Umbilical Cord Mesenchymal Stem Cells for Immune Reconstitution in HIV-infected Patients
Human Immunodeficiency Virus
Disorder of Immune Reconstitution
Drug: high dose of MSC
Drug: low dose of MSC treatment
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|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.|
- 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 ] [ Designated as safety issue: No ]
- the CD38 expression on CD8 T cells [ Time Frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96 ] [ Designated as safety issue: No ]
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: at baseline and up to week 96 ] [ Designated as safety issue: Yes ]
- plasma RNA copies/mL [ Time Frame: At Entry and at Weeks 24, 48, 72, 96 ] [ Designated as safety issue: No ]
- the ratio of CD4 and CD8 T cells [ Time Frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96 ] [ Designated as safety issue: No ]
- the HLA-DR expression on CD8 T cells [ Time Frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96 ] [ Designated as safety issue: No ]
- Quality of live [ Time Frame: At Baseline and at week 4, 12, 24, 36,48,60,72,84,96 ] [ Designated as safety issue: Yes ]
- the occurring rate of tumor [ Time Frame: At Baseline and at week 24, 48, 72, 96 ] [ Designated as safety issue: Yes ]
- occurring rate of opportunistic infections [ Time Frame: At Baseline and at week 24, 48, 72, 96 ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Drug: high dose of MSC treatment
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.
Drug: high dose of MSC
Taken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 1.5*10E6/kg for 48 weeks.
Other Name: MSC treatment dose
Experimental: low dose of MSC treatment
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.
Drug: low dose of MSC treatment
Taken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 0.5*10E6/kg for 48 weeks.
Other Name: MSC low dose
Placebo Comparator: low dose of MSC
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01213186
|Contact: Zheng Zhang, Doctor||86-10-63879735 ext firstname.lastname@example.org|
|Beijing 302 Hospital||Recruiting|
|Beijing, Beijing, China, 100039|
|Contact: Zheng Zhang, Doctor 86-10-63879735 ext 2015.12 email@example.com|
|Principal Investigator: Fu-Sheng Wang, Professor|
|Xinjiang Hospital of Infectious Diseases||Recruiting|
|Urumqi, Xinjiang, China, 830013|
|Contact: Xiuling Wang, Professor 0991-6665288 firstname.lastname@example.org|
|Principal Investigator: Hao Wu, Professor|
|the Yunnan Hospital of Infectious Diseases||Recruiting|
|Kunming, Yunnan, China, 650301|
|Contact: Xicheng Wang, Doctor 86-0871-6256092 ext 2015.12 email@example.com|
|Sub-Investigator: Xicheng Wang, doctor|
|Principal Investigator:||Fu-Sheng Wang, Professor||Beijing 302 Hospital|