TREATMENT OF VAGINAL DRYNESS IN SJÖGREN'S DISEASE WITH CO2-LASER VERSUS TOPICAL PROMESTRIENE

Official title

TREATMENT OF VAGINAL DRYNESS IN SJÖGREN'S DISEASE WITH CO2-LASER VERSUS TOPICAL PROMESTRIENE: A PROSPECTIVE RANDOMIZED STUDY

Overview

Sjögren's disease (SjD) is a chronic, immune-mediated, systemic inflammatory disease characterized mainly by involvement of the salivary and lacrimal glands, causing symptoms of sicca syndrome. The disease predominantly affects women (9:1 to 20:1), with a peak incidence between 40 and 60 years of age. Symptoms of dryness include those resulting from vaginitis sicca, such as vulvovaginal irritation, dryness, pruritus, dyspareunia, polyuria, nocturia, dysuria, and urinary urgency/incontinence, which may begin before and worsen after menopause. These symptoms impact the sexual life and health-related quality of life of SjD patients. However, there are no specific recommendations for the management of vaginal dryness in this disease. Urogenital syndrome (UGS), a condition that affects women from the general population in the menopausal phase, is characterized by similar symptoms and can be treated with systemic or local hormone therapy (e.g., topical promestriene). Current data also demonstrate the efficacy and safety of vaginal fractional CO2 laser treatment for UGS. However, there are no studies on the efficacy of vaginal fractional CO2 laser and topical promestriene in the treatment of vaginal dryness in SjD.

Detailed description

This is a prospective randomized study lasting 6 months. Sixty SjD patients (pre- or post-menopausal) and with complaints of vaginal dryness will be included and randomized into two groups: 30 patients for the intervention group - vaginal fractional CO2 laser - and 30 patients for the comparator group - topical promestriene. Vaginal fractional CO2 laser applications will be performed once a month for three consecutive months. Patients in the group treated with promestriene will apply a 10 mg vaginal capsule at night for fifteen consecutive days and, after this period, one application every three days, until completing six months of treatment.

Interventions

• Device Fractional CO2 laser (vaginal)
  Vaginal fractional CO2 laser applications will be performed once a month for three consecutive months.
• Drug Promestriene Vaginal
  Patients in the group treated with promestriene will apply a 10 mg vaginal capsule at night for fifteen consecutive days and, after this period, one application every three days, until completing six months of treatment.

Primary outcome measures

• Vaginal Health Index (VHI) [Time frame: Four and six months]

Secondary outcome measures (7)

• 6-Item version of the Female Sexual Function Index (FSFI) [Time frame: Four and six months]
• Primary Sjögren's Syndrome Quality of Life questionnaire (PSSQoL) [Time frame: Four and six months]
• International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) [Time frame: Four and six months]
• Visual analogue scale (VAS) of vaginal dryness symptoms [Time frame: Four and six months]
• Persistence of the beneficial effects of laser therapy - visual analogue scale (VAS) of vaginal dryness symptoms [Time frame: Six months]
• Incidence of treatment-emergent adverse events (safety and tolerability) [Time frame: One month, two months, three months, four months, five months, six months]
• EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (safety and tolerability) [Time frame: Four and six months]

Eligibility criteria

Inclusion criteria

• Diagnosis of SjD according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria (2016).
• Controlled systemic disease activity \[EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)\] < 5 and without use of glucocorticoids or with a maximum dose of prednisone of 15 mg/day.
• Present complaints of vaginal dryness upon study entry.
• Agreeing to participate in the protocol according to the informed consent form signed before study inclusion.

Exclusion criteria

• History of breast, uterine or ovarian neoplasia, history of thromboembolic events, heart, kidney or liver failure.
• Other associated autoimmune rheumatic diseases, such as spondyloarthritis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis and mixed connective tissue disease.
• Conditions that may mimic SjD, such as history of head and neck radiation therapy, acquired immunodeficiency syndrome, hepatitis B and C, sarcoidosis, IgG4-related disease, and graft-versus-host disease.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 1 center

• University of Sao Paulo General Hospital — São Paulo

Publications

• Abstracts of the International Continence Society 31st annual meeting. Seoul, Korea, 18-21 September 2001. Neurourol Urodyn. 2001;20(4):371-576. No abstract available. PMID 11522151
• Tamanini JT, Dambros M, D'Ancona CA, Palma PC, Rodrigues Netto N Jr. [Validation of the "International Consultation on Incontinence Questionnaire -- Short Form" (ICIQ-SF) for Portuguese]. Rev Saude Publica. 2004 Jun;38(3):438-44. doi: 10.1590/s0034-89102004000300015. Epub 2004 Jul 8. Portuguese. PMID 15243675
• Dall'Agno ML, Ferreira CF, Ferreira FV, Perez-Lopez FR, Wender MCO. Validation of the Six-item Female Sexual Function Index in Middle-Aged Brazilian Women. Rev Bras Ginecol Obstet. 2019 Jul;41(7):432-439. doi: 10.1055/s-0039-1692694. Epub 2019 Jul 25. PMID 31344717
• Isidori AM, Pozza C, Esposito K, Giugliano D, Morano S, Vignozzi L, Corona G, Lenzi A, Jannini EA. Development and validation of a 6-item version of the female sexual function index (FSFI) as a diagnostic tool for female sexual dysfunction. J Sex Med. 2010 Mar;7(3):1139-46. doi: 10.1111/j.1743-6109.2009.01635.x. Epub 2009 Dec 1. PMID 19968774
• van Nimwegen JF, van der Tuuk K, Liefers SC, Verstappen GM, Visser A, Wijnsma RF, Vissink A, Hollema H, Mourits MJE, Bootsma H, Kroese FGM. Vaginal dryness in primary Sjogren's syndrome: a histopathological case-control study. Rheumatology (Oxford). 2020 Oct 1;59(10):2806-2815. doi: 10.1093/rheumatology/keaa017. PMID 32044981
• van Nimwegen JF, Arends S, van Zuiden GS, Vissink A, Kroese FG, Bootsma H. The impact of primary Sjogren's syndrome on female sexual function. Rheumatology (Oxford). 2015 Jul;54(7):1286-93. doi: 10.1093/rheumatology/keu522. Epub 2015 Feb 4. PMID 25652072
• Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X; International Sjogren's Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjogren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Coho PMID 27785888
• Serrano EV, Valim V, Miyamoto ST, Giovelli RA, Paganotti MA, Cade NV. Transcultural adaptation of the "EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI)" into Brazilian Portuguese. Rev Bras Reumatol. 2013 Nov-Dec;53(6):483-93. doi: 10.1016/j.rbr.2013.04.003. English, Portuguese. PMID 24477727

Identifiers

NCT: NCT07153276 · 67377523.3.0000.0068

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗