Botulinum Toxin Injection to Treat Diffuse Esophageal Spasm

Study Overview
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Brief Summary
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This study evaluates the effect of botulinum toxin 100 U or saline, injected endoscopically in the distal esophagus, on symptoms and manometry pattern in patients with diffuse esophageal spasm.

Detailed Description
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Patients are selected on the basis of a clinical diagnosis of diffuse esophageal spasm, based on endoscopy and manometry. This is a sham-controlled cross-over study of injection of botulinum toxin or saline, in randomized order, in the distal esophagus. All patients have undergone esophageal manometry which shows diffuse esophageal spasm, and a 24h pH monitoring/manometry to quantify acid reflux. All drugs prescribed to affect esophageal motility (nitrates, calcium antagonists) are stopped during the study. After randomisation, the patient will undergo standard esophageal manometry to assess baseline esophageal motility. On the same day the patient will be asked to fill out a set of symptom questionnaires including a dysphagia questionnaire. At endoscopy, the active treatment group receives 8 x 12.5 units, each in 0.5 ml, of botulinum toxin A which will be injected in the four quadrants of the esophagus at 2 and 5 cm above the lower esophageal sphincter. In the Sham group 8 * 0.5 ml of physiologic serum will be injected. The randomisation will be performed at the endoscopy unit by a nurse otherwise not involved in the protocol. After 1 month a stationary manometry and a new esophageal pH/manometry monitoring will be performed, followed by a second endoscopy with injection of saline or botulinum toxin in a cross-over mode. At the time of the second endoscopy each patient will fill out a dysphagia questionnaire. One month later, the dysphagia questionnaire is repeated. Subsequently, follow-up will occur at the outpatient clinic after 6 and 12 months, with follow-up dysphagia questionnaires but no additional manometries or endoscopies, unless the clinical status deteriorates.

Official Title
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Prospective Randomised Double-blind Sham Study on the Use of Botox for the Treatment of Diffuse Esophageal Spasm

Conditions
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Esophageal Spasm, Diffuse

Intervention / Treatment
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* Drug: Placebo
* Drug: Botulinum Toxin Type A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spastic motor disorder in the upper GI tract Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo arm: per-endoscopic injection of saline | Drug: Placebo<br>* Saline 4 ml<br>|
| Active Comparator: Botulinum toxin<br>Botulinum toxin (Botox) 100 u in 4 ml, injected per-endoscopically | Drug: Botulinum Toxin Type A<br>* per-endoscopic injection of 100 U of botulinum toxin dissolved in 4 ml of saline<br>* Other names: Botox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dysphagia severity score | the primary outcome variable is the symptom severity score in patients with diffuse esophageal spasm. | One month after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Manometry pattern | Pattern of contractions on stationary esophageal manometry | One month after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Weight loss, Dysphagia, Esophageal hypermotility, Chest Pain