Placebo Controlled Trial of Botulinum Toxin for Gastroparesis

This study has been completed.
Sponsor:
Collaborator:
American College of Gastroenterology
Information provided by (Responsible Party):
Frank K. Friedenberg, Temple University
ClinicalTrials.gov Identifier:
NCT00372970
First received: September 5, 2006
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Gastroparesis
Drug: Botulinum toxin type A
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Placebo-Controlled Double Blind Study of Botulinum Toxin Versus Placebo for the Treatment of Gastroparesis

Resource links provided by NLM:


Further study details as provided by Temple University:

Primary Outcome Measures:
  • symptom response as assessed by the gastroparesis cardinal symptom index. [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • gastric emptying changes as assessed by scintigraphy. [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: July 2003
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Botulinum toxin type A
    200 U given by injection into the pylorus.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00372970

Locations
United States, Pennsylvania
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
Sponsors and Collaborators
Temple University
American College of Gastroenterology
Investigators
Principal Investigator: Frank K Friedenberg, MD Temple University
  More Information

Additional Information:
No publications provided

Responsible Party: Frank K. Friedenberg, Professor of Medicine, Temple University
ClinicalTrials.gov Identifier: NCT00372970     History of Changes
Other Study ID Numbers: 4204
Study First Received: September 5, 2006
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Temple University:
gastroparesis
vomiting
nausea
bloating
dyspepsia

Additional relevant MeSH terms:
Gastroparesis
Digestive System Diseases
Gastrointestinal Diseases
Neurologic Manifestations
Paralysis
Signs and Symptoms
Stomach Diseases
Botulinum Toxins
Botulinum Toxins, Type A
Anti-Dyskinesia Agents
Central Nervous System Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014