Depth of Necrosis in Normal Cervical Epithelium After 85% Trichloroacetic Acid (TCA) Application

NCT04911075 | Completed DMC

• 1 other identifier: 21020134
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Early detection and treatment of precancerous lesions are the pillars of cervical cancer prevention. Cervical Intraepithelial Neoplasia (CIN) is a precancerous lesion that histologically can be found in one of three stages of development; CIN-I (low grade), CIN-II, or CIN-III (collectively called high grade), depending on the proportion of the depth of the lesion to the thickness of the cervical epithelium. The higher the degree of CIN, the deeper the pre-cancerous lesions are found in the epithelial lining of the cervix. Therefore, from the point of view of precancerous lesions treatment, its effectiveness will be determined by the ability to eradicate all high-grade lesions. In other words, it has an effect that can reach depths beyond the depth of the high grade lesion. According to a study in the US (1982), as many as 99.7% of CIN-III cases had a lesion depth of less than 4.8 millimeter. Furthermore, a Netherlands study (1990) stated that as many as 99.7% of CIN-III cases had a maximum lesion depth of 3.6 millimeters. While in subjects from developing countries, study from Peru (2018) showed that 93.5% of CIN-III cases have a lesion depth of less than 5 millimeters. Based on the results of these studies, a treatment for CIN can only be said to be effective if it can create a therapeutic effect which can reach depths of 4-5 millimeters in cervix epithelial. Trichloroacetic acid (TCA) is an acetic acid analogue, which has long been known as a chemical peel and also frequently used to treat genital ward and precancerous skin lesions. The effect of TCA therapy is the destruction of the epithelium forming epithelial necrosis, followed by re-epithelialization of the supporting tissue and stimulation of collagen synthesis within approximately in 24 hours. There are no studies regarding the depth of cervical necrosis that can be achieved by application of this solution to the cervix epithelial.

Conditions

Cervix; Intraepithelial Neoplasia

Keywords

Trichloroacetic Acid (TCA); Depth of Necrosis; Cervix Intraepithelial Neoplasia

Outcome Measures

Primary Outcomes (1)

• Depth of Cervical Epithelial Ablation

  Based on damage to the cervical epithelium, both squamous (ectocervix), transformation zone, and columnar (endocervix) epithelium. Destruction of base membrane and stromal tissue will also be evaluated. Microscopic evaluation using a micrometer on a 10 times magnification eyepiece. The deepest ablative destruction in epithelial, base membrane, and stromal tissue will be recorded and stated in millimetres.

  30 days

Secondary Outcomes (1)

• Pain Scores

  10 minutes

Study Arms (1)

85% TCA Group

EXPERIMENTAL

* Participants are subject who will undergo an elective total hysterectomy procedure for indications of gynecological organ abnormalities, whether benign, pre-cancerous, or malignant other than cervical pathology. * The 85 percent TCA solution will be applied to participants cervical tissue 24 hours before surgery.

Drug: 85% TCA Solution

Interventions

85% TCA Solution DRUG

* TCA is an acetic acid analogue solution (CCl3COOH) which is formed from the reaction of acetic acid (CH3COOH) with chlorine (3Cl2). * High concentrations (85 percent) of this solution can penetrate deeply into the epidermis-dermis layer and cause cells necrosis. * This solution (1-2 milliliter) will be applied to participants cervical tissue (ectocervix and endocervix) using cotton swab for 1-3 minutes.

Also known as: CCl₃COOH

85% TCA Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Normal cervix without significant changes and must be tested negative for Visual Inspection Acetic-Acid (VIA) test (no acetowhite lesions are found)
• Participants are willing to participate voluntarily in this research by signing a consent form.

You may not qualify if:

• Patients who finally have undergone sub-total or supra-vaginal hysterectomy.
• Any abnormalities found in postoperative cervical histopathology results.

Sponsors & Collaborators

• Indonesia University: lead
• Dr Cipto Mangunkusumo General Hospital: collaborator

Study Sites (1)

dr. Cipto Mangunkusumo National Central General Hospital

Jakarta, 10430, Indonesia

Location

Related Publications (8)

• Boonstra H, Aalders JG, Koudstaal J, Oosterhuis JW, Janssens J. Minimum extension and appropriate topographic position of tissue destruction for treatment of cervical intraepithelial neoplasia. Obstet Gynecol. 1990 Feb;75(2):227-31.

  PMID: 2300349 BACKGROUND

• Abdul-Karim FW, Fu YS, Reagan JW, Wentz WB. Morphometric study of intraepithelial neoplasia of the uterine cervix. Obstet Gynecol. 1982 Aug;60(2):210-4.

  PMID: 7155483 BACKGROUND

• Taxa L, Jeronimo J, Alonzo TA, Gage J, Castle PE, Cremer ML, Felix JC. Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis. J Low Genit Tract Dis. 2018 Jan;22(1):27-30. doi: 10.1097/LGT.0000000000000355.

  PMID: 29271853 BACKGROUND

• Brodland DG, Cullimore KC, Roenigk RK, Gibson LE. Depths of chemexfoliation induced by various concentrations and application techniques of trichloroacetic acid in a porcine model. J Dermatol Surg Oncol. 1989 Sep;15(9):967-71. doi: 10.1111/j.1524-4725.1989.tb03183.x.

  PMID: 2778185 BACKGROUND

• Mariategui J, Santos C, Taxa L, Jeronimo J, Castle PE. Comparison of depth of necrosis achieved by CO2- and N2O-cryotherapy. Int J Gynaecol Obstet. 2008 Jan;100(1):24-6. doi: 10.1016/j.ijgo.2007.07.009. Epub 2007 Sep 25.

  PMID: 17897647 BACKGROUND

• Adepiti AC, Ajenifuja OK, Fadahunsi OO, Osasan SA, Pelemo OE, Loto MO. Comparison of the depth of tissue necrosis between double-freeze and single-freeze nitrous oxide-based cryotherapy. Niger Med J. 2016 Jan-Feb;57(1):1-4. doi: 10.4103/0300-1652.180561.

  PMID: 27185971 BACKGROUND

• Geisler S, Speiser S, Speiser L, Heinze G, Rosenthal A, Speiser P. Short-Term Efficacy of Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia. Obstet Gynecol. 2016 Feb;127(2):353-9. doi: 10.1097/AOG.0000000000001244.

  PMID: 26942365 BACKGROUND

• Walker DC, Brown BH, Blackett AD, Tidy J, Smallwood RH. A study of the morphological parameters of cervical squamous epithelium. Physiol Meas. 2003 Feb;24(1):121-35. doi: 10.1088/0967-3334/24/1/309.

  PMID: 12636191 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Laila Nuranna, Professor

  Indonesia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 2, 2021
• Study Start: April 15, 2021
• Primary Completion: October 25, 2021
• Study Completion: October 25, 2021
• Last Updated: December 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD will become available 1 year after publication for duration of 1 year
• Access Criteria: IPD will be shared with investigators from Indonesia and any additional supporting information will be shared, including with whom, for what types of analyses, and by what mechanism. Information about who will review requests and criteria for reviewing requests may also be provided.

Locations

ID (1)