Is Botulinum Toxin Effective Treatment for Delayed Gastric Emptying?

David A. Johnson, MD, FACG, FACP


April 08, 2008

Botulinum Toxin A for the Treatment of Delayed Gastric Emptying

Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB
Am J Gastroenterol. 2008;103:416-423

Gastroparesis is a condition of delayed gastric emptying. Most commonly, this condition is due to diabetic, postsurgical, postviral, or idiopathic causes. Estimates of prevalence suggest that this condition occurs in 30% to 50% of patients with type 1 diabetes, in 16% to 30% of type 2 diabetics, and in 20% to 40% of patients with functional dyspepsia.[1] A recent report provided evidence that there is an increasing prevalence of hospitalizations associated with this condition.[1] Furthermore, this report showed that a primary diagnosis of gastroparesis has longer associated hospitalizations and higher hospital-related costs compared with other common upper gastrointestinal diseases (eg, gastroesophageal reflux, gastric ulcer, gastritis, nonspecific nausea/vomiting). Thus, given that gastroparesis is a prevalent disease with a significant economic impact, adequate treatment is extremely important.

Unfortunately, treatment options for gastroparesis are extremely limited. Prokinetic agents have limited success due to side effects (eg, cardiac issues associated with cisapride [available under protocol]; neurologic issues and tachyphylaxis issues associated with metoclopramide; antibiotic resistance/bacterial overgrowth associated with erythromycin; and availability issues for domperidone, which is not marketed in the United States). Of note, none of these medical therapies is approved by the US Food and Drug Administration for the treatment of gastroparesis.[2] The efficacy of gastric pacing has been variable. Moreover, there is extremely limited access to this technology, which is only offered by a few tertiary referral centers in the United States.

Given the challenges associated with the treatment of gastroparesis, there has been considerable attention and interest in other therapeutic approaches. The use of botulinum toxin A has been reported to be of some benefit in a number of observational studies, demonstrating improvement in both gastric emptying and/or symptoms.[3] Unfortunately, there has been no controlled trial to demonstrate the efficacy of this intervention.

The present study was a single-center, prospective, randomized, concealed allocation, controlled trial involving 32 patients with documented symptomatic gastroparesis. All patients had a demonstrated abnormality defined by gastric emptying test as well as by the Gastroparesis Cardinal Symptom Index (GCSI) score. The use of prokinetics was discontinued in all cases prior to entry into the screening phase of the study. Patients were randomized to receive intrapyloric botulinum toxin (200 units) injection (n=16) or saline placebo (n=16). The primary endpoint was a symptomatic improvement of 9 points or more on the GCSI. Sample size was justified, and there was no drop-out during the study.

After 1 month, symptomatic improvement was evident in 37.5% of patients randomized to botulinum toxin compared with 56.3% randomized to placebo. There were no significant differences in gastric emptying.

Clearly, many physicians in clinical gastroenterology practice use, or have tried, or have had patient queries about pyloric injection of botulinum toxin for treatment of gastroparesis. Data from previous uncontrolled trials have certainly supported the enthusiasm associated with this therapeutic approach. Unfortunately, on the basis of findings from this present study, support for this enthusiasm is not evident.

These results are consistent with those from 2 previous placebo-controlled studies (N=12[4] and N=18[5]) from the same institution. Although there were differences in the methodology used in the earlier studies, the take-home message is the same: there is currently no scientific support to justify the use of intrapyloric injection of botulinum toxin in patients with gastroparesis. There are some potential issues related to the present study that warrant mention. One could argue about the power calculations that assumed a high estimated response rate (80%). Although this was made on the basis of prior uncontrolled study response data showing an approximate 70% response rate, this estimate may have still been inaccurate. Second, the successful injection of botulinum toxin into the muscular portion of the pylorus for the treatment of gastroparesis may be harder to define than successful injection for achalasia treatment (eg, which involves injection of the lower esophageal sphincter). Endoscopic ultrasound-directed injection of the pylorus may be more helpful and then may conceivably have an impact on the outcome.

The take-home message from this study is clear: Although there has been considerable "hope and hype" regarding this potential intervention, at this time, the use of intrapyloric injection of botulinum toxin cannot be justified in routine clinical practice in patients with gastroparesis. Clearly, there is a need for additional studies involving larger numbers of patients and using a more specific, standardized, and directed injection protocol.



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