NCT01213186

Brief 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 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
72

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2013

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 28, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 1, 2010

Completed
2.3 years until next milestone

Study Start

First participant enrolled

January 1, 2013

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

May 29, 2013

Status Verified

May 1, 2013

Enrollment Period

2.9 years

First QC Date

September 28, 2010

Last Update Submit

May 26, 2013

Conditions

Human Immunodeficiency VirusDisorder of Immune Reconstitution

Keywords

stem cellhivCD4immune activation

Outcome Measures

Primary Outcomes (1)

  • the total CD4 T cell counts compared with CD4 T cell counts at baseline

    At Baseline and at week 4, 12, 24, 36,48,60,72,84,96

Secondary Outcomes (8)

  • the CD38 expression on CD8 T cells

    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

    at baseline and up to week 96

  • plasma RNA copies/mL

    At Entry and at Weeks 24, 48, 72, 96

  • the ratio of CD4 and CD8 T cells

    At Baseline and at week 4, 12, 24, 36,48,60,72,84,96

  • the HLA-DR expression on CD8 T cells

    At Baseline and at week 4, 12, 24, 36,48,60,72,84,96

  • +3 more secondary outcomes

Study Arms (3)

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.

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.

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.

Interventions

high dose of MSCDRUG

Taken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 1.5\*10E6/kg for 48 weeks.

Also known as: MSC treatment dose
Drug: high dose of MSC treatment
low dose of MSC treatmentDRUG

Taken i.v., at week 0, 4, 12, 24, 36 and 48, at a dose of 0.5\*10E6/kg for 48 weeks.

Also known as: MSC low dose
low dose of MSC treatment

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Beijing 302 Hospital

Beijing, Beijing Municipality, 100039, China

RECRUITING

Xinjiang Hospital of Infectious Diseases

Ürümqi, Xinjiang, 830013, China

RECRUITING

the Yunnan Hospital of Infectious Diseases

Kunming, Yunnan, 650301, China

RECRUITING

Related Publications (3)

  • 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.

    PMID: 18161758BACKGROUND

  • Uccelli 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.

    PMID: 19172693BACKGROUND

  • Zhang 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.

    PMID: 23925377DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Fu-Sheng Wang, Professor

    Beijing 302 Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Zheng Zhang, Doctor

CONTACT

86-10-63879735zhangzheng1975@yahoo.com.cn

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Director

Study Record Dates

First Submitted

September 28, 2010

First Posted

October 1, 2010

Study Start

January 1, 2013

Primary Completion

December 1, 2015

Study Completion

June 1, 2016

Last Updated

May 29, 2013

Record last verified: 2013-05

Locations

CN(3)