Clinical trial NCT01955174: Botulinum Toxin Injection in Hypercontractile Esophagus
Official title: Endoscopic Injection of Botulinum Toxin in Patients With Hypercontractile Esophageal Motility Disorders: a Prospective, Randomized, Double-blind, Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nutcracker Oesophagus
Keywords: Botulinum toxin
Esophageal motility disorder
Distal esophageal spasm
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2013-10-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the efficacy and the safety of endoscopic injection of 100 IU of botulinum toxin (BTX) in the distal esophagus in patients with symptoms related to hypercontractile esophageal motility disorders.

Detailed description: Eligible patients will present chest pain and/or dysphagia related to the following hypercontractile esophageal motility disorders: distal esophageal spasm, jackhammer esophagus, nutcracker esophagus or type III achalasia with normalization of the integrated relaxation pressure after treatment, based on the Chicago classification of esophageal motility disorders for high resolution manometry (HRM). Upper gastrointestinal endoscopy and barium swallow will be performed before BTX injection to eliminate secondary disorders.

This is a prospective, randomized, double blind, controlled trial comparing BTX injection to sham procedure (absence of injection, the clinical team performing the follow-up will not be aware of the result of the randomization).

Drugs which could affect esophageal motility (nitrates and calcium channel blockers) will be stopped during the study.

Included patients will undergo esophageal endoscopic ultrasound examination (EEUS) and upper gastrointestinal endoscopy under general anesthesia. In absence of contraindications, patients will be randomized in two arms: BTX injection or no injection. The active treatment group will receive 100 units of type A BTX (Botox®, Allergan) diluted in 10 mL of saline serum; BTX will be injected into the lower third of the esophageal wall in 10 sites between 2 and 10 cm above the squamo-columnar junction. The control arm will receive no injection after the EEUS and upper GI endoscopy (sham procedure).

Clinical response will be assessed based on the evolution of the Eckardt score, a quality of life score (Gastrointestinal Quality of Life Index (GIQLI), and weight gain. A significant clinical response will be defined as an Eckardt score \< 3 (together with individual scores \< 2). Manometry patterns will be compared before and after the procedure. Safety will be monitored based on the occurrence of chest pain scored on a Likert scale and occurrence of adverse events.

Follow-up clinical evaluation will be performed 1 and 2 months after the procedure. A second esophageal HRM will be realized 3 months after the procedure, followed by endoscopic BTX injection in case of non-response and two monthly visits.

Follow-up visits will be done 6 and 12 months after the first procedure. An additional HRM will be performed at 12 months.

Eligibility criteria: Inclusion Criteria:

* Patient with non-cardiac chest pain and/or dysphagia with global Eckardt score strictly above 3 points or equal to 3 only for " chest pain " or " dysphagia " - Hypercontractile esophagus with normal esogastric junction relaxation based on the Chicago classification in high resolution manometry
* Man or woman 18-year old or older
* Normal upper gastrointestinal endoscopy within one year before inclusion
* Barium swallow without argument for external compression
* Effective form of birth control (if applicable)
* Signed written informed consent form voluntarily
* Patient with health insurance

Exclusion Criteria:

* Man or woman under 18-year old
* Past history of eso-gastric surgery
* Evolutive cancer or coagulation disorders
* Absence of effective form of birth control (if applicable)
* Pregnant woman or woman who plans to become pregnant during the expected length of the study
* Breastfeeding woman
* Allergy to botulinum toxin or excipients
* Myasthenia
* Aminoglycoside treatment
* Endoscopic contraindication prior to the study
* Endoscopic contraindication during the study
* Psychiatric or addictive disease which could affect compliance to the constraints of the study
* Patient refusing to participate to the study
* Language barrier limiting the understanding of the study
* Incapability to give consent
* Concomitant participation to another research study
* No written consent form

Primary outcomes:
measure: Clinical response
timeFrame: 3 months after Botulinum toxin injection or sham procedure
Secondary outcomes:
measure: Clinical symptoms improvement
timeFrame: 12 months after Botulinum toxin injection or sham procedure
measure: Clinical symptoms improvement
timeFrame: After 2 procedures of Botulinum toxin injection or sham procedure
measure: Safety
timeFrame: Days 1- 7 after procedure. Month 1,3, 4, 6 and 12 after procedure
measure: Quality of life improvement
timeFrame: At the first visit, 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
measure: Weight gain
timeFrame: 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
measure: Modification of HRM pattern
timeFrame: 3 and 12 months after the first procedure (botulinum toxin injection or sham procedure)
measure: Clinical and paraclinical characteristics of responders versus non-responders
timeFrame: 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Other outcomes:
Locations:
city: Bordeaux Cedex
country: France
facility: Service d'Hépato-Gastro-Entérologie et Oncologie Digestive- Hôpital Haut Lévêque - CHU de Bordeaux
city: LYON Cedex 03
country: France
facility: Service d'Exploration Fonctionnelle Digestive - Hôpital Edouard Herriot Pavillon H 5 - Hospices Civils de Lyon
Study officials:
affiliation: Hospices Civils de Lyon
name: François MION, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mion F, Marjoux S, Subtil F, Pioche M, Rivory J, Roman S, Zerbib F. Botulinum toxin for the treatment of hypercontractile esophagus: Results of a double-blind randomized sham-controlled study. Neurogastroenterol Motil. 2019 May;31(5):e13587. doi: 10.1111/nmo.13587. Epub 2019 Apr 11.