Clinical Trial: Botulinum Toxin Injection in Hypercontractile Esophagus

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 Summary:

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 scor
Sponsor: Hospices Civils de Lyon

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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)


Original Secondary Outcome: Same as current

Information By: Hospices Civils de Lyon

Dates:
Date Received: September 27, 2013
Date Started: August 2013
Date Completion: April 2018
Last Updated: August 5, 2016
Last Verified: August 2016