Clinical trial NCT05872659: Mesenchymal Stem Cells for Immune Non-responder Patients With HIV Infection
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: AIDS Virus
Disorder of Immune Reconstitution
Keywords: HIV
mesenchymal stem cell
Immune Non-responder
CD4
AIDS
Immune reconstitution
Lead sponsor: Shandong Qilu Cell Therapy Engineering Technology Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Shandong Public Health Clinical Center
First posted: 2023-05-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in CD4+T cell counts
timeFrame: Change from Baseline at 12 months
Secondary outcomes:
measure: change in CD4/CD8
timeFrame: Change from Baseline at 12 months
measure: change in RNA viral load
timeFrame: Change from Baseline at 12 months
measure: The incidence of opportunistic infections
timeFrame: 12 months
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Public Health Clinical Center
state: Shandong
Study officials:
affiliation: Shandong Public Health Clinical Center
name: Chenfan liu
role: PRINCIPAL_INVESTIGATOR
References: