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Placebo Controlled Trial of Botulinum Toxin for Gastroparesis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00372970
Recruitment Status : Completed
First Posted : September 7, 2006
Results First Posted : June 9, 2015
Last Update Posted : June 9, 2015
Sponsor:
Collaborator:
American College of Gastroenterology
Information provided by (Responsible Party):
Frank K. Friedenberg, Temple University

Tracking Information
First Submitted Date  ICMJE September 5, 2006
First Posted Date  ICMJE September 7, 2006
Results First Submitted Date  ICMJE April 16, 2015
Results First Posted Date  ICMJE June 9, 2015
Last Update Posted Date June 9, 2015
Study Start Date  ICMJE July 2003
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2015)
Symptom Response as Assessed by the Gastroparesis Cardinal Symptom Index. [ Time Frame: 1 month ]
Scale for GI symptoms related to gastroparesis. For this we will use the gastroparesis cardinal symptom index (GCSI). The GCSI is based on three subscales: post-prandial fullness/early satiety (4 items); nausea/vomiting (3 items), and bloating (2 items). Scores range from 0-5 for the nine items and an asymptomatic patient would have a score of 0 with a highly symptomatic patient having a score of 45. For this study the score had to be >=27. In a previous study internal consistency reliability was 0.84 for the GCSI total score and ranged from 0.83 to 0.85 for the subscale scores. Two week test retest reliability was 0.76 for the total score and ranged from 0.68 to 0.81 for subscale scores.
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2006)
Symptom Response as Assessed by the Gastroparesis Cardinal Symptom Index.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2006)
gastric emptying changes as assessed by scintigraphy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Placebo Controlled Trial of Botulinum Toxin for Gastroparesis
Official Title  ICMJE Randomized Placebo-Controlled Double Blind Study of Botulinum Toxin Versus Placebo for the Treatment of Gastroparesis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Gastroparesis
Intervention  ICMJE
  • Drug: Botulinum toxin A
    200 U given by injection into the pylorus.
    Other Name: Botox into pylorus
  • Drug: Placebo
    saline injection into pylorus.
    Other Name: saline injection into pylorus
Study Arms  ICMJE
  • Active Comparator: Botulinum Toxin A
    200 U of Botox injected endoscopically into pylorus
    Intervention: Drug: Botulinum toxin A
  • Placebo Comparator: Placebo
    saline into pylorus.
    Intervention: Drug: Placebo
Publications * 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. Epub 2007 Dec 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2015)
32
Original Enrollment  ICMJE
 (submitted: September 6, 2006)
30
Actual Study Completion Date  ICMJE December 2008
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00372970
Other Study ID Numbers  ICMJE 4204
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Frank K. Friedenberg, Temple University
Study Sponsor  ICMJE Temple University
Collaborators  ICMJE American College of Gastroenterology
Investigators  ICMJE
Principal Investigator: Frank K Friedenberg, MD Temple University
PRS Account Temple University
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP