Clinical trial NCT06995287: Evaluation of the Analgesic Effect of Intramyometrial Botulinum Toxin Injection Via Hysteroscopy in Severe Primary Dysmenorrhea
Official title: Evaluation of the Analgesic Effect of Intramyometrial Botulinum Toxin Injection Via Hysteroscopy in Severe Primary Dysmenorrhea: a Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Primary Dysmenorrhea
Chronic Pelvic Pain
Keywords: Primary dysmenorrhea
injection
Botulimum toxin, Type A
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Merz Pharmaceuticals GmbH
name: Ministry of Health, France
First posted: 2025-05-29
Enrollment: 222
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Patient Global Improvement
timeFrame: 3 months
Secondary outcomes:
measure: Average intensity of dysmenorrhea
timeFrame: 6 months
measure: Maximum intensity of dysmenorrhea
timeFrame: 6 months
measure: Duration of dysmenorrhea
timeFrame: 6 months
measure: Average intensity of non-menstrual pelvic pain
timeFrame: 6 months
measure: Maximum intensity of non-menstrual pelvic pain
timeFrame: 6 months
measure: Duration of non-menstrual pelvic pain
timeFrame: 6 months
measure: Average intensity of pain during the most recent sexual intercourse
timeFrame: 6 months
measure: Sexual function assessed using the Female Sexual Function Index
timeFrame: 6 months
measure: Central sensitization to pain
timeFrame: 3 months
measure: Heavy menstrual bleeding assessed using the Higham score
timeFrame: 6 months
measure: General quality of life
timeFrame: 6 months
measure: Disease-specific quality of life
timeFrame: 6 months
measure: Number of days of school or work absenteeism
timeFrame: 6 months
measure: Anxiety assessed using the State and Tait Anxiety Inventoy-Y scale
timeFrame: 3 months
measure: Depression evaluated using the Beck Depression Inventory-II
timeFrame: 3 months
measure: Global improvement percentage
timeFrame: 6 months
measure: Pain intensity during the procedure
timeFrame: during procedure
measure: Pain intensity at 5 minutes post-procedure
timeFrame: 5 minutes post-procedure
measure: Adverse events related to the injections
timeFrame: 6 months
measure: Emergency visits following the procedure
timeFrame: 1 month
measure: Exploratory analysis for the MEOPA subgroup : Primary Outcome
timeFrame: 3 months
measure: Exploratory analysis for the MEOPA subgroup : Pain intensity during the procedure
timeFrame: during procedure
measure: Exploratory analysis for the MEOPA subgroup: Willingness to repeat the intervention
timeFrame: 6 months
measure: Exploratory analysis for the MEOPA subgroup: Adverse event
timeFrame: 6 months
measure: Exploratory analysis for the MEOPA subgroup : Emergency visits
timeFrame: 6 months
measure: Exploratory analysis for the hormonal treatment subgroup : Primary Outcome
timeFrame: 3 months
measure: Exploratory analysis for the hormonal treatment subgroup : Pain intensity during the procedure
timeFrame: during procedure
measure: Exploratory analysis for the hormonal treatment subgroup : Willingness to repeat the intervention
timeFrame: 6 months
measure: Exploratory analysis for the hormonal treatment subgroup : Adverse event
timeFrame: 6 months
measure: Exploratory analysis for the hormonal treatment subgroup : Emergency visits
timeFrame: 6 months
Other outcomes:
Locations:
city: Aix en Provence
country: France
facility: Clinique axium / Centre resilience
city: Angers
country: France
facility: CHU Angers
city: Brest
country: France
facility: CHU Brest
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Nantes
country: France
facility: CHU Nantes
city: Nantes
country: France
facility: Clinique Brétéché
city: Rennes
country: France
facility: CHU Rennes
Study officials:
References: