell, hiv, CD4, immune activation
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
high dose of MSCDrug
Also called MSC treatment dose
Taken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 1.5*10E6/kg for 48 weeks.
low dose of MSC treatmentDrug
Also called MSC low dose
Taken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 0.5*10E6/kg for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Drug: high dose of MSC treatment | Experimental | Participants will receive high dose of MSC from Day 0 through the Week 48 study visit. Participants will then be followed until the Week 48 study visit. Receives: Drug: high dose of MSC |
| low dose of MSC treatment | Experimental | Participants will receive a low dose of MSC treatment from Day 0 through the Week 48 study visit, and then follow-ed up for additional 48 weeks. Receives: Drug: low dose of MSC treatment |
| low dose of MSC | Placebo comparator | Participants will receive a saline placebo treatment from Day 0 through the Week 48 study visit, and then follow-ed up for additional 48 weeks. |
What is being measured
The primary outcome is the main question the study is designed to answer.
the total CD4 T cell counts compared with CD4 T cell counts at baseline
Measured: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
Secondary outcomes (8)
the CD38 expression on CD8 T cells
Measured: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: at baseline and up to week 96
plasma RNA copies/mL
Measured: At Entry and at Weeks 24, 48, 72, 96
the ratio of CD4 and CD8 T cells
Measured: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
the HLA-DR expression on CD8 T cells
Measured: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
Quality of live
Measured: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
the occurring rate of tumor
Measured: At Baseline and at week 24, 48, 72, 96
occurring rate of opportunistic infections
Measured: At Baseline and at week 24, 48, 72, 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2010 (estimated)
- Study startJan 2013
- Primary completionDec 2015 (estimated)
- Study completionJun 2016 (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 Human Immunodeficiency VirusStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fu-Sheng Wang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Fu-Sheng Wang, Beijing 302 Hospital
- Investigators
- Fu-Sheng Wang, Professor, Principal investigator, Beijing 302 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01213186
- Sponsor's protocol ID
- beijing302-001
- Status last verified
- May 2013
- First submitted
- 28 Sep 2010
- Last updated
- 29 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008 Jan;214(2):231-41. doi: 10.1002/path.2276.
PubMed 18161758Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008 Sep;8(9):726-36. doi: 10.1038/nri2395.
PubMed 19172693Zhang Z, Fu J, Xu X, Wang S, Xu R, Zhao M, Nie W, Wang X, Zhang J, Li T, Su L, Wang FS. Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients. AIDS. 2013 May 15;27(8):1283-93. doi: 10.1097/QAD.0b013e32835fab77.
PubMed 23925377
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of UC-MSC in Restoring CD4 T Cell Counts and Reducing Immune Activation in HIV-infected Patients Underlying Long-term Antiviral Therapy: a Multicenter, Does-escalating, Randomized, Double-blind, Controlled Trial.
- ClinicalTrials.gov ID
- NCT01213186
- Acronym / sponsor ID
- beijing302-001
- Keywords
- stem cell, hiv, CD4, immune activation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Fu-Sheng WangUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 1 Oct 2010 (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.
HIV-1 infection is characterized by progressive depletion of CD4+ T cells that eventually leads to clinically significant immunodeficiency. A chronic generalized immune activation is now being recognized to be the main driving force for T cell depletion, loss of anti-HIV-1 immunity and disease progression during chronic HIV-1 infection. However, it is still unknown whether reducing immune activation will restore CD4 T cell counts and leading to immune reconstitution in chronic HIV infection. Mesenchymal stem cells (MSC) have been demonstrated to decrease immune responses of the host, and can suppress inflammation in HIV-infected non-responders. Here, the investigators propose a hypothesis that MSC can reduce immune activation which subsequently lead to the restoration of CD4 T-cell counts dependent on dose of transfused MSCs in HIV-infected patients.
Detailed description
Although HIV-1 infection is characterized by progressive depletion of CD4+ T cells that eventually leads to clinically significant immunodeficiency, a chronic generalized immune activation is now being recognized to be the main driving force for T cell depletion, loss of anti-HIV-1 immunity and disease progression during chronic HIV-1 infection. In particular, this immune activation has been identified as a disease determinant independent of viral load or cell death in HIV-1 infection. A series of clinical evidences have indicated that activated CD8 T cells may attack body cells infected with viruses. Because of this, CD4 cells infected with HIV are frequently destroyed by CD8 cells.
Mesenchymal stem cells (MSCs) are the adult stem cells originating from the mesenchymal and connective tissue of bone marrow, adipose tissue, placenta, umbilical cord, cord blood, peripheral blood, liver, etc. These cells show immunomodulation, self-renewal, and multi-directional differentiation potential. In particular, MSCs have recently emerged as promising candidates for cell-based immunotherapy because they can modulate the immune response in various ways. A series of studies have indicated that secretion of dissoluble cytokines and direct contact with MSCs can block the development and functioning of antigen-presenting cells, inhibit the differentiation of B cells, and suppress the immune response of T cells and natural killer cells. The immunosuppressive effect of infused MSCs has been successfully employed in the treatment of acute severe graft-versus-host disease (GVHD). Thus, MSC may reduce inflammatory responses and promote tissue recovery in human diseases.
The purpose of this study is to learn what dose of transfused MSC reduces the level of activation of CD8 cells in people infected with HIV. The decreased activation of CD8 cells may lead to a more CD4 T cell restoration in HIV infection. This study will also look at what dose of MSCs is tolerated and its safety in HIV- infected patients.
Participants in this study will be randomly assigned to one of three treatment arms:
Arm A:Participants will receive 48 weeks of low dose of MSC treatment followed by 48-week follow-up observation.
Arm B:Participants will receive 48 weeks of high dose of MSC treatment followed by 48-week follow-up observation.
Arm C: Participants will receive 48 weeks of saline placebo followed by 48-week follow-up observation.
Study treatment will be given at 0, 4, 12, 24, 36 and 48 week since the onset of treatment. There will be an additional 48 weeks of follow-up for purposes of safety. After treatment has started, participants will be asked to come to the clinic on Weeks 4, 12, 24, 36, 48,60,72,84 and 96. At each visit participants will receive enough study treatment to last until the next visit. Each visit will last between 2 and 3 hours. At most visits participants will have a physical exam, answer questions about any medications they are taking and how they are feeling, and have blood drawn for safety to assess CD4/CD8 cell counts and viral load. Some additional blood will also be stored for immunology testing. At some visits participants will be asked questions about their medication and medical history, have pupils dilated, have a hearing test, and have an electrocardiogram (EKG). Some visits will require participants to arrive fasting. Pregnancy tests may also be conducted if the participant is able to become pregnant or if pregnancy is suspected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Drug: high dose of MSC treatment | Experimental | Drug: high dose of MSCParticipants will receive high dose of MSC from Day 0 through the Week 48 study visit. Participants will then be followed until the Week 48 study visit. |
| low dose of MSC treatment | Experimental | Drug: low dose of MSC treatmentParticipants will receive a low dose of MSC treatment from Day 0 through the Week 48 study visit, and then follow-ed up for additional 48 weeks. |
| low dose of MSC | Placebo comparator | –Participants will receive a saline placebo treatment from Day 0 through the Week 48 study visit, and then follow-ed up for additional 48 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- HIV infected
- antiretroviral therapy (ART) for at least 24 months prior to study entry and continue within the 24 months after study entry
- CD4 count less than or equal to 250 cells/mm3 continuously and more than 50 cells/mm3 before entry and at screening, obtained within 30 days prior to study entry
- Viral load less than or equal to 50 copies/mL obtained within 30 days prior to study entry
- Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
Key exclusion criteria (7 listed)
- coinfection with other virus, including serum HCV RNA positive, or one of followings are positive in antiHAV/anti-HDV/anti-HEV plus ALT more than 80 IU/L.
- history of combination with other severe diseases including renal, circulatory, respiratory, digestive, endocrine, neural and immunological diseases and tumors.
- WBC <2.5*10E9/L, platlet counts <50*10E9/L, Hb <80g/L, lactate >2 mmol/L;
- allergic constitution;
- Accepting other immunomodulatory drugs within 6 months prior screening.
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 |
|---|---|---|
| high dose of MSCAlso: MSC treatment doseTaken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 1.5*10E6/kg for 48 weeks. | Drug | Drug: high dose of MSC treatment |
| low dose of MSC treatmentAlso: MSC low doseTaken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 0.5*10E6/kg for 48 weeks. | Drug | low dose of MSC treatment |
Primary outcome
the total CD4 T cell counts compared with CD4 T cell counts at baseline
Time frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
8 secondary outcomes
the CD38 expression on CD8 T cells
Time frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: at baseline and up to week 96
plasma RNA copies/mL
Time frame: At Entry and at Weeks 24, 48, 72, 96
the ratio of CD4 and CD8 T cells
Time frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
the HLA-DR expression on CD8 T cells
Time frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
Quality of live
Time frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96
the occurring rate of tumor
Time frame: At Baseline and at week 24, 48, 72, 96
occurring rate of opportunistic infections
Time frame: At Baseline and at week 24, 48, 72, 96
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2013.
- Background: PubMed 18161758Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008 Jan;214(2):231-41. doi: 10.1002/path.2276.
- Background: PubMed 19172693Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008 Sep;8(9):726-36. doi: 10.1038/nri2395.
- Derived from this study: PubMed 23925377Zhang Z, Fu J, Xu X, Wang S, Xu R, Zhao M, Nie W, Wang X, Zhang J, Li T, Su L, Wang FS. Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients. AIDS. 2013 May 15;27(8):1283-93. doi: 10.1097/QAD.0b013e32835fab77.
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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
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing high dose of MSC and low dose of MSC treatment in people with Human Immunodeficiency Virus and Disorder of Immune Reconstitution, run by Fu-Sheng Wang at 3 sites 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 9 inclusion and 7 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 29 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 3 sites 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 phase mean?
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 Zheng Zhang, Doctor (86-10-63879735 ext. 2015.12, zhangzheng1975@yahoo.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the total CD4 T cell counts compared with CD4 T cell counts at baseline (time frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96). 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 NCT01213186, 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 29 May 2013.