Evaluation of the Analgesic Effect of Intramyometrial Botulinum Toxin Injection Via Hysteroscopy in Severe Primary Dysmenorrhea

Phase 3RecruitingNCT06995287

Nantes University Hospital222 enrolled

Overview

The objective of the study is to evaluate the global impression of improvement at 3 months following intramyometrial botulinum toxin injections via hysteroscopy in women with severe primary dysmenorrhea who have failed first-line medical treatment, compared to intramyometrial placebo injections.

This trial is multicenter, placebo-controlled, randomized with center-based stratification, double-blind and prospective. The treatment consists of a single injection follow by 6 months of follow-up.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

222

Conditions

Primary Dysmenorrhea Chronic Pelvic Pain

Interventions

XeominDRUG

One injection will be performed via hysteroscopy under local anesthesia.

PlaceboDRUG

One injection will be performed via hysteroscopy under local anesthesia.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult women who are not menopausal, * Experiencing severe dysmenorrhea, defined as an average pain intensity score ≥ 6/10 on a Numerical Rating Scale (NRS) over the past 3 months at the inclusion visit, * Having failed optimal first-line medical treatment combining hormonal therapy and appropriate analgesics (Level I and II analgesics, and NSAIDs), * Having undergone a pelvic MRI within 6 months prior to the inclusion visit that shows no evidence of deep infiltrating endometriosis or endometrioma, following systematic review by radiologists from the expert center managing the patient (if the pelvic MRI is deemed of insufficient quality for interpretation, a new MRI will be performed at the center), * Using a highly effective method of contraception (failure rate \<1%) for the entire duration of the follow-up period. Highly effective contraception methods are defined as one of the following: combined hormonal contraception (containing estrogen and progestin) with ovulation inhibition (oral, vaginal, or transdermal), progestin-only hormonal contraception with ovulation inhibition (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormonal system (IUS), condoms, bilateral tubal occlusion, vasectomized partner, or sexual abstinence, * Having a negative urine pregnancy test on the day of the procedure, * Having signed the informed consent form for the study at the M-1 visit. Exclusion Criteria: * Pregnant or planning a pregnancy during the entire study period, * Currently breastfeeding, * Refusal to use effective contraception during the study and for 6 months after its completion, * Contraindications to botulinum toxin, including: * Generalized disorders of muscular activity (e.g., myasthenia gravis, Lambert-Eaton syndrome), * Ongoing treatment with aminoglycosides, peripheral muscle relaxants, or amino-4-quinolines, * Hypersensitivity to the active substance, human albumin, or sucrose, * Bleeding disorders or current treatment with anticoagulants, * Ongoing vaginal or upper genital tract infection, * Participation in another interventional clinical trial, * Inability to cooperate or understand the study requirements in a way that would allow strict adherence to the protocol, * Subject to legal protection measures (e.g., guardianship, curatorship, or judicial protection), * Not affiliated with the French social security system, * Unable to access the internet to complete questionnaires at Month 1 and Month 6.

Locations (8)

Clinique axium / Centre resilience

Aix-en-Provence, France

NOT_YET_RECRUITING

CHU Angers

Angers, France

NOT_YET_RECRUITING

CHU Brest

Brest, France

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

Patient Global Improvement

The response (favorable versus unfavorable) to the Patient Global Impression of Improvement questionnaire at 3 months following intra-myometrial injection. A response is considered favorable when the score of Patient Global Impression of Improvement questionnaire is 1 or 2. Patient Global Impression of Improvement questionnaire is self-assessment scale ranging from 1 (Very much improved) to 7 (Very much worsened).

Time frame: 3 months

Secondary Outcomes

Average intensity of dysmenorrhea

Average intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: 6 months

Maximum intensity of dysmenorrhea

Maximum intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: 6 months

Duration of dysmenorrhea

Duration (in days) of dysmenorrhea during the last menstrual cycle before injection, then at 3 and 6 months.

Time frame: 6 months

Average intensity of non-menstrual pelvic pain

Average intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: 6 months

Maximum intensity of non-menstrual pelvic pain

Central Contacts

Claire CARDAILLAC

CONTACT

+33 2 53 48 23 50 claire.cardaillac@chu-nantes.fr

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

CHU Lille

Lille, France

NOT_YET_RECRUITING

Hôpital de la Croix-Rousse

Lyon, France

NOT_YET_RECRUITING

CHU Nantes

Nantes, France

RECRUITING

Clinique Brétéché

Nantes, France

NOT_YET_RECRUITING

CHU Rennes

Rennes, France

NOT_YET_RECRUITING

Maximum intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: 6 months

Duration of non-menstrual pelvic pain

Duration of non-menstrual pelvic pain (in days) evaluated before injection, then at 1, 3, and 6 months

Time frame: 6 months

Average intensity of pain during the most recent sexual intercourse

Average intensity of pain during the most recent sexual intercourse, evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: 6 months

Sexual function assessed using the Female Sexual Function Index

Sexual function assessed using the Female Sexual Function Index before injection, and then at 1, 3, and 6 months. The Female Sexual Function Index consists of 19 items assessing six dimensions of female sexual function (desire, arousal, pain, lubrication, satisfaction, orgasm). The total score ranges from 2 to 36, with sexual dysfunction defined as a score below 23.

Time frame: 6 months

Central sensitization to pain

Central sensitization to pain assessed using the Convergences PP score, before injection and at 3 months. The total Convergence PP score ranges from 0 to 10, with pelvic hypersensitivity defined as a score greater than or equal to 5.

Time frame: 3 months

Heavy menstrual bleeding assessed using the Higham score

Heavy menstrual bleeding assessed using the Higham score during the last menstrual period, before injection, and at 3 and 6 months. The Higham score is an objective assessment score of menstrual blood loss. Each day of menstruation, the patiente counts the number of pads or tampons used, referring to a visual chart. A score above 100 points corresponds to a blood loss of 80 mL, which defines menorrhagia.

Time frame: 6 months

General quality of life

General quality of life assessed using the The Short Form (36) Health Survey before injection, and at 1, 3, and 6 months. The questionnaire The Short Form (36) Health Survey is a multidimensional, generic scale, meaning it assesses health status regardless of the underlying condition, gender, age, or treatment. Its 36 items evaluate 8 domains: physical activity, physical role limitations, bodily pain, perceived health, vitality, social functioning, emotional state, and mental health. Each item is scored from 0 (lowest score) to 100 (highest score). At the end, a score for each SF-36 dimension is calculated based on the corresponding items, ranging from 0 (poor quality of life) to 100 (best quality of life).

Time frame: 6 months

Disease-specific quality of life

Disease-specific quality of life assessed using the Endometriosis Health Profile EHP-5 questionnaire (it is the short version of Endometriosis Health Profile EHP-30) before injection, and at 1, 3, and 6 months. This short questionnaire includes only 11 out of 30 questions, to which patients must respond with Always, Often, Sometimes, Rarely, or Never. This questionnaire ranging from 0 (the best health status) to 44 (the worst health status).

Time frame: 6 months

Number of days of school or work absenteeism

Number of days of school or work absenteeism in the past month, assessed before injection and at 1, 3, and 6 months.

Time frame: 6 months

Anxiety assessed using the State and Tait Anxiety Inventoy-Y scale

Anxiety assessed using the State and Tait Anxiety Inventoy scale-Y before injection and at 3 months. This State and Tait Anxiety Inventoy scale-Y includes two distinct scales for assessing state anxiety (STAI Form Y-A) and trait anxiety (STAI Form Y-B). The Trait Anxiety scale consists of 20 items and assesses the individual's general tendency to experience anxiety. Scores range from 21 to 77. The State Anxiety scale also includes 20 items and measures a temporary anxious mood (stress). Scores range from 20 to 80.

Time frame: 3 months

Depression evaluated using the Beck Depression Inventory-II

Depression evaluated using the Beck Depression Inventory-II before injection and at 3 months. This is a self-administered questionnaire consisting of 21 items. Each item includes 4 statements corresponding to increasing levels of symptom intensity, rated on a scale from 0 to 3. The total score is obtained by summing the scores of the 21 items. The score can be interpreted according to the following four categories: no depression (score \< 10); mild depression (10 \< score \< 18); moderate depression (19 \< score \< 29); and severe depression (score \> 30).

Time frame: 3 months

Global improvement percentage

Global improvement percentage (0-100%) assessed at 1, 3, and 6 months.

Time frame: 6 months

Pain intensity during the procedure

Pain intensity during the procedure assessed via numerical rating scale. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: during procedure

Pain intensity at 5 minutes post-procedure

Pain intensity at 5 minutes post-procedure, assessed via numerical rating scale

Time frame: 5 minutes post-procedure

Adverse events related to the injections

Adverse events related to the injections, recorded immediately postoperatively, and at 1, 3, and 6 months.

Time frame: 6 months

Emergency visits following the procedure

Emergency visits following the procedure, assessed at 1 month.

Time frame: 1 month

Exploratory analysis for the MEOPA subgroup : Primary Outcome

Exploratory analysis for the MEOPA subgroup: Primary outcome. The response (favorable versus unfavorable) to the Patient Global Impression of Improvement questionnaire at 3 months following intra-myometrial injection. A response is considered favorable when the score of Patient Global Impression of Improvement questionnaire is 1 or 2. Patient Global Impression of Improvement questionnaire is self-assessment scale ranging from 1 (Very much improved) to 7 (Very much worsened).

Time frame: 3 months

Exploratory analysis for the MEOPA subgroup : Pain intensity during the procedure

Exploratory analysis for the MEOPA subgroup : procedural pain. Pain intensity during the procedure assessed via numerical rating scale. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: during procedure

Exploratory analysis for the MEOPA subgroup: Willingness to repeat the intervention

Exploratory analysis for the MEOPA subgroup: willingness to repeat the intervention. The response is rating Yes or No.

Time frame: 6 months

Exploratory analysis for the MEOPA subgroup: Adverse event

Exploratory analysis for the MEOPA subgroup: adverse events.

Time frame: 6 months

Exploratory analysis for the MEOPA subgroup : Emergency visits

Exploratory analysis for the MEOPA subgroup : emergency visits.

Time frame: 6 months

Exploratory analysis for the hormonal treatment subgroup : Primary Outcome

Exploratory analysis for the hormonal treatment subgroup : Primary outcome. The response (favorable versus unfavorable) to the Patient Global Impression of Improvement questionnaire at 3 months following intra-myometrial injection. A response is considered favorable when the score of Patient Global Impression of Improvement questionnaire is 1 or 2. Patient Global Impression of Improvement questionnaire is self-assessment scale ranging from 1 (Very much improved) to 7 (Very much worsened).

Time frame: 3 months

Exploratory analysis for the hormonal treatment subgroup : Pain intensity during the procedure

Exploratory analysis for the hormonal treatment subgroup : procedural pain. Pain intensity during the procedure assessed via numerical rating scale. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Time frame: during procedure

Exploratory analysis for the hormonal treatment subgroup : Willingness to repeat the intervention

Exploratory analysis for the hormonal treatment subgroup : willingness to repeat the intervention. The response is rating Yes or No.

Time frame: 6 months

Exploratory analysis for the hormonal treatment subgroup : Adverse event

Exploratory analysis for the hormonal treatment subgroup : adverse events.

Time frame: 6 months

Exploratory analysis for the hormonal treatment subgroup : Emergency visits

Exploratory analysis for the hormonal treatment subgroup : emergency visits.

Time frame: 6 months