Vaginal Biorevitalization With Polydeoxyribonucleotides for the Improvement of the Genitourinary Syndrome of Menopause

NCT05464654 | Completed DMC

• 1 other identifier: 012-20170421
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study was to compare the efficacy of vaginal biorevitalization to improve the genitourinary syndrome of menopause (GSM) between the gold-standard treatment with local estrogen-based hormone therapy versus local salmon polydeoxyribonucleotide (PDRN) therapy.

Conditions

Genitourinary Syndrome of Menopause; Postmenopausal Disorder; Menopause; Vagina Atrophy

Keywords

Polynucleotides; Genitourinary syndrome of menopause; Postmenopause; Vagina atrophy; Vaginal biorevitalization

Outcome Measures

Primary Outcomes (9)

• Change from baseline urogenital domain score in the Menopause Rating Scale (MRS) at 3 months

  Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Items 9, 10 and 11 evaluate the urogenital domain. 0 points were considered asymptomatic, 1point indicated mild symptoms, 2-3 points moderate symptoms and \> 4 indicated severe symptoms.

  3 months

• Change from baseline Item 9 Menopause Rating Scale (MRS) total score at 3 months

  Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Item 9 assesses the severity of sexual problems, including changes in libido, sexual activity, and dyspareunia. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms.

  3 months

• Change from baseline Item 10 Menopause Rating Scale (MRS) total score at 3 months

  Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Item 10 assesses the severity of urinary problems such as polyuria, urinary urgency, bladder instability, and urinary incontinence. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms.

  3 months

• Change from baseline Item 11 Menopause Rating Scale (MRS) total score at 3 months

  Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Item 11 assesses the severity of vaginal dryness. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms.

  3 months

• Change from baseline Vaginal Maturity Index (VMI) at 3 months

  The vaginal maturation index (VMI) is used to assess the hormonal status of the vaginal epithelium, which quantifies the proportions of cell types in the vaginal epithelium. The VMI was evaluated through vaginal cytology, where the percentage of basal/parabasal, intermediate and superficial cells were calculated.

  3 months

• Change from baseline Estrogenic Effect at 3 months

  The estrogenic effect is used to evaluate the local action of estrogens in the vaginal epithelium. The higher value, it means that it is having a greater trophic effect due to local estrogen stimulation. To calculate this outcome, it was used the next formula: Estrogenic effect= \[(% of basal/parabasal cells\*0)+(% of intermediate cells\*0.5)+(% of superficial cells\*1)\]

  3 months

• Change from baseline Oxford grading scale at 3 months

  The Oxford grading scale evaluates the contraction capacity of the muscles of the pelvic floor. It was used at the time of vaginal examination. 0 points meant no contraction , 1 point a flicker contraction, 2 points a weak contraction, 3 points a moderate contraction, 4 points a good contraction, and 5 points a strong contraction.

  3 months

• Change from baseline vaginal pH at 3 months

  Vaginal pH tests measure the acidity of the vagina. A normal vaginal pH value was considered when it was between 4.0 and 5.

  3 months

• Change from baseline colposcopic findings at 3 months

  The presence or absence of vaginal folds, paleness and vaginal lesions were colposcopic findings that were evaluated as nominal dichotomous variables. Lugol's staining was performed during colposcopy. The degree of Lugol's staining was evaluated as an ordinal variable with 4 degrees, depending on the intensity of staining of the vaginal mucosa.

  3 months

Study Arms (2)

Polynucleotide vaginal suppositories

EXPERIMENTAL

In this arm 72 first-time participants of the "peri-postmenopause and bone metabolism clinic" of the "Regional Hospital October 1st " of ISSSTE Mexico, were randomly enrolled to be treated with local salmon polydeoxyribonucleotide (PDRN) therapy.

Drug: 3 g Polynucleotide vaginal suppositories

Conjugated estrogens cream

ACTIVE COMPARATOR

In this arm 64 first-time participants of the "peri-postmenopause and bone metabolism clinic" of the "Regional Hospital October 1st " of ISSSTE Mexico, were randomly enrolled to be treated with the gold-standard treatment with local estrogen-based hormone therapy.

Drug: Conjugated estrogens cream 1g Tube

Interventions

3 g Polynucleotide vaginal suppositories DRUG

3 g polynucleotide vaginal suppositories were administered nightly for 6 days.

Also known as: Tunover®

Polynucleotide vaginal suppositories

Conjugated estrogens cream 1g Tube DRUG

Conjugated estrogen cream 1g was applied intravaginally on Monday, Wednesday and Friday for three months.

Also known as: Generic

Conjugated estrogens cream

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First-time patients with the diagnosis of Genitourinary Syndrome of Menopause with an MRS \> 5 in the urogenital domain, with alterations in the vaginal maturity index (VMI).

You may not qualify if:

• Incomplete clinical records.
• History of prolonged use of steroids.
• Use of alternative local therapies applied in the vagina's mucosa.
• Use of local therapies with vaginal suppositories for any reason 15 days before the beginning of the study.
• Clinical evidence of infectious cervical-vaginitis or vulvovaginitis.
• Evidence of urinary tract infection (UTI).
• Lack of adherence to medical treatment.
• Diagnosis of cancer.
• Diagnosis of depression.
• Diagnosis of uncontrolled primary or secondary immunodeficiencies.
• Allergies to any of the medications administered.
• BIRADS \>2 or high risk of developing breast cancer, ovarian cancer or endometrial cancer.
• Use of oral hormonal or non-hormanl therapy.

Sponsors & Collaborators

• Hospital Regional 1o de Octubre: lead
• Hospital General Regional No. 1 IMSS: collaborator
• Universidad Nacional Autonoma de Mexico: collaborator
• National Polytechnic Institute, Mexico: collaborator

Study Sites (1)

Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE

Mexico City, 07300, Mexico

Location

Related Publications (11)

• The NAMS 2020 GSM Position Statement Editorial Panel. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020 Sep;27(9):976-992. doi: 10.1097/GME.0000000000001609.

  PMID: 32852449 BACKGROUND

• Schneider HP, Heinemann LA, Rosemeier HP, Potthoff P, Behre HM. The Menopause Rating Scale (MRS): reliability of scores of menopausal complaints. Climacteric. 2000 Mar;3(1):59-64. doi: 10.3109/13697130009167600.

  PMID: 11910611 BACKGROUND

• Heinemann K, Assmann A, Mohner S, Schneider HP, Heinemann LA. [Reliability of the Menopause Rating Scale (MRS): Investigation in the German population]. Zentralbl Gynakol. 2002 Mar;124(3):161-3. doi: 10.1055/s-2002-32268. German.

  PMID: 12070795 BACKGROUND

• Schneider HP, Rosemeier HP, Schnitker J, Gerbsch S, Turck R. Application and factor analysis of the menopause rating scale [MRS] in a post-marketing surveillance study of Climen. Maturitas. 2000 Dec 29;37(2):113-24. doi: 10.1016/s0378-5122(00)00177-8.

  PMID: 11137330 BACKGROUND

• Heinemann K, Ruebig A, Potthoff P, Schneider HP, Strelow F, Heinemann LA, Do MT. The Menopause Rating Scale (MRS) scale: a methodological review. Health Qual Life Outcomes. 2004 Sep 2;2:45. doi: 10.1186/1477-7525-2-45.

  PMID: 15345062 BACKGROUND

• Weber MA, Limpens J, Roovers JP. Assessment of vaginal atrophy: a review. Int Urogynecol J. 2015 Jan;26(1):15-28. doi: 10.1007/s00192-014-2464-0. Epub 2014 Jul 22.

  PMID: 25047897 BACKGROUND

• McCracken JM, Balaji S, Keswani SG, Hakim JC. An Avant-Garde Model of Injury-Induced Regenerative Vaginal Wound Healing. Adv Wound Care (New Rochelle). 2021 Apr;10(4):165-173. doi: 10.1089/wound.2020.1198. Epub 2020 Aug 10.

  PMID: 32602816 BACKGROUND

• Chung HS, Lee HS, Park K. Estrogen modulates epithelial progenitor cells in rat vagina. Investig Clin Urol. 2021 May;62(3):349-353. doi: 10.4111/icu.20200513. Epub 2021 Apr 2.

  PMID: 33834644 BACKGROUND

• Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526.

  PMID: 25415166 BACKGROUND

• Nappi RE, Martini E, Cucinella L, Martella S, Tiranini L, Inzoli A, Brambilla E, Bosoni D, Cassani C, Gardella B. Addressing Vulvovaginal Atrophy (VVA)/Genitourinary Syndrome of Menopause (GSM) for Healthy Aging in Women. Front Endocrinol (Lausanne). 2019 Aug 21;10:561. doi: 10.3389/fendo.2019.00561. eCollection 2019.

  PMID: 31496993 BACKGROUND

• The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017 Jul;24(7):728-753. doi: 10.1097/GME.0000000000000921.

  PMID: 28650869 RESULT

MeSH Terms

Interventions

Drugs, Generic

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Juan M Ocampo-Godinez, M.D., Ph.D.

  Laboratorio de Bioingenieria de Tejidos, UNAM

  STUDY DIRECTOR

• Patricia Loranca-Moreno, M.D., M.Sc.

  Hospital Regional 1o de Octubre, ISSSTE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The pathologist and colposcopists were blinded to the treatment the participants received.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomised clinical trial was conducted in 136 postmenopausal women with GSM from the "peri-postmenopause and bone metabolism clinic" of the "Regional Hospital October 1st " of ISSSTE, Mexico, from June to December 2021. The control group (n=64) received local estrogen-based hormonal therapy, applied to the vagina mucosa on Monday, Wednesday, and Friday of each week, for 3 months, while the experimental group (n=72) received local salmon PDRNs on vaginal suppositories, applied solely for six days every night in the first week. The follow-up assessment was done after 3 months.

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 19, 2022
• Study Start: June 23, 2021
• Primary Completion: November 23, 2021
• Study Completion: December 31, 2022
• Last Updated: April 11, 2023

Record last verified: 2023-04

Locations

ME (1)