Evaluation of the Analgesic Effect of Intramyometrial Botulinum Toxin Injection via Hysteroscopy in Severe Primary Dysmenorrhea: A Prospective, Multicenter, Double-Blind, Randomized Placebo-Controlled Study. HYSTEROXINE Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

9 Feb 2026 → ongoing

Decision date (initial)

2025-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS (PHRC-Interrégional 2023)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Evaluation of the global impression of improvement at 3 months following treatment with intra-myometrial botulinum toxin injections via hysteroscopy in women with severe primary dysmenorrhea unresponsive to first-line medical treatment, compared to intra-myometrial placebo injections.

Secondary objectives 15

1. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on the intensity and duration of dysmenorrhea
2. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on the intensity and duration of pelvic pain outside of menstruation
3. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on the intensity of pain during intercourse (dyspareunia)
4. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on the overall sexual quality of life of patients
5. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on pain hypersensitivity
6. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on the volume and duration of bleeding during menstruation
7. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on the overall and disease-specific quality of life of patients
8. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on school or work absenteeism
9. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on pain-related anxiety and depression
10. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on patient satisfaction with the treatment received
11. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on injection tolerance
12. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on injection-related adverse effects
13. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy on the number of postoperative emergency consultations
14. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy in the subgroup "patients who have received MEOPA"
15. Evaluation of the effect of intra-myometrial botulinum toxin injections via hysteroscopy in the subgroup "patients who have received hormonal treatment"

Conditions and MedDRA coding

Severe primary dysmenorrhea

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adult women who are not menopausal
2. Experiencing severe dysmenorrhea, defined by an average pain intensity score of ≥ 6/10 on a Visual Analog Scale over the past 3 months at the inclusion visit
3. Having failed optimal first-line medical treatment combining hormonal therapy and appropriate analgesics (Step I and II, NSAIDs)
4. Having a pelvic MRI performed within 6 months prior to the inclusion visit, showing no evidence of deep pelvic endometriosis, endometriomas or myoma after systematic re-evaluation by the radiologists at the expert center managing the patient (if the pelvic MRI is deemed of insufficient quality for interpretation, it will be repeated at the center).
5. Using a highly effective contraception method (failure rate <1%) for the entire duration of the patient's follow-up. Highly effective contraception methods are defined as one of the following: combined hormonal contraception (containing estrogens and progestins) with ovulation inhibition (oral, intravaginal, transdermal), progestin-only hormonal contraception with ovulation inhibition (oral, injectable, implantable), intrauterine device (IUD), hormone-releasing intrauterine system (IUS), condoms, bilateral tubal occlusion, vasectomized partner, sexual abstinence.
6. Presenting with a negative blood pregnancy test at the inclusion visit and a negative urine test on the day of the procedure.
7. Having signed the informed consent for the study no later than Day 0

Exclusion criteria 16

1. Pregnant patient or planning pregnancy throughout the duration of the study
2. Not being affiliated with the French Social Security system
3. Not having the ability to connect to the internet to complete the questionnaires at M1 and M6
4. Unexpected discovery of an endocavitary lesion not previously diagnosed (polyp, fibroid, or uterine malformation) during the Day 0 visit.
5. Currently breastfeeding
6. Refusal to use highly effective contraception during the study and for the 6 months following the study
7. Having a contraindication to botulinum toxin: - Generalized muscle activity disorders (myasthenia, Lambert-Eaton syndrome), - Ongoing treatment with aminoglycosides, peripheral muscle relaxants, or amino-4-quinolines, - Hypersensitivity to the active substance, human albumin, or sucrose
8. Having coagulation disorders
9. Having an active vaginal or upper genital infection
10. Participation in another interventional clinical research trial
11. Having cooperation and/or understanding that does not allow strict adherence to the conditions outlined in the protocol
12. Being under a legal protective measure (guardianship, tutorship, judicial safeguard)
13. Patient presenting with deep pelvic endometriosis or a fibroid
14. Being on anticoagulant treatment between Month -1 and Month 1.
15. Infection or inflammation at the injection site
16. Postmenopausal woman (defined as at least 12 months of amenorrhea not related to hormonal treatment)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the response (favorable versus unfavorable) to the Patient Global Impression of Improvement (PGI-I) questionnaire at 3 months after the intra-myometrial injection. The response is considered favorable when the PGI-I score is 1 or 2.

Secondary endpoints 15

1. Average and maximum intensity of dysmenorrhea evaluated using a Visual Analog Scale and duration (in days) during the last cycle before injection, then at 3 and 6 months.
2. Average and maximum intensity of pelvic pain outside of menstruation, evaluated using a Visual Analog Scale before injection, then at 1, 3, and 6 months, and duration (in days).
3. Average and maximum intensity of pain during the last sexual intercourse, evaluated using a Visual Analog Scale before injection, then at 1, 3, and 6 months.
4. Sexual function scale, Female Sexual Function Index (FSFI), evaluated before injection, then at 1, 3, and 6 months.
5. Central sensitization pain score, Convergences PP, evaluated before injection, then at 3 months
6. Higham score for evaluating menstrual blood loss, assessed before injection, then at 3 and 6 months. Duration (in days) of menstruation during the last cycle evaluated before injection, then at 3 and 6 months.
7. Global quality of life score SF-36 and specific quality of life score EHP-5, evaluated before injection, then at 1, 3, and 6 months.
8. Number of days of school or work absenteeism during the last month, assessed before injection, then at 1, 3, and 6 months
9. Anxiety score STAI-Y evaluated before injection and at 3 months. Depression score, Beck Depression Inventory (BDI-II), evaluated before injection and at 3 months.
10. Percentage of overall improvement (0-100%) evaluated at 1, 3, and 6 months. Patient Global Impression of Improvement (PGI-I) evaluated at 1 and 6 months. Patient’s willingness to undergo the intervention again (Yes/No) at 6 months and collection of justification.
11. Pain intensity experienced during the procedure and at 5 minutes, evaluated using a Visual Analog Scale
12. Adverse effects related to the injections collected in the immediate postoperative period, then at 1, 3, and 6 months
13. Occurrence of emergency consultations in the postoperative period, evaluated at 1 month
14. For the exploratory analysis of the MEOPA subgroup: primary endpoint, pain during the procedure, willingness to undergo the intervention again, adverse effects, and postoperative consultations
15. For the exploratory analysis of the hormonal treatment subgroup: all primary and secondary endpoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Claire CARDAILLAC

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Claire CARDAILLAC

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications