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

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.