Botulinum Toxin Injection in Hypercontractile Esophagus

Nutcracker Oesophagus Clinical Trial

— TIBOH  

Official title:

Endoscopic Injection of Botulinum Toxin in Patients With Hypercontractile Esophageal Motility Disorders: a Prospective, Randomized, Double-blind, Controlled Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01955174
• Other study ID #: 2012.779
• Status: Completed
• Phase: Phase 2
• Start date: August 2013
• Est. completion date: February 2018

Study information

• Verified date: May 2018
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 2018
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Esophageal Motility Disorders
• Esophageal Spasm, Diffuse
• Nutcracker Oesophagus

Intervention

Drug:
• Esophageal endoscopic injection of botulinum toxin
Endoscopic injection of botulinum toxin in the esophageal muscle : one hundred units of type A botulinum toxin (Botox®, Allergan) diluted in 10 mL of normal saline and injected at the lower third of the esophageal wall in 10 sites between 2 and 10 cm above the Z-line.

Other:
• No injection of botulinum toxin
Upper gastro-intestinal endoscopy without any injection

Locations

Country	Name	City	State
France	Service d'Hépato-Gastro-Entérologie et Oncologie Digestive- Hôpital Haut Lévêque - CHU de Bordeaux	Bordeaux Cedex
France	Service d'Exploration Fonctionnelle Digestive - Hôpital Edouard Herriot Pavillon H 5 - Hospices Civils de Lyon	LYON Cedex 03

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response	Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2	3 months after Botulinum toxin injection or sham procedure
Secondary	Clinical symptoms improvement	Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2	12 months after Botulinum toxin injection or sham procedure
Secondary	Clinical symptoms improvement	Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2	After 2 procedures of Botulinum toxin injection or sham procedure
Secondary	Safety	Evaluation of chest pain with numerical scale from 0 (no pain) to 10 (worst pain) along the 15 days following the procedure, and percentage of patients experimenting adverse events.	Days 1- 7 after procedure. Month 1,3, 4, 6 and 12 after procedure
Secondary	Quality of life improvement	Evaluation of the quality of life with the Gastrointestinal Quality of Life Index (GIQLI)	At the first visit, 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Secondary	Weight gain	Evaluation of weight in kg	3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Secondary	Modification of HRM pattern	Change towards normal of specific HRM metrics: decrease of mean Distal Contratile Integral, disappearance of contraction with DCI > 8 000, increase of the % of contractions with normal Distal Latency	3 and 12 months after the first procedure (botulinum toxin injection or sham procedure)
Secondary	Clinical and paraclinical characteristics of responders versus non-responders	Age, sex, BMI, associated diseases, esophageal motility disorder according to the Chicago classification, associated medications, severity of symptoms at baseline (Eckardt) score, impairment of QOL at baseline (GIQLI score)	12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)