Topical Bethanechol for Improvement of Esophageal Dysmotility

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gregory Postma, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01031043
First received: December 10, 2009
Last updated: January 27, 2015
Last verified: January 2015
  Purpose

The purpose of this research project is to determine the effect of a drug called bethanechol on swallowing function in patients with Ineffective Esophageal Motility (IEM). This drug is FDA approved for use in treating other conditions, but not for the treatment of IEM. There is currently no approved therapy for the treatment of IEM. This information is important for the possible development of new ways of treating patients with IEM and for the effectiveness of topically applied Bethanechol on patients with IEM.


Condition Intervention Phase
Esophageal Dysmotility
Drug: Bethanechol
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Topical Bethanechol for Improvement of Esophageal Dysmotility: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Georgia Regents University:

Primary Outcome Measures:
  • Distal Contractile Integral [ Time Frame: Encounter 1 (day 1) and Encounter 2 (Month 14) ] [ Designated as safety issue: No ]
    The index of contractile strength of the esophageal smooth muscle. The range of the index being 0 mmHg *s*cm to >10,000 mmHg *s*cm where 0 represents no contractile strength. The index reflects the magnitude of distal esophageal contraction, taking into consideration the length, strength, and duration of the contraction.


Enrollment: 5
Study Start Date: November 2009
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topical Bethanechol
patients will be given either 5 mg (first phase) or 10 mg (second phase) of bethanechol in 1 ml of solution containing an absorption enhancer. Administration will be performed by throat spray device
Drug: Bethanechol
Taking part in this research study is voluntary. Patient may choose not to take part in this research study or may withdraw consent at any time. Their choice will not at any time affect the commitment of the health care providers to administer care. If the patient decides not to participate or withdraw from the study there will be no penalty or loss of benefits to which they are otherwise entitled.
Other Name: Urecholine

Detailed Description:

This is a pilot study, and as such is not necessarily expected to achieve statistical significance. A control group will not be used, again owing to the pilot nature of the study. Previous studies have demonstrated the safety of oral bethanechol. It has shown some efficacy in the treatment of gastroesophageal reflux in both adults and children1-8, and there is extensive preclinical data suggesting a beneficial effect for patients with IEM9-14. A single study15 of oral bethanechol in patients with IEM demonstrated a significant improvement in distal esophageal muscle contraction and bolus transit. This study, however measured esophageal function using an inferior method of manometry. The proposed study uses high-resolution manometry to measure the effects of oral bethanechol in patients with IEM, and will yield improved understanding of changes in esophageal function in real-time. The study intervention (oral bethanechol) will be a single-dose event (applied in two encounters), not an ongoing treatment intervention.

We will evaluate the effect of topically applied bethanechol on esophageal motility in a cohort (n=20) of patients with IEM. Presence of IEM will be defined using current criteria: esophageal contraction amplitude <30 mmHg either 5 or 10 cm above the lower esophageal sphincter, in 50% or more of saline swallows15, 16. We will perform high-resolution manometry (HRM) to establish a baseline in these patients. HRM is part of the cutting-edge technology available at the Medical College of Georgia Center for Voice and Swallowing Disorders (CVSD, part of the Department of Otolaryngology), and is used in the clinical evaluation of patients with dysphagia on a routine basis. Many patients with IEM referred to the CVSD will undergo high-resolution manometry during the course of their evaluation and treatment, regardless of inclusion in this study. The test consists of placement of a manometry catheter through the nasal cavity into the esophagus, much as a naso-gastric tube would be placed. After confirming proper placement of the catheter by manometry, the patient is asked to perform 10 swallows of a teaspoon (5ml) of water. The muscle contractions of the esophagus, including the upper and lower esophageal sphincters, are then recorded in real-time along the entire length of the catheter for the duration of the swallow. This allows measurement and analysis of not only isolated contraction events, but also the entire swallow as it propagates down the esophagus.

Following establishment of baseline esophageal function, patients will be given either 5 mg (first phase) or 10 mg (second phase) of bethanechol in 1 ml of solution containing an absorption enhancer. Administration will be performed by throat spray device. The composition of the delivery solution is proprietary. Since bethanechol is a quaternary amine known to have less than 1 % topical absorbance, an absorption enhancer is necessary to aid in this process. The choice of an appropriate FDA approved absorption enhancer is what makes this preparation unique. The preparation also contains thickening agents that allow it to remain where sprayed to enhance absorption.

After waiting 10 minutes, patients will then undergo a post-treatment HRM to establish treatment effect. The manometry catheter will be left in place during the entire encounter, thus requiring only the single placement of the catheter per sessions. Two sessions will be required to establish dose escalation effect.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Any adult patient treated at the Medical College of Georgia, with severe IEM as defined using current criteria: esophageal contraction amplitude <30 mmHg either 5 or 10 cm above the lower esophageal sphincter, in 50% or more of saline swallows.

Exclusion Criteria:

  • Patients with severe comorbidities (including uncontrolled hypertension, severe coronary artery disease, and uncontrolled diabetes) will be specifically excluded from the study.
  • Additionally, the use of bethanechol (as well as all other muscarinic receptor agonists) is contraindicated in patients with asthma, coronary insufficiency, peptic ulcers, Parkinson's disease, seizure disorder, recent gastrointestinal surgery, and hyperthyroidism. As such any patient with these disorders will be specifically excluded from this study.
  • Women of childbearing age will also be specifically excluded (Bethanechol is listed as a pregnancy class C drug).
  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: NCT01031043

Locations
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
Sponsors and Collaborators
Georgia Regents University
Investigators
Principal Investigator: Gregory N Postma, MD Georgia Regents University
  More Information

No publications provided

Responsible Party: Gregory Postma, Professor, Georgia Regents University
ClinicalTrials.gov Identifier: NCT01031043     History of Changes
Other Study ID Numbers: 09-03-244
Study First Received: December 10, 2009
Results First Received: January 12, 2015
Last Updated: January 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgia Regents University:
IEM

Additional relevant MeSH terms:
Esophageal Motility Disorders
Esophageal Spasm, Diffuse
Deglutition Disorders
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Bethanechol
Autonomic Agents
Cholinergic Agents
Cholinergic Agonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Agonists
Neurotransmitter Agents
Parasympathomimetics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2015