Botulinum Toxin Injection in Hypercontractile Esophagus (TIBOH)
|Nutcracker Oesophagus||Drug: Esophageal endoscopic injection of botulinum toxin Other: No injection of botulinum toxin||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Endoscopic Injection of Botulinum Toxin in Patients With Hypercontractile Esophageal Motility Disorders: a Prospective, Randomized, Double-blind, Controlled Study|
- Clinical response [ Time Frame: 3 months after Botulinum toxin injection or sham procedure ]Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2
- Clinical symptoms improvement [ Time Frame: 12 months after Botulinum toxin injection or sham procedure ]Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2
- Clinical symptoms improvement [ Time Frame: After 2 procedures of Botulinum toxin injection or sham procedure ]Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2
- Safety [ Time Frame: Days 1- 7 after procedure. Month 1,3, 4, 6 and 12 after procedure ]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.
- Quality of life improvement [ Time Frame: At the first visit, 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure) ]Evaluation of the quality of life with the Gastrointestinal Quality of Life Index (GIQLI)
- Weight gain [ Time Frame: 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure) ]Evaluation of weight in kg
- Modification of HRM pattern [ Time Frame: 3 and 12 months after the first procedure (botulinum toxin injection or sham procedure) ]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
- Clinical and paraclinical characteristics of responders versus non-responders [ Time Frame: 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure) ]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)
|Actual Study Start Date:||August 2013|
|Estimated Study Completion Date:||April 2018|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
Experimental: Botulinum toxin injection
Esophageal endoscopic injection of botulinum toxin
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.
Sham Comparator: No injection
No injection of botulinum toxin
Other: No injection of botulinum toxin
Upper gastro-intestinal endoscopy without any injection
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01955174
|Service d'Hépato-Gastro-Entérologie et Oncologie Digestive- Hôpital Haut Lévêque - CHU de Bordeaux|
|Bordeaux Cedex, France, 33075|
|Service d'Exploration Fonctionnelle Digestive - Hôpital Edouard Herriot Pavillon H 5 - Hospices Civils de Lyon|
|LYON Cedex 03, France, 69437|
|Principal Investigator:||François MION, MD||Hospices Civils de Lyon|