Mesenchymal Stem Cells for Immune Non-responder Patients With HIV Infection

A Clinical Study to Evaluate the Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cells Combined With Antiviral Therapy in the Treatment of AIDS Patients With Immune Non-responder

The goal of this clinical trial is to explore the effect of mesenchymal stem cell therapy on immune non-responder patients. The main questions it aims to answer are:

1. Efficacy of human umbilical cord mesenchymal stem cells combined with antiviral therapy in the treatment of AIDS patients with immune non-response.
2. Safety of human umbilical cord mesenchymal stem cells combined with antiviral therapy in AIDS patients with immune non-response.

Participants will receive CD4,CD4/CD8, and RNA viral load tests and will be randomly assigned to either saline or mesenchymal stem cell therapy.

Investigators will evaluate the safety and efficacy of mesenchymal stem cell therapy based on examination results.

Study Overview

• Status: Recruiting
• Conditions: AIDS Virus; Disorder of Immune Reconstitution
• Intervention / Treatment: Other: normal saline; Biological: Mesenchymal stem cells

Detailed Description

Highly active antiretroviral therapy (HAART) is an effective means to inhibit virus replication, increase the number of CD4+T lymphocytes and reduce mortality in HIV-infected people. However, it has been found that around 10% - 40% of patients have not achieved ideal immune function reconstruction under the condition of good viral load control and are referred to as"inadequate immunological responders" or "immune non-responders" (INRs).

A series of intervention measures have been proposed for patients with immune non-response, including growth hormone therapy, immunosuppressive therapy, cytokine therapy, traditional Chinese medicine therapy, etc., but there is no specific and effective treatment in clinical practice.

Mesenchymal stem cells (MSCs) are pluripotent stem cells with high self-renewal ability and multi-directional differentiation potential derived from mesoderm. MSCs have considerable therapeutic effects due to their migration, differentiation, immune-modulation, and regeneration abilities. The immunomodulatory effect of mesenchymal stem cells can inhibit the excessive immune activation in patients. At the same time, the paracrine effect of mesenchymal stem cells can also regulate the disordered microenvironment and promote the repair of damaged cells and tissues.

This is a randomised, placebo-controlled, clinical trial to evaluate the safety and feasibility of a 3-doses treatment regimen with MSCs (1 million cells/Kg MSCs, months 0-1-2) in HIV infected adults with immune non-response. Subjects are block randomised (1:1) to receive either MSCs (n=10), or placebo (n=10), as the control treatment. Changes in CD4+Tcount and CD4/8，adverse events, opportunistic infection signs are evaluated as determinants of safety and efficacy of MSCs. Study endpoints are measured along a follow-up period of 12 months, that includes 7 visits.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Chenfan Liu; Phone Number: 17862958810; Email: 1780966676@qq.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Public Health Clinical Center
      • Contact: Chenfan Liu; Phone Number: 17862958810; Email: 1780966676@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed HIV infection.
• ≥18 years old, gender unlimited.
• ≥12 months of continuous antiviral therapy and at least 2 viral loads (3 months or more apart) < 50 Copies/mL at screening.
• The antiviral regimen was not changed in the 12 months prior to enrollment.
• CD4+T lymphocyte count < 200 μL-1 in patients receiving antiviral therapy for more than 1 year and less than 2 years or < 350 μL-1 in patients receiving antiviral therapy for ≥ 2 years.
• Understand and sign the informed consent.

Exclusion Criteria:

• Infection with other viruses: HBV-DNA positive, HCV RNA positive, anti-Hav IgM, anti-HDV IgM and anti-HEV IgM positive and ALT >80 IU/L, anti-TP positive.
• Active and uncontrollable infection.
• Malignant tumor or tumor history.
• Complicated with abnormal function of heart, liver, lung, kidney and other major organs.
• When the laboratory test satisfies any item (WBC < 3.5*10^9/L; PLT < 80*10^9/L; HGB < 100 g/L).
• Drug dependent.
• Pregnant and lactating women.
• Severe allergic constitution, or known allergy to the study drug and its components;
• Accepting immunosuppressants or other immunomodulators (including thymosin) or systemic cytotoxic agents within 6 months prior to screening.
• Participated in other clinical studies within 3 months prior to this study.
• patients with any condition which the investigator or treating physician feels would interfere with the trial or the safety of the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; Participants will receive continuous antiviral therapy and saline placebo (iv, 100 mL) treatment on Day 0，Day30，Day60 and followed up for 48 weeks.	Other: normal saline; iv at D0, D30, D60
Experimental: Treatment group; Participants will receive continuous antiviral therapy and Mesenchymal stem cells (1*10^6/kg subject weight, iv, 100 mL) treatment on Day 0，Day30，Day60 and followed up for 48 weeks.	Biological: Mesenchymal stem cells; iv at D0, D30, D60

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD4+T cell counts	the total CD4+T cell counts compared with CD4 T cell counts at baseline	Change from Baseline at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in CD4/CD8	the value of CD4/CD8 compared with CD4/CD8 value at baseline	Change from Baseline at 12 months
change in RNA viral load	the RNA viral load compared with RNA viral load at baseline	Change from Baseline at 12 months
The incidence of opportunistic infections	Incidence of opportunistic infections throughout the study period	12 months

Collaborators and Investigators

• Sponsor: Shandong Qilu Cell Therapy Engineering Technology Co., Ltd
• Collaborators: Shandong Public Health Clinical Center
• Investigators: Principal Investigator: Chenfan liu, Shandong Public Health Clinical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2023
• Primary Completion (Anticipated): November 15, 2025
• Study Completion (Anticipated): November 15, 2025

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: May 14, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: HIV; AIDS; mesenchymal stem cell; CD4; Immune reconstitution; Immune Non-responder
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: MSCT-A-22

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No