Efficacy of the Use of Cellular Matrix/ A-CP-HA Kit (CellularMatrix)

The Efficacy of the Use of Cellular Matrix / A-CP-HA Kit (Combination of Autologous Platelet-rich Plasma and Non-cross-linked Hyaluronic Acid) Compared to Local Estrogen Therapy (Blissel, Estriol 50 Micrograms/g Vaginal Gel) in Women With Genitourinary Syndrome of Menopause. A Randomized Controlled Trial, With a Second Blind Observer.

This study is a randomized, controlled, non-inferiority trial, that will be performed on 192 women on Menopause (absence of menstruation for at least 12 months), with diagnostic of genitourinary syndrome of menopause (SGM) and a vaginal health index <15 points, that are sexually active.

Patients will be randomized 1:1, equal number assigned to each of the two treatment groups, to receive treatment with two dose of Cellular Matrix / A-CP-HA Kit (a combination of autologous platelet-rich plasma and non-cross-linked hyaluronic acid) separated for a month, and control group that will receive the standard treatment for SGM, local estrogen therapy (Blissel, estriol 50 micrograms/g vaginal gel).

Both groups will be follow-up for 3 and 6 month afther treatment, a blind observer will assess the application of the validated scale (VHIS, VHI), and the investigators will do the FSD, symptom record, maturation index, follow-up photography and evaluation of adverse events and treatment compliance and adherence.

Study Overview

• Status: Recruiting
• Conditions: Genitourinary Syndrome of Menopause
• Intervention / Treatment: Drug: Cellular Matrix / A-CP-HA Kit; Drug: Local estrogen therapy (Blissel, estriol 50 micrograms/g vaginal gel)

Detailed Description

This study is a randomized, controlled, non-inferiority trial, with a second blind observer, comparing effectiveness of the use of Cellular Matrix / A-CP-HA Kit (a combination of autologous platelet-rich plasma and non-cross-linked hyaluronic acid) to the standard line of treatment, local estrogen therapy (Blissel, estriol 50 micrograms/g vaginal gel) in women with genitourinary syndrome of menopause (SGM). Duration of the study estimated is 24 months.

A total of 192 menopausal women, with absence of menstruation for at least 12 months, ≤70 years old, that are sexually active and who report symptoms and signs of SGM, with a vaginal health index <15 points. Patients will be excluded if are in treatment with systemic or local hormonal treatment in the last 3 months, Tamoxifen or Aromatase inhibitor treatments. Vulvovaginal pathologies (condyloma, vaginal intraepithelial neoplasia, vaginal carcinoma, lichen sclerosus, lichen planus, history of radiation, history of cervical cancer, other gynecologic cancer, or pelvic radiation, or active genital infection (eg. g., bacterial vaginosis, genital herpes, candida). Contraindication for vaginal estrogen therapy. Women with thrombocytopenia or coagulation disorders, systemic infections, STDs, cancer of any type in recent treatment, connective tissue diseases. Women who have had pelvic surgery within 6 months.

Patients will be randomized 1:1, equal number assigned to each of the two treatment groups, to receive treatment with two dose of Cellular Matrix / A-CP-HA Kit (a combination of autologous platelet-rich plasma and non-cross-linked hyaluronic acid), separated for a month, and control group that will receive the standard treatment for SGM, local estrogen therapy (Blissel, estriol 50 micrograms/g vaginal gel).

Patients will interviewed about their medical history, age of menopause, symptoms related and history of treatments. Evaluation of the Vaginal Health Index (VHIS), Vulvar Health Index (VHI), vaginal pH, and vaginal maturation index (vaginal cytology). The intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia and dysuria) will be measured using a 5-cm visual analog scale (VAS), and a valuation of Female Sexual Distress (FSD) score. Photographic monitoring during all phases of the procedure. Routine laboratory test serology will requested for both groups (valid up to 3 months).

Both groups will be follow-up for 3 and 6 month afther treatment, a blind observer will assess the application of the validated scale (VHIS, VHI), and the investigators will do the FSD, symptom record, maturation index, follow-up photography and evaluation of adverse events and treatment compliance and adherence.

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ignacio Rodríguez, MSc; Phone Number: 22029 0034932274700; Email: nacrod@dexeus.com
• Study Contact Backup: Name: Antonella de Ponte Davi, MD; Phone Number: 0034932274700; Email: ANTPON@dexeus.com

Study Locations

• Spain
  • Barcelona, Spain, 08037
    • Recruiting
    • Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus
    • Contact: Ignacio Rodríguez, BsC; Phone Number: 22029 0034932274700; Email: nacrod@dexeus.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women ≤70 years old
• Women that are sexually active
• Women who report symptoms and signs of SGM, with a vaginal health index (VHIS - Bachmann score) < 15 points.
• Women who understand the Spanish language
• Willing to participate in the study and sign informed consent.

Exclusion Criteria:

• Systemic or local hormonal treatment in the last 3 months
• Tamoxifen or Aromatase inhibitor treatments
• Vulvovaginal pathologies (condyloma, vaginal intraepithelial neoplasia, vaginal carcinoma, lichen sclerosus, lichen planus, history of radiation, history of cervical cancer, other gynecologic cancer, or pelvic radiation, or active genital infection (eg. g., bacterial vaginosis, genital herpes, candida) Contraindication for vaginal estrogen therapy
• Women with thrombocytopenia or coagulation disorders, systemic infections, STDs, cancer of any type in recent treatment, connective tissue diseases.
• Women who have had pelvic surgery within 6 months.
• Women who are unwilling or unable to give informed consent and/or do not comply with the study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cellular Matrix / A-CP-HA Kit; (a combination of autologous platelet-rich plasma and non-cross-linked hyaluronic acid) is a sterile tube designed for use in the preparation of a mixture of PRP and hyaluronic acid, tube is under vacuum allowing the withdrawal of 6 ml of blood and contains: 2 ml of hyaluronic acid gel (20mg/ml, 40 mg per tube) in phosphate buffer. Not crosslinked, hyaluronic acid is obtained from bacterial fermentation, 3 g of inert cell-selector gel, and 0.6 ml of anticoagulant (sodium citrate 4%). Centrifuged at 1,500 g, 3,000 rpm for 5 min. Platelet recovery of more than 70%, granulocyte depletion of 94.3% and red blood cells of 99.5% are achieved.	Drug: Cellular Matrix / A-CP-HA Kit; For infiltration, a prior preparation of the region with anesthetic cream is performed, procaine 25 mg/g + lidocaine 25 mg/g (Emla 5% cream) in the vulvar area and vaginal introitus. Occlusion of the area with plastic film is performed for 20 minutes. After asepsis and antisepsis, infiltration is performed with mesotherapy needles 31G 4mm, using the technique of superficial "point-to-point" mesotherapy microinjections, in the vestibule and the first 3 cm of the posterior wall of the vagina.
Active Comparator: Local estrogen therapy; Blissel, estriol 50 micrograms/g vaginal gel	Drug: Local estrogen therapy (Blissel, estriol 50 micrograms/g vaginal gel); Blissel®, Estriol vaginal gel 50 micrograms/g, daily application for 15-21 days in a row, then two times a week for 24 weeks (6 months). Application instructions will be explained to the patients. The gel should be applied in the vagina using an applicator with the marked dose, the full applicator should be inserted into the vagina and emptied, preferably at night.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with improved symptomatology.	Improvement is defined as having a higher score than the baseline in the Vaginal Health Index (VHIS)	at 6 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healing percentage	defined as percentage of patients scoring ≥ 15 in the VHIS	at 6 months after treatment
Evolution of Vaginal Health Index		at 3-months and 6-months follow-up
Evolution of Vulvar Health Index		at 3-months and 6-months follow-up
Evolution of vaginal pH		at 3-months and 6-months follow-up
Evolution of Vaginal maturation index (vaginal cytology)		at 3-months and 6-months follow-up
Evolution of intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia, and dysuria)	measured using a 5-cm visual analog scale (VAS)	at 3-months and 6-months follow-up
Incidence of adverse events and serious adverse events		at 3-months and 6-months follow-up

Collaborators and Investigators

• Sponsor: Fundación Santiago Dexeus Font
• Collaborators: Regen Lab SA

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 17, 2024
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens
• Other Study ID Numbers: FSD-CEL-2023-11; 2023-507200-31-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No