Evaluation of Vulvar Lichen Sclerosus Treatment Using Adipose Tissue Associated With Autologous Platelet-rich Plasma.

Overview

LIQUENIA clinical trial is a phase II, controlled, prospective and unicentric study to assess vulvar lichen sclerosus (VLS) treatment using adipose tissue associated with autologous platelet-rich plasma (PRP) coming from the inner side of the patients' thighs, which aims to restore the structure and elasticity of the affected vulvar subunits, and to improve vulvar subunits lesions and symptoms, therefore, patients' quality of life from the early phases of the treatment.

Full Title of Study: “Pilot Study of Vulvar Lichen Sclerosus (VLS) Treatment Using Adipose Tissue Associated With Autologous Platelet-rich Plasma (PRP).”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 12, 2019

Detailed Description

Randomized, prospective and unicentric study, in which the investigators evaluate patients with vulvar lichen sclerosus who undergo surgical treatment consisting of two separate infiltrations by intra and subdermal injection in each half vulvar of autologous fatty tissue associated with autologous platelet-rich plasma, in order to: Main objective: To estimate the population parameters of the study variables, as well as their variability, to be able to determine the sample size and statistical power for a future clinical trial whose main objective will be to demonstrate the efficacy of this treatment regarding the increase in the vulvar elasticity in patients with vulvar lichen sclerosus. Secondary Objectives: 1. To evaluate if there is a structural improvement in the vulva areas treated at month, 3 months, 6 months and 12 months after the first infiltration and at 3 and 9 months after the second infiltration. 2. To analysis the improvement of fibrosis and inflammation 6 months after the first infiltration and 3 months after the second infiltration. 3. To study if there is an improvement in symptoms at month, 3 months, 6 months, 12 months after the first infiltration and at 3 months and 9 months after the second infiltration. 4. To examine whether there is an improvement in the quality of patients life. 5. Subsequent use of clinical and pain assessment scale in this study and in another lichen sclerosus vulvar studies with a greater number of patients. 6. To evaluate the adverse events derived from the treatment during the first year after the first infiltration through its registration in the CRD.

Interventions

  • Drug: Injection of autologous fatty tissue associated with autologous platelet-rich plasma.
    • Patients will receive 2 separate infiltrations for three months by intra and subdermal injection of autologous fatty tissue (20cc) associated with autologous platelet-rich plasma (4cc) in each half vulvar.
  • Drug: Corticosteroids (clobetasol 0.05%)
    • Patients will receive a maintenance treatment of topical therapy with corticosteroids (clobetasol 0.05%) that will be administered by usual clinical practice.

Arms, Groups and Cohorts

  • Experimental: Group autologous platelet-rich plasma injection
    • Patients will receive 2 separate infiltrations for three months by intra and subdermal injection of autologous fatty tissue (20cc) associated with autologous platelet-rich plasma (4cc) in each half vulvar.
  • Active Comparator: Group Control
    • Patients will receive a maintenance treatment of topical therapy with corticosteroids (clobetasol 0.05%) that will be administered by usual clinical practice.

Clinical Trial Outcome Measures

Primary Measures

  • Vulvar elasticity measured by the cutometer-dualmpa®
    • Time Frame: Month 1 after first infiltration.
    • Vulvar elasticity will be measured by the cutometer-dualmpa® for the analysis of the elasticity improvement in the plaques of fibrosis at the affected vulvar areas.
  • Vulvar elasticity measured by the cutometer-dualmpa®
    • Time Frame: Month 3 after first infiltration.
    • Vulvar elasticity will be measured by the cutometer-dualmpa® for the analysis of the elasticity improvement in the plaques of fibrosis at the affected vulvar areas.
  • Vulvar elasticity measured by the cutometer-dualmpa®
    • Time Frame: Month 6 after first infiltration.
    • Vulvar elasticity will be measured by the cutometer-dualmpa® for the analysis of the elasticity improvement in the plaques of fibrosis at the affected vulvar areas.
  • Vulvar elasticity measured by the cutometer-dualmpa®
    • Time Frame: Year 1 after first infiltration.
    • Vulvar elasticity will be measured by the cutometer-dualmpa® for the analysis of the elasticity improvement in the plaques of fibrosis at the affected vulvar areas.
  • Vulvar elasticity measured by the cutometer-dualmpa®
    • Time Frame: Month 3 after second infiltration.
    • Vulvar elasticity will be measured by the cutometer-dualmpa® for the analysis of the elasticity improvement in the plaques of fibrosis at the affected vulvar areas.
  • Vulvar elasticity measured by the cutometer-dualmpa®
    • Time Frame: Month 9 after second infiltration.
    • Vulvar elasticity will be measured by the cutometer-dualmpa® for the analysis of the elasticity improvement in the plaques of fibrosis at the affected vulvar areas.

Secondary Measures

  • Histological improvement measured by the scale for histological assessment.
    • Time Frame: Month 6
    • The histological improvement will be determined in the treatment group by histological comparison of the biopsy samples taken pre-treatment and after 6 months of treatment, and it will be assessed by the evolution of the advanced stages (basal lamina destruction, orthokeratosis, hypergranulocytosis with an infiltrate of lymphocytes and melanophages with Civatte bodies (necrotic keratinocytes) in the papillary dermis) to earlier stages characterized by dermatitis with lymphocytic infiltrate along the epithelial junction.
  • Improvement in the quality of patients’ life measured by skindex-29 questionnaire quality of life.
    • Time Frame: Month 1, Month 3, Month 6, Year 1
    • The skindex-29 is a questionnaire designed for assessing aspects, such as degree of symptoms, psychosocial functioning, and emotional status, for assessing the effects of skin diseases on patient’s quality of life.
  • Improvement in the clinical symptoms by clinical assessment scale.
    • Time Frame: Month 1, Month 3, Month 6, Year 1
    • Clinical assessment scale is a physical examination for current status of the lesions despite treatment with topical corticosteroids. 1 point will be given to the existence of whitish plaques, 2 points to the presence of bruises, hemorrhagic blisters, erosions/ulcers, pain or bleeding during sexual intercourse and 8 points to labial adhesion (minora/major), clítoris phimosis and narrowing of the introitus. The patients with 1 point will be mild patients, the patients with 2-7 points will suffer a moderate affectation while the patients with more than 8 or + points will be in advanced stages with a serious affectation.
  • Improvement in the pruritus measured by 4D Pruritus Scale.
    • Time Frame: Month 1, Month 3, Month 6, Year 1
    • 4D Pruritus Scale is a brief but multidimensional questionnaire to assess itching. The scale scores from 0 (no negative impact) to 4 (greatest negative impact) on pruritus duration, intensity, extent and daily activities disability.
  • Improvement in the pain measured by Pain Scale.
    • Time Frame: Month 1, Month 3, Month 6, Year 1
    • The pain scale is designed for assessing pain associated with sexual intercourse and urination (2 points), resting and nightime sleep conciliation (6 points).Regarding the gradation of symptoms it will be classified as mild (1 point) the existence of mild pain/discomfort that allows normal life without taking analgesics, moderate (2-5 points) when usual doses of analgesics are required and serious with more than 5 points.
  • Improvement in sexual performance by Sexual Functioning Index (SFI)
    • Time Frame: Month 1, Month 3, Month 6, Year 1
    • Sexual Functioning Index is a questionnaire related to four topics: sexual activity, sexual intercourse, sexual stimulation and sexual desire.

Participating in This Clinical Trial

Inclusion Criteria

  • Adult women between 18 and 70 years old. – Patients with clear clinical and/or histological diagnosis of vulvar lichen sclerosus (VLS). – Moderate to severe affectation of the disease at genital level. – Patients who have taken topical treatment for at least three months with 0.05% clobetasol propionate. – Prior signed informed consent form. Exclusion Criteria:

  • Pregnant or lactating women. – Alcoholic patients. – Patients with malignant disease diagnosed in the last 5 years. – Patients infected with HSV-II, HPV, HIV, HBV and HCV viruses. – Injecting drug users. – Patients with serious active infectious diseases. – Patients with known allergy or intolerance to any of the aforementioned treatments. – Patients with inflammatory diseases that may affect the vulvar area (Crohn's disease, ulcerative colitis, psoriasis, eczema). – Patients with unrealistic expectations regarding the final benefits of the treatment.

Gender Eligibility: Female

Adult women between 18 and 70 years old

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Instituto de Investigacion Sanitaria La Fe
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Patricia Gutierrez Ontalvilla, Principal Investigator, Hospital La Fe

References

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Kreuter A, Kryvosheyeva Y, Terras S, Moritz R, Möllenhoff K, Altmeyer P, Scola N, Gambichler T. Association of autoimmune diseases with lichen sclerosus in 532 male and female patients. Acta Derm Venereol. 2013 Mar 27;93(2):238-41. doi: 10.2340/00015555-1512.

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