Botulinum toxin injected into the uterine muscle to reduce severe menstrual pain
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
This trial will test whether a single botulinum toxin injection into the uterine wall via hysteroscopy can reduce severe menstrual cramps in women who did not get relief from first-line hormonal and pain treatments, compared with a placebo injection.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 222 (estimated) |
| Ages | 18 Years and up |
| Sex | Female |
| Sponsor | Nantes University Hospital Academic / other |
| Locations | 8 sites (Aix-en-Provence and 7 other locations) |
| Trial ID | NCT06995287 on ClinicalTrials.gov |
What this trial studies
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial comparing a single intramyometrial injection of botulinum toxin (Xeomin) delivered by hysteroscopy versus a placebo injection in women with severe primary dysmenorrhea. Participants must be premenopausal adult women with an average pain score of at least 6/10 who have failed optimized first-line therapy and have pelvic MRI excluding deep infiltrating endometriosis. Randomization is stratified by center and participants are followed for six months, with the primary outcome being global impression of improvement at three months. The design includes blinded outcome assessment to compare analgesic effect and safety between active treatment and placebo.
Who should consider this trial
Good fit: Premenopausal adult women with severe primary dysmenorrhea (average NRS ≥6) who have failed combined hormonal therapy and appropriate analgesics, have pelvic MRI excluding deep endometriosis or endometrioma, and use a highly effective method of contraception are ideal candidates.
Not a fit: Women with MRI evidence of deep infiltrating endometriosis or endometrioma, menopausal women, or those with contraindications to botulinum toxin are unlikely to benefit from this intervention.
Why it matters
Potential benefit: If effective, this approach could offer a new, minimally invasive option to reduce severe menstrual pain for women who have not improved with standard medical therapy.
How similar studies have performed: Small pilot studies and case series of local uterine or myometrial botulinum toxin injections have reported symptomatic improvement, but robust randomized Phase 3 data are limited.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Aix-en-Provence and 7 other locations
- 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)
- 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)
Study contacts
- Study coordinator: Claire CARDAILLAC
- Email: claire.cardaillac@chu-nantes.fr
- Phone: +33 2 53 48 23 50
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.