Placebo Controlled Trial of Botulinum Toxin for Gastroparesis
Condition: Gastroparesis
MeSH terms: Gastroparesis
Study type: Interventional

Summary: 
      It is hypothesized that in some patients with gastroparesis increased pyloric tone may be a
      contributing feature. Botox relaxes the pylorus so that food can empty the stomach more
      rapidly. Lesser quality studies have shown that this treatment works in about 40% of
      patients, and relieves symptoms for up to 3 months. This study compares this treatment to
      placebo (saline) injection. After a 1 month period patients may elect to receive open label
      botox who have not received relief from their first injection. Patients symptoms and gastric
      emptying are followed for 1 year.
    

Detailed description: 
      Patients with gastroparesis, or delayed gastric emptying, present with early satiety,
      postprandial bloating, nausea, vomiting, and abdominal pain or discomfort.1 Gastric emptying
      is a highly regulated process reflecting the integration of propulsive forces generated by
      proximal fundic tone and distal antral contractions with the resistance of the pyloric
      sphincter. Antral hypomotility as well as increased gastric outlet resistance due to pyloric
      dysfunction or pylorospasm appear to be important physiologic disturbances in
      gastroparesis.2-4 Current treatment for gastroparesis employs prokinetic agents that increase
      antral contractility and accelerate gastric emptying.5 Unfortunately, prokinetic agents have
      limited efficacy and trials of these agents have suffered from significant methodological
      flaws.6 Troublesome side effects such as cardiac arrhythmias in the case of cisapride
      (Propulsid, Janssen Pharmaceutica) and extrapyramidal symptoms and sedation in the case of
      metoclopramide (Reglan, A.H. Robins) have limited the usefulness of these agents.7
      Domperidone may be effective for treating symptoms of gastroparesis, however it is
      unavailable in the U.S.8

      Botulinum toxin (Botox, Allergan) is an inhibitor of cholinergic neuromuscular transmission
      and has been used to treat spastic disorders of both striated and smooth muscles by local
      injection into affected muscles.9 Previous published work from our institution demonstrated
      that injection of botulinum toxin into the pylorus improved gastric emptying and reduces
      symptoms in idiopathic gastroparesis.10 In our open label study, patients had a 38% reduction
      in gastroparesis symptoms when interviewed 4 weeks after injection. Seventy percent of
      patients had improved gastric emptying. No immediate or short term (within 6 months) untoward
      events occurred in our study. The beneficial effect of botulinum toxin injection was
      suggested to be through decreasing pyloric resistance; however, manometric analysis of this
      region was not performed. Our results are similar to those seen in other studies that have
      demonstrated accelerated gastric emptying in response to pyloric botulinum toxin
      injection.11-13 These studies have included groups of patients with both idiopathic and
      diabetic gastroparesis. Unfortunately, in all studies, the patient groups have been very
      small and the study design has been open label that might bias results in favor of a positive
      response. In addition, follow-up has been for only 6 months.

      Despite limited data, many gastroenterologists are now using botulinum toxin injection for
      the treatment of gastroparesis outside the context of clinical research studies. We are
      concerned that this practice may be increasing nationwide without definitive proof of
      efficacy. A randomized, placebo-controlled trial is necessary to establish the usefulness of
      pyloric botulinum toxin injection for gastroparesis. Botulinum toxin therapy is expensive and
      may not be efficacious. In addition, if efficacious, the mechanism by which botulinum toxin
      improves gastric emptying needs to be studied. This research protocol will answer several
      questions concerning this potentially useful therapy for gastroparesis.
    

Intervention name(s): Botulinum toxin A; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 200 U given by injection into the pylorus.; saline injection into pylorus.
Other intervention name(s): Botox into pylorus; saline injection into pylorus
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: gastroparesis; vomiting; nausea; bloating; dyspepsia