- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01955174
Botulinum Toxin Injection in Hypercontractile Esophagus (TIBOH)
Endoscopic Injection of Botulinum Toxin in Patients With Hypercontractile Esophageal Motility Disorders: a Prospective, Randomized, Double-blind, Controlled Study
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Bordeaux Cedex, France, 33075
- Service d'Hépato-Gastro-Entérologie et Oncologie Digestive- Hôpital Haut Lévêque - CHU de Bordeaux
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LYON Cedex 03, France, 69437
- Service d'Exploration Fonctionnelle Digestive - Hôpital Edouard Herriot Pavillon H 5 - Hospices Civils de Lyon
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Botulinum toxin injection
Esophageal endoscopic injection of botulinum toxin
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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
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Upper gastro-intestinal endoscopy without any injection
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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3 months after Botulinum toxin injection or sham procedure
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
12 months after Botulinum toxin injection or sham procedure
|
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
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After 2 procedures of Botulinum toxin injection or sham procedure
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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.
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Days 1- 7 after procedure. Month 1,3, 4, 6 and 12 after procedure
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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)
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Evaluation of the quality of life with the Gastrointestinal Quality of Life Index (GIQLI)
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At the first visit, 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
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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
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3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
|
Modification of HRM pattern
Time Frame: 3 and 12 months after the first procedure (botulinum toxin injection or sham procedure)
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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
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3 and 12 months after the first procedure (botulinum toxin injection or sham procedure)
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Clinical and paraclinical characteristics of responders versus non-responders
Time Frame: 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
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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)
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12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: François MION, MD, Hospices Civils de Lyon
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Gastrointestinal Diseases
- Deglutition Disorders
- Esophageal Diseases
- Esophageal Motility Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Cholinergic Agents
- Membrane Transport Modulators
- Acetylcholine Release Inhibitors
- Botulinum Toxins
Other Study ID Numbers
- 2012.779
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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