Clinical trial NCT03496649: Pubalgia and Adductor Tendinopathies Refractory to Medical Treatment
Official title: Feasability Study on the Use of Botulinum Toxin A in Primary Adductor Tendinopathies Refractory to Medical Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Groin Injury
Tendinopathy
Keywords: Primary Adductor tendinopathies
Pubalgia
Botulinum toxin type A
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Ipsen
First posted: 2018-04-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Pubalgia is a pain syndrome located in the groin area. This syndrome is mainly described in young male athletes and typically affect the superficial muscles defining the boundaries of the femoral triangle, i.e. gracilis, pectineus, adductor brevis and especially adductor longus, and less commonly the deep muscles.

Clinically, the pain is located in the inner aspect of the thigh, where the tendons attach onto the pubic symphysis. It is usually unilateral, and sometimes associated with neuropathic pain suggestive of obturator nerve irritation.

There is no official recommendation or expert consensus on the management of pubalgia. However, a few protocols recommend a period of rest with Non-Inflammatory Anti-Steroidien Drugs (NSAIDs), icing and massages, as well as rehabilitation with passive stretching and muscle reinforcement.

The use of botulinum toxin type A could be an option in cases of treatment failure. However, a feasibility study must be performed beforehand, and if results are positive, a controlled study on a larger cohort could be conducted.

The major potential impact is a great effective pain relief for patients with neurological diseases.

Detailed description: The incidence of pubalgia in the literature varies, with large series reporting an incidence close to 5-10%, representing 15 to 18% of all injuries.

Recurrences are also common, affecting 30 to 35% of cases.

Once other differential diagnoses (such as spondylarthropathy, colorectal cancer, kidney disease...) have been ruled out, athletic pubalgia is typically divided into three main categories based on the site of the injury:

* Abdominal wall, the most common form, representing 38 to 50% of all cases;
* Pubic symphysis due to osteoarthropathy of the pubic bone caused by repetitive stress injury, accounting for 10 to 15% of all cases of pubalgia;
* Adductor tendons, on which this study focuses, representing 22 to 38% of all cases of pubalgia, caused by repetitive tractions on the tendon insertions.

There is no official recommendation or expert consensus on the management of pubalgia. However, a few protocols recommend a period of rest with Non-Inflammatory Anti-Steroidien Drugs (NSAIDs), icing and massages, as well as rehabilitation with passive stretching and muscle reinforcement.

Neuromuscular reprogramming is then performed to stabilise the pelvis, followed by a progressive resumption of sporting activities, guided by the pain level.

Generally, 70 to 85% of patients are able to resume their sporting activities with this management protocol.

In 15 to 20% of cases of essential adductor tendinopathy, symptoms do not improve and the only currently validated solution is then a tenotomy, sometimes combined with partial tendon release in recurring cases.

Recent studies showed that the use of botulinum toxin type A (BTA) produces fairly positive results in chronic tendinopathies, such as epicondylitis. However, the efficacy of BTA injections in adductor tendinopathies has not been demonstrated consistently and a feasibility study must be conducted to address this question.

The hypothetical benefit of BTA in adductor tendinopathies is based on the toxin's known effects:

1. a purely analgesic effect, which reduces pain in the injected area within a few days. This type of chronic tendinopathy does not involve inflammation. The pain in such cases is most likely due to the action of neurotransmitters such as substance P and calcitonin gene-related peptide (CGRP). As BTA is known to inhibit the secretion of these neurotransmitters, this mechanism could explain the toxin's specific analgesic effect.
2. a muscle relaxant effect due to its action on the motor endplate, which reaches its maximum 6 weeks after the injection, and lasts 3 to 6 months.

The resulting muscle relaxation helps improve healing of the damaged tendon, and provides sustained analgesia.

A series including 39 cases showed that botulinum toxin is effective on hip adductor muscles following total hip arthroplasty, providing reduced muscle contracture and improved hip mobility without side effects.

The use of botulinum toxin type A could be an option in cases of treatment failure. However, a feasibility study must be performed beforehand, and if results are positive, a study on a larger cohort could be conducted.

Eligibility criteria: Inclusion Criteria:

* Male or female patient 18 to 65 years old
* Patient with episode of adductor tendinopathy, refractory to appropriate medical treatment lasting 3 months
* Tendinopathy confirmed by clinical investigation, echography and MRI.
* Patient naïve to intramuscular botulinum toxin injections
* Patient able to self-evaluate pain on a VAS
* Intensity of exercise-induced pain \> 5 on a VAS of 10
* Patient able to provide a signed informed consent freely for the study protocol and data collection

Exclusion Criteria:

* Subject participating or having participated in the last 3 months in another study which could interfere with the objective of the study
* Neuralgia
* Acute muscle injury
* Progressive disease at the time of inclusion
* Anticoagulant treatment: heparin administered with an electrical syringe or AVK therapy with effective doses

Exclusion criteria related to Dysport injection (botulinum toxin type A) :

* Known hypersensitivity to botulinum toxin type A or to any of the components in the formulation (20% human albumin solution, lactose monohydrate)
* Subject with a significant deficit of clinical or subclinical neuromuscular transmission (myasthenia or Lambert-Eaton syndrome)
* Treatment that directly or indirectly interferes with neuromuscular transmission (aminoglycosides, curare, anticholinesterase, aminoquinoline, cyclosporine, etc.)
* Previous surgery with curarisation less than a month ago
* History of neuromuscular disorders
* Pregnant or breastfeeding woman
* Women of child-bearing potential not using contraceptive methods during the study duration

Primary outcomes:
measure: Proportion of patients with a pain reduction (VAS)
timeFrame: Between Day 80 and Day 90
Secondary outcomes:
measure: Exercise-induced pain intensity (VAS)
timeFrame: Daily between Day 0 and Day 90
measure: Pain relief
timeFrame: On Day 30 and Day 90
measure: Goal Attainment Scaling (GAS)
timeFrame: On Day 30 and Day 90
measure: Blazina clinical classification system
timeFrame: On Day 30 and Day 90
measure: Adductor strength
timeFrame: On Day 30 and Day 90
measure: Cure rate based on patients' self-evaluation
timeFrame: On Day 30 and Day 90
measure: Cure rate based on physician's evaluation
timeFrame: On Day 30 and Day 90
measure: Treatment
timeFrame: On Day 30 and Day 90
measure: Pain diary
timeFrame: On Day 30 and Day 90
measure: HAGOS self-reported questionnaire
timeFrame: On Day 30 and Day 90
measure: Tolerance
timeFrame: Day 1, Day 7, Day 14, Day 30, Day 90
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
Study officials:
References: