Treatment of Cervical Intraepithelial Neoplasia (CIN) Grade III With Non-invasive Physical Plasma

Study Overview
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Brief Summary
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The aim of the prospective, unicenter proof-of-principle study is to investigate the anti-neoplastic effectiveness of NIPP against CIN III lesions. The aim of this project is to evaluate the potential of a previous NIPP treatment to significantly reduce the invasiveness of the LEEP excision. Another aim of this study is to investigate cellular / molecular effects of NIPP following the in-vivo treatment of the cervix using molecular biological methods. For this purpose, tissue treated with plasma is taken after defined periods of time by mini biopsy and examined using molecular biological, histological and microscopic methods.

Detailed Description
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Cervical intraepithelial neoplasms (CIN), classified into severity levels CIN I to III, can be precursors to cervical cancer (CC), the world's third most common cancer in women (270,000 deaths / year), which radical therapies are often associated with lifelong severe physical and emotional stress. Cross-sectional studies found a prevalence for CIN of 62 per 1,000 women and incidences of 1.2 (CIN I), 0.8 (CIN II) and 0.7 (CIN III) per 1,000 women per year (highest incidence of CIN between 20 and 24 years) age). The standard therapy for the treatment of CIN III by LEEP excision is associated with an increase in mortality of 17%. CIN III, in particular, is associated with a significant decline in quality of life, psychological well-being and sexual health, although on average only about 12% of CIN III lesions progress to invasive CC. The resulting over-treatment (in around 8-9 out of 10 patients) with invasive procedures is a serious problem for affected women, health care providers and the health economy. The NIPP treatment is a tissue-sparing, pain-free, easy to carry out and outpatient treatment method without anesthesia and hospitalization. A non-randomized, one-arm feasibility study at the Department of Women's Health (649 / 2017BO1) already showed the effectiveness of a NIPP treatment. Clinical implications for CIN III: A previous NIPP treatment should significantly reduce the invasiveness of the LEEP excision. If the oncological safety of NIPP treatment is comparable (histological complete remission of CIN III), NIPP is to be established as a safe alternative to LEEP excision in the future.

Official Title
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Treatment of Cervical Intraepithelial Neoplasia (CIN) Grade III With Non-invasive Physical Plasma

Conditions
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Cervical Intraepithelial Neoplasia III

Intervention / Treatment
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* Procedure: Non-invasive physical plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Histologically confirmed CIN III Clearly visible transformation zone of the portio and margins of the lesions according to T1 / T2 signed written consent Exclusion Criteria: Not fully visible transformation zone Indication of an invasive disease Serious cardiovascular diseases Patients who only want to undergo a LEEP excision

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NIPP<br>Treatment of the NIPP group with physical low-temperature plasma, subsequently within 8 weeks LEEP-Exzision | Procedure: Non-invasive physical plasma<br>* Treatment with non invasive physical low-temperature plasma<br>|
| No Intervention: Controll<br>LEEP-Exzision | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of histological complete remission | Rate of histological complete remission of the CIN III at the time of the LEEP excision | 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of partial histological remission | Rate of partial histological remission of the CIN I / II | 8 Weeks | 
| Rate of decreased HPV viral load | Rate of decreased HPV viral load in tissues | 8 Weeks | 
| Pain and quality of life | Pain and quality of life (Freiburg index for patient satisfaction) Pain assessment i) previous to, ii) during, iii) 4 h after, iv) 2 days after, v) 1 week after NIPP treatment, min/max values: 0 - 10, higher scores mean worse outcome Satisfaction assessment, min/max values: 1-6, higher scores mean worse outcome | 8 Weeks |