HUC-MSC for Treatment of High-risk HPV Infection

Official title

Effectiveness and Safety of Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of HPV High-risk Infection

Overview

To evaluate the safety and initial effectiveness of human umbilical cord mesenchymal stem cells in HPV clearance.

Detailed description

Cervical cancer is one of the most common malignant tumors of the female reproductive system with the highest incidence. Nearly 99.7% of cervical cancer is caused by HPV infection. Studies have shown that the persistent infection of high-risk human papillomavirus (HR-HPV) is an independent risk factor for cervical cancer which can lead to a 250-fold increased risk of high-grade cervical intraepithelial neoplasia (CIN). In patients with persistent HR-HPV infection for more than 12 months, the risk of diagnosis of high-grade squamous intraepithelial lesions of the cervix by 30 months increased to 21%. In the process of progression from HPV infection to cervical cancer, cervical precancerous lesions, namely intraepithelial neoplasia (CIN), will be experienced. Therefore, effective control of HPV infection, especially the elimination of persistent HR-HPV infection, will greatly reduce the incidence of CIN and cervical cancer. It is an urgent clinical need to actively intervene in patients with persistent infections for more than one year with a clinical significance at present.

Mesenchymal Stem Cells (MSCs) are a class of pluripotent stem cells derived from the mesoderm and ectoderm of early development, which can be easily obtained from a variety of tissue organs, having a strong proliferation and multidirectional differentiation potential in vitro. hUC-MSCs have a great effect on immune regulation and anti-inflammatory properties with a fewer ethical, availability, safety issues and a broader prospect in clinical research and application. At present, many experimental data have proved that MSCs can enhance the clearance of virus by immune cells in vivo, and have a certain application prospect in fighting virus infection. The purpose of this study was to evaluate the safety and therapeutic efficacy of human umbilical cord mesenchymal stem cells (HUC-MSCs) in clearing HPV infection, and to provide clinical basis for HUC-MSCs to clear HPV infection.

Interventions

• Biological hUC-MSCs
  1×10\^6/Kg hUC-MSCs (suspended in 100 mL normal saline containing 5% albumin) are infused intravenously to patients at a controlled rate of 60-80 drops/min.
• Biological Saline+albumin
  Normal saline containing 5% albumin had a similar suspension and appearance package to hUC-MSCs, but no MSCs

Primary outcome measures

• Adverse events-The incidence rate of allergic reaction [Time frame: 1day,1st,4th,12th,and 36th week]
• The 24 type HPV viral load [Time frame: -28th~0day,4th,12th,and 36th week]

Secondary outcome measures (10)

• The percentage of CD3+ [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The percentage of CD4+ [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The percentage of CD8+ [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The percentage of CD19+ [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The percentage of CD16+/CD56+ [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The serum level of IFN-γ [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The serum level of IL-6 [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The serum level of IL-8 [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The serum level of IL-10 [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]
• The serum level of TNF-α [Time frame: -28th~0day,1day,1st,4th,12th,and 36th week]

Eligibility criteria

Inclusion criteria

• Women aged 25-60 with a sexual history of more than 2 years;
• Confirmed HPV infection by HPV-24 test;Patients diagnosed with high-risk human papillomavirus (HR-HPV) persistent infection; (note: the HR HPV: HPV 16/18/31/33/35/39/45/51/52/53/56/58/59/66/68; 15 types)
• The subjects were not participating in other clinical trials at the same time, and had no other anti-HPV drugs or intervention therapy recently;
• If the pregnancy test is negative and the subjects have fertility potential, they agree to use effective contraception during the study period and within 6 months of completion or termination of the study;
• Voluntarily participate in and agree to cooperate in accordance with the requirements of the program, and sign the informed consent.

Exclusion criteria

• Women who are preparing for pregnancy, pregnancy or breastfeeding;
• Pathological diagnosis of high-grade squamous intraepithelial lesion (HSIL) or cervical cancer;
• Previous HPV vaccinations;
• A history of severe drug allergies, or allergies to stem cell products or other biologics;
• Previous cervical site physical therapy or related surgical history;
• Patients with severe immune dysfunction (such as AIDS, systemic lupus erythematosus and other immune system diseases or history of organ transplantation, malignant tumor chemotherapy history), serious cardiovascular, liver, kidney, nervous, hematopoietic system diseases or malignant tumors, or mental diseases;
• Recent use of other antiviral drugs, immunosuppressants, immunomodulators or steroid hormones that affect the immune system;
• Patients with acute genital tract inflammation or pelvic inflammation;
• Those who have participated in or are participating in clinical trials of other drugs within three months;
• Other conditions considered inappropriate by the investigator for inclusion in this clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Shanghai East Hospital, Tongji University School of Medicine — Shanghai

Identifiers

NCT: NCT06610773 · DFSC-2024(CR)-001 · HX-2021-007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗