A Exploratory Study of Vγ2Vδ2 T Lymphocyte-based Immunotherapy for MDR-TB

August 8, 2022 updated by: Wei Sha MD & PhD, Shanghai Pulmonary Hospital, Shanghai, China
A Exploratory Study of drug combination (zoledronic acid/interleukin 2) that specifically amplifies Vγ2Vδ2 T cells in combination with anti-tuberculosis chemotherapy for the treatment of MDR-TB.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The emergence and prevalence of drug-resistant TB in recent years has made TB control more challenging, and MDR-TB is more serious type of drug-resistance TB with a cure rate of just over half, even with the latest treatment regimens. Treatment modalities other than drugs should be considered for patients with drug-resistant TB who have poor treatment efficacy, for patients with drug-resistant TB who are unresponsive to treatment, and for other patients for whom an effective treatment regimen cannot be composed.

The human immune system plays an important role in the infection, development, treatment and regression of tuberculosis.Mtb is an intracellularly parasitic bacterium that evades host immune clearance.Immunotherapy for TB can kill intracellularly parasitic Mycobacterium tuberculosis, including drug-resistant Mycobacterium tuberculosis, by inducing a host-specific immune response.The combination of antituberculosis chemotherapy and immunotherapy has the potential to open up new avenues for the treatment of multidrug-resistant TB.

In recent years, several studies by our team and others addressing host immune mechanisms have shown that γδ T cells play an important role in the fight against TB infection.Vγ2Vδ2 T cells (also known as Vγ9Vδ2 T cells) are a specific subset of γδ T cells, the only γδ T cells capable of recognizing TB phosphoantigens, and are found only in human and non-human primates.

Our previous study demonstrated that zoledronic acid, an anti-osteoporotic and osteoprotective drug, induced the production of endogenous ligands for Vγ2Vδ2T cells and activated Vγ2Vδ2T cells. Zoledronic acid in combination with interleukin 2 can significantly expand Vγ2Vδ2T cells, and the expanded Vγ2Vδ2T cells can effectively kill intracellular parasitic Mycobacterium tuberculosis, it can also promote the production of more anti-tuberculosis effectors by Vγ2Vδ2T cells and widely stimulate the production of functional cytokines by CD4 and CD8 T cells.

The primate experiments conducted by our team in the ABSL-III laboratory of Wuhan University demonstrated that phosphoantigen/interleukin 2 in a macaque model of tuberculosis infection induced lung phosphoantigen-specific Vγ2Vδ2 T cell expansion and migration, reduced Mycobacterium tuberculosis load in vivo, and effectively improved immune resistance to tuberculosis lung necrosis, demonstrating that targeted Vγ2Vδ2 T cell Immunotherapy of Vγ2Vδ2 T cells has a significant therapeutic effect on TB infection in monkeys , and is also safe for use in macaques. Accordingly, the investigators propose a drug combination (zoledronic acid/interleukin 2) that specifically amplifies Vγ2Vδ2 T cells in combination with anti-tuberculosis chemotherapy for the treatment of multidrug-resistant tuberculosis.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Shanghai Pulmonary Hospital
      • Shanghai, China, 200433
        • Recruiting
        • Shanghai Pulmonary Hospital, Shanghai, China
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • RR-TB/MDR-TB (resistant to at least isoniazid and rifampicin).
  • Poor efficacy of the original treatment regimen or no response to treatment or less than 4 effective drugs.

Exclusion Criteria:

  • Immunosuppression due to co-morbidities, such as immune system disorders, tumors, etc.
  • Test confirms poor response to ZOL and IL-2 stimulation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vγ2Vδ2 T lymphocyte-based immunotherapy +Treatment regimens for MDR-TB
Treatment was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis, with the addition of immunotherapy：zoledronic acid and recombinant human interleukin 2
Drug: Vγ2Vδ2 T lymphocyte-based immunotherapy
Intravenous injection of zoledronic acid, followed by a subcutaneous injection recombinant human interleukin. Zoledronic acid was administered 3 times and recombinant human interleukin was administered 10 times for a total of 6 months.
Other Names:
  • Drug combination (zoledronic acid/interleukin 2)
Drug: Treatment regimens for MDR-TB
Treatment regimens was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis.
Other Names:
  • Treatment regimen for MDR-TB using WHO guidelines
Active Comparator: Treatment regimens for MDR-TB
Treatment regimens was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis.
Drug: Treatment regimens for MDR-TB
Treatment regimens was based on the principles of the WHO guidelines for the treatment of drug-resistant tuberculosis.
Other Names:
  • Treatment regimen for MDR-TB using WHO guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sputum smear and culture negative conversion
Time Frame: Through study completion, an average of 24 months.
Sputum smear microscopy, bacterial culture. Bacterial culture was performed via a mycobacterial growth indicator tube (MGIT) using the BACTEC MGIT 960 system.
Through study completion, an average of 24 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic changes
Time Frame: Through study completion, an average of 24 months.
Radiographic changes after treatment compared to baseline.Outcomes were defined as unchanged or deteriorated; ecovered; improved based on radiological findings compared to baseline.
Through study completion, an average of 24 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment outcome
Time Frame: Through study completion, an average of 24 months.
Treatment outcome assessed at the end of the treatment course according to the new definitions released by the WHO.Classified as Treatment success (cure, treatment completion); Treatment failure, Death, Loss, Inconclusive.
Through study completion, an average of 24 months.
Adverse reactions
Time Frame: Through study completion, an average of 24 months.
Adverse reactions to drugs: Number of patients with Grade 3 or 4 Adverse Events，using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting
Through study completion, an average of 24 months.
Immunological indicators
Time Frame: Through study completion, an average of 24 months.
The ability of Vγ2Vδ2 T cells to produce functional cytokines was analyzed. The results were enhanced/reduced cytokine production.
Through study completion, an average of 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Pulmonary Hospital, Shanghai, China

Collaborators

Huashan Hospital
Shanghai Public Health Clinical Center
No.85 Hospital, Changning, Shanghai, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 3, 2022

Primary Completion (Anticipated)

August 3, 2025

Study Completion (Anticipated)

August 3, 2027

Study Registration Dates

First Submitted

August 3, 2022

First Submitted That Met QC Criteria

August 5, 2022

First Posted (Actual)

August 9, 2022

Study Record Updates

Last Update Posted (Actual)

August 10, 2022

Last Update Submitted That Met QC Criteria

August 8, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • L20-209

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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