Botulinum Toxin Injection in Hypercontractile Esophagus (TIBOH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01955174
First received: September 27, 2013
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Esophageal Hypercontractile Motility Disorders
Drug: Endoscopic injection of botulinum toxin in the esophageal muscle
Other: Upper gastro-intestinal endoscopy without any injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Clinical response [ Time Frame: 3 months after Botulinum toxin injection or sham procedure ] [ Designated as safety issue: No ]
    Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2


Secondary Outcome Measures:
  • Clinical symptoms improvement [ Time Frame: 12 months after Botulinum toxin injection or sham procedure ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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)


Estimated Enrollment: 28
Study Start Date: August 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Botulinum toxin
Esophageal endoscopic injection of botulinum toxin
Drug: 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: Upper gastro-intestinal endoscopy without any injection

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01955174

Contacts
Contact: Sophie MARJOUX, MD 472 11 01 36 ext +33 sophie.marjoux@chu-lyon.fr
Contact: François MION, MD francois.mion@chu-lyon.fr

Locations
France
Service d'Hépato-Gastro-Entérologie - Hôpital Saint André - CHU de Bordeaux Recruiting
Bordeaux Cedex, France, 33075
Contact: Franck ZERBIB, MD    556 79 58 06 ext +33    frank.zerbib@chu-bordeaux.fr   
Principal Investigator: Franck ZERBIB, MD         
Service d'Exploration Fonctionnelle Digestive - Hôpital Edouard Herriot Pavillon H 5 - Hospices Civils de Lyon Recruiting
LYON Cedex 03, France, 69437
Contact: Sophie MARJOUX, MD    472 11 01 36 ext +33    sophie.marjoux@chu-lyon.fr   
Contact: François MION, MD       francois.mion@chu-lyon.fr   
Principal Investigator: Sophie MARJOUX, MD         
Sponsors and Collaborators
Hospices Civils de Lyon
  More Information

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01955174     History of Changes
Other Study ID Numbers: 2012.779
Study First Received: September 27, 2013
Last Updated: January 14, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Hospices Civils de Lyon:
Botulinum toxin
Esophageal motility disorder
Distal esophageal spasm

Additional relevant MeSH terms:
Botulinum Toxins
Esophageal Motility Disorders
Esophageal Spasm, Diffuse
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014