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Vulvodynia (Vd) is chronic functional vulvar pain, with prevalence of 3-16% and unclear etiopathology. Although Vd significantly deteriorates quality of life, the problem is marginalized, no pharmacologic treatment standards exist. Naltrexone hydrochloride is a specific opioid antagonist with slight agonist activity. There is growing body of evidence supporting the effectiveness of low-dose naltrexone (LDN) in different types of chronic pain. The main goal of this trial is to test the effect of LDN on pain perception and quality of life in women with different types of Vd. Half of the study population receives LDN and the remaining patients take placebo, according to randomization list. This RTC is quadruplet blinded.
In this Randomized Controlled Trial the effectiveness of LDN in reducing chronic pain and improvement of quality of life in women with provoked, spontaneous or mixed vulvodynia is assessed on the basis of the test results recommended according to IMMPACT protocol, compared to the placebo arm. Patients remain in the study for 6 months (4 months of treatment with LDN or placebo). There are 5 visits by a gynecologist (diagnosis of vulvodynia, inclusion and exclusion criteria, randomization), nurse, psychologist and physiotherapist: screening, randomization, control telephone visit, final visit and telephone summary visit. Pain perception and quality of life estimation is reported by the patient in e-diary, validated psychology questionnaires are fulfilled and physical examination acc. Fascial Manipulation (CFMS) L. Stecco method is performed. Tolerability of LDN therapy will also be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Naltrexone | Experimental | NALTREXONE HYDROCHLORIDE 4,5 mg, coated oral tablets, 1xd. for 4 months |
|
| Placebo | Placebo Comparator | Placebo, coated oral tablets, 1xd. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Naltrexone Hydrochloride | Drug | treatment of vulvodynia |
|
| Measure | Description | Time Frame |
|---|---|---|
| Treatment effectiveness - change in pain intensity | measured by 11-point NRS scale based on spontaneously experienced vulvar and vaginal pain and during vaginal penetration | from pre-treatment values (VISIT 2) to end of treatment values (VISIT 4) assessed for 4 months |
| Treatment effectiveness - change in type and severity of pain | measured by McGill Questionnaire (SF-MPQ) | from pre-treatment values (VISIT 2) to end of treatment values (VISIT 4) assessed for 4 months |
| Treatment effectiveness - change in emotional functioning | Beck Depression Inventory (BDI-II) | from pre-treatment values (VISIT 2) to end of treatment values (VISIT 4) assessed for 4 months |
| Patient's satisfaction | measured by 11-point Lickert scale | from pre-treatment values (VISIT 2) to end of treatment values (VISIT 4) assessed for 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment tolerability | Assessment of the tolerability of LDN therapy based on the assessment of side effects and adverse events | throughout the treatment period (from VISIT 2 to VISIT 4) assessed for 4 months |
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Inclusion Criteria:
Exclusion Criteria:
Severe, hepatic and renal dysfunction defined as:
i. An ASPT or ALT result 5 times the upper limit; ii. The level of bilirubin 3 times above the upper limit of normal - excluding patients with Gilbert's syndrome; iii. EGFR result below 30 ml / min / m2, on the basis of historical studies not older than 3 years before the screening visit or from the tests performed during the screening visit according with point 12 of the Protocol, version 1.0 of March 28, 2022.
Abuse of alcohol (more than 14 units per week) and other stimulants. 3. Taking psychoactive substances, including drugs, except for SSRI, SNRI, SARI (Trazodone), and anticonvulsants (Gabapentin, Pregabalin, Lamotrigine) in fixed doses from the screening visit.
4. Taking opioid drugs in the last 2 months before the screening visit (also in OTC preparations, eg Loperamide).
5. Taking naltrexone hydrochloride and Mysimba for weight loss at any time in your life.
6. BTA injection in the vulva in the last 4 months before the screening visit. 7. Endovascular procedures in the area of the small pelvis in the last 6 months before the screening visit.
8. Previous surgical procedures requiring general anesthesia (with general anesthesia) in the last 2 months before the screening visit.
9. Completed multidisciplinary therapeutic program in the treatment of vulvodynia in the last 4 months before the screening visit.
10. Diseases of the vulva: lichen, current contact vulvovaginitis, bacterial and / or yeast infections, other dermatological diseases, recurrent genital herpes (HSV; min 4 times / year).
11. Diagnosis of current or past serious mental disorders according to the criteria of ICD-10 and DSM-5, including psychotic and organic disorders (except depression and anxiety disorders).
12. Gynecological abnormalities requiring medical treatment: current HSIL, CIN II / III, pelvic inflammation, mixed or solid ovarian tumors, simple ovarian cysts greater than 5 cm, abnormal vaginal inter-cycle bleeding.
13. Pelvic venous diseases (PeVD), 4 criteria met on USG. 14. Pregnancy and lactation. 15. Spastic diseases: multiple sclerosis (MS), connective tissue diseases (Marfan syndrome and marfan-like syndromes), reactive arthritis (RA). 16. Vaginismus, Lamont scale 3-5 (gynecological examination impossible due to anxiety).
17. Significant and / or uncorrected disability in the field of sight or hearing, making it difficult to perform psychological tests.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrzej Stepulak, Professor | Contact | 448 52 98 | 0048 81 | cwnr@umlub.pl |
| Name | Affiliation | Role |
|---|---|---|
| Ewa Baszak-Radomańska, MD, PhD | Terpa Limited Liability Company Limited partnership | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Terpa Limited Liability Company Limited Partnership | Recruiting | Lublin | 20-333 | Poland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33757151 | Background | Baszak-Radomanska E, Wanczyk-Baszak J, Paszkowski T. Pilot study of testing a clinical tool for pelvic physical examination in patients with vulvodynia. Ginekol Pol. 2021 Mar 23. doi: 10.5603/GP.a2020.0168. Online ahead of print. | |
| 40590401 | Derived | Baszak-Radomanska E, Wanczyk-Baszak J, Paszkowski T. Pelvic floor examination in vulvodynia: VAMP protocol validation in correlation with central sensitization. Womens Health (Lond). 2025 Jan-Dec;21:17455057251338410. doi: 10.1177/17455057251338410. Epub 2025 Jul 1. |
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| ID | Term |
|---|---|
| D056650 | Vulvodynia |
| ID | Term |
|---|---|
| D014845 | Vulvar Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D009271 | Naltrexone |
| ID | Term |
|---|---|
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 |
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| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |