Placebo Controlled Trial of Botulinum Toxin for Gastroparesis

NCT ID: NCT00372970

Last Updated: 2015-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2008-12-31

Brief 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.

Conditions

Gastroparesis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Botulinum Toxin A

200 U of Botox injected endoscopically into pylorus

Group Type: ACTIVE_COMPARATOR

Botulinum toxin A

Intervention Type: DRUG

200 U given by injection into the pylorus.

Placebo

saline into pylorus.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

saline injection into pylorus.

Interventions

Botulinum toxin A

200 U given by injection into the pylorus.

Intervention Type: DRUG

Placebo

saline injection into pylorus.

Intervention Type: DRUG

Other Intervention Names

Botox into pylorus; saline injection into pylorus

Eligibility Criteria

Inclusion Criteria

• Documented gastroparesis by radiologic study
• No ulcer disease
• Only surgery history must be either appendectomy or cholecystectomy
• No prior treatment with Botox

Exclusion Criteria

• Prior botox injection

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American College of Gastroenterology

OTHER

Sponsor Role: collaborator

Temple University

OTHER

Sponsor Role: lead

Responsible Party

Frank K. Friedenberg

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frank K Friedenberg, MD

Role: PRINCIPAL_INVESTIGATOR

Temple University

Locations

Temple University Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

References

Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008 Feb;103(2):416-23. doi: 10.1111/j.1572-0241.2007.01676.x. Epub 2007 Dec 5.

Reference Type: RESULT

PMID: 18070232 (View on PubMed)

Other Identifiers

4204

Identifier Type: -

Identifier Source: org_study_id