The development of technologies increasing diagnosis and treatment efficiency of the cervix diseases associated with human papillomavirus (HPV)
| ISRCTN | ISRCTN10428760 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10428760 |
- Submission date
- 03/07/2023
- Registration date
- 11/07/2023
- Last edited
- 11/07/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Cervical cancer (CC) is a common type of cancer affecting the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precancerous condition that can lead to CC. Women with CIN have a 20 times higher risk of developing CC compared to healthy women. It is crucial to treat CIN in its early stages to prevent its progression to invasive CC.
Human papillomavirus (HPV) is a group of viruses that are widespread worldwide. Oncogenic HPV can persist in the body and evade the immune system, leading to sequential carcinogenesis from infection to invasive cancer. HPV infection is detected in over 99.7% of CC cases and is considered the main risk factor for CIN.
Traditional treatments for CC include surgery, radiation, and chemotherapy, but these methods can have side effects and impact fertility. Therefore, there is a need for effective alternative treatments for CIN and cervical HPV that do not compromise fertility.
Photodynamic therapy (PDT) is a promising approach to prevent the recurrence of HPV-associated cervical lesions. PDT involves using photosensitizers (PS), which accumulate in affected tissue. When these PS interact with light of a specific wavelength, they initiate photophysical processes that damage or destroy the affected area. PDT consists of two stages: administering the PS and directing local light irradiation. The success of PDT depends on oxygen-induced activation of the PS, proper use of visible light, and the appropriate choice of PS. These factors lead to the formation of free radicals, such as singlet oxygen, which cause local photooxidation, cell damage, and destruction.
To enhance the effectiveness of HPV-associated infection treatment, a combination of local PDT and systemic photosensitivity during intravenous laser blood irradiation (SPILBI) is proposed. This program aims to develop an innovative technology that improves the diagnosis and treatment of background and precancerous cervical lesions associated with HPV.
The research hypothesis will test the cumulative effect of three components of laser technology with photosensitivity: fluorescent diagnostics using PS, evaluation of PS "burnout" during local PDT, and SPILBI. Genetic and immunological features of the innate immune response, along with viral and bacterial load indicators, liquid cytology, and immunocytochemical assessment, will be considered to personalize the approach to PDT based on the heterogeneity of the disease.
Who can participate?
Adult women aged 18 - 45 years with CIN and HPV
What does the study involve?
The main group will undergo local and systemic PDT without antiviral therapy. The control group will undergo antiviral therapy using geneferon and valaciclovir but without PDT.
What are the possible benefits and risks of participating?
Potential inconveniences and risks associated with the study do not exceed the inconveniences and risks during PDT and the administered physiological dose of the Photolon photosensitizer. Participation in a study may require longer and more frequent visits to the doctor than regular appointments. Control examinations after photodynamic therapy will be carried out after 1, 3, 6 and 12 months. In case of poor-quality performance, the risks are as follows: during PDT, pain of varying severity (from a burning sensation to sharp pains) in the irradiation area is possible and can persist from several hours to 1 day, fever is rarely observed to subfebrile figures on the 2nd day after the procedure, which may be a consequence of the development of aseptic inflammation after intracavitary PDT. Allergic reactions are possible. Within 1-2 months after the administration of PS, phototoxic skin reactions are possible when exposed to sunlight. With an increase in temperature to subfebrile figures, a transient increase in blood pressure, special treatment is not required, and activities continue in accordance with the developed program. In general, the complication rate does not exceed 5%.
Where is the study run from?
Ministry of Science and Higher Education of the Republic of Kazakhstan
When is the study starting and how long is it expected to run for?
August 2022 to August 2024
Who is funding the study?
Ministry of Science and Higher Education of the Republic of Kazakhstan
Who is the main contact?
Shanazarov Nasrulla Abdullayevich, Shanazarov@bmc.mcudp.kz
Contact information
Principal Investigator
80, Mangilik El
Astana
010000
Kazakhstan
 ORCID ID |
0000-0002-2976-259X |
|---|---|
| Phone | +7 7172 708081 |
| Shanazarov@bmc.mcudp.kz |
Study information
| Study design | Single-center interventional non-randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Diagnostic, Treatment |
| Participant information sheet | 43885_PIS_Kazakh.pdf |
| Scientific title | The development of innovative technologies increasing diagnosis and treatment efficiency of the cervix background and precancerous diseases associated with HPV |
| Study acronym | PDT-HPV |
| Study objectives | The effectiveness and safety of using a combination of local and systemic photodynamic therapy (PDT) for the diagnosis and treatment of the Human Papilloma Virus (HPV)-associated Cervical intraepithelial neoplasia (CIN) in Kazakh women of reproductive age, taking into account their genotypic and immunological characteristics. |
| Ethics approval(s) |
Approved 09/08/2022, Local Commission on Bioethics of the Medical Center Hospital of the President’s Affairs Administration of the Republic of Kazakhstan (80, Mangilik El Street, Astana, 010000, Kazakhstan; +7 87172708102; sibagatova@bmc.mcudp.kz), ref: Avdeyev@bmc.mcudp.kz |
| Health condition(s) or problem(s) studied | HPV-associated cervical intraepithelial neoplasia |
| Intervention | The study aims to recruit two cohorts of patients with established HPV and cervical intraepithelial neoplasia (CIN). The main group will consist of 150 participants from the hospital, who will undergo local and systemic photodynamic therapy (PDT) without antiviral therapy. The control group will include 50 women who will undergo antiviral therapy using geneferon and valaciclovir, but without PDT. The procedure begins by administering the photosensitizer "Photolon" intravenously after dilution with saline. After 2-3 hours, the systemic photosensitivity during intravenous laser blood irradiation (SPILBI) procedure is performed. This involves irradiating the blood with light through an optical fiber inserted into a vein using the LAMI-Helios laser device from Russia. The SPILBI procedure lasts approximately 30-50 minutes. The photosensitizer accumulates in tumor tissue more than healthy tissues and organs, and when irradiated with light, it induces a photochemical reaction that destroys the cancer cells. Following the SPILBI procedure, a local PDT is performed. The patient is positioned on a gynecological chair, and under the guidance of a colposcope, fluorescent diagnostics is performed to identify all the pathological areas of the cervical epithelium accurately. Special light guides and thin diffusers are used to deliver light from a laser with a wavelength between 395-405 nm to the affected epithelium. This makes the pathological areas visible and accessible for PDT. |
| Intervention type | Mixed |
| Primary outcome measure | 1. Differential detection and quantitative determination of HPV, as well as a test for ureaplasmosis, mycoplasmosis, candidiasis are performed using the Real-time CFX96 Touch amplifier (USA) 3, 6, 12 months after PDT |
| Secondary outcome measures | 1. Full blood count is measured using the hematology analyzer Sysmex XN-3000 (Japan) at the 5th day and 3, 6, 12 months after PDT. 2. CD3, CD4, CD8, CD19, CD16, CD 56 are measured using the flow cytometer BD FACSCanto II Becton Dickinson (USA) at the 5th day and 3, 6, 12 months after PDT. 3. Interleukin 1, interleukin 6, and tumor necrosis factor are measured using the enzyme immunoassay at the Freedom EVOlyzer (Tecan, Austria) at the 5th day and 3, 6, 12 months after PDT. 4. To determine сervical intraepithelial neoplasia (CIN) colposcopy is performed 3, 6, 12 months after PDT. |
| Overall study start date | 09/08/2022 |
| Completion date | 10/08/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Female |
| Target number of participants | 200 |
| Key inclusion criteria | 1. Female 2. Age 18 - 45 years old 3. Established diagnosis of CIN 4. Positive PCR result for HPV 5. Lack of surgical treatment of CIN / absence of conization of the cervix 6. Kazakh nationality |
| Key exclusion criteria | 1. Male 2. Age under 18 and over 45 years 3. Surgical treatment of CIN / conization of the cervix 4. Persons mentally or legally incompetent, which prevents obtaining informed consent 5. Pregnant or lactating women 6. Acute gonococcal and non-gonococcal infections of the urethra and lower reproductive tract 7. Severe and decompensated diseases of the liver and kidneys, cardiovascular system 8. Autoimmune diseases 9. Oncological diseases 10. Porphyria and other photoallergic conditions 11. Taking anticoagulants |
| Date of first enrolment | 03/03/2023 |
| Date of final enrolment | 30/09/2023 |
Locations
Countries of recruitment
- Kazakhstan
Study participating centre
Astana
010000
Kazakhstan
Sponsor information
Government
8, Mangilik El
Astana
010000
Kazakhstan
| Phone | +7 7172 74-19-42 |
|---|---|
| kense@sci.gov.kz | |
| Website | https://www.gov.kz/memleket/entities/sci?lang=en |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The results obtained during the study will also be presented by 3 publications in peer-reviewed scientific journals, indexed in the Science Citation Index Expanded of the Web of Science database and (or) having a CiteScore percentile in the Scopus database of at least 35, abstracts and 2 reports at international conferences, as well as 3 articles in a publication recommended by the Committee for Quality Assurance in the Sphere of Education and Science of the Ministry of Education and Science of the Republic of Kazakhstan. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from Shanazarov Nasrulla Abdullayevich (Shanazarov@bmc.mcudp.kz) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 05/07/2023 | No | Yes | ||
| Participant information sheet | 05/07/2023 | No | Yes | ||
| Participant information sheet | 05/07/2023 | No | Yes |
Additional files
Editorial Notes
05/07/2023: Study's existence confirmed by the Local Commission on Bioethics of the Medical Center Hospital of the President’s Affairs Administration of the Republic of Kazakhstan.
