Esophageal Dysmotility Clinical Trial
Official title:
Topical Bethanechol for Improvement of Esophageal Dysmotility: A Pilot Study
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.
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.
;
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT03604523 -
Esophageal Dysmotility - Prospective Study Evaluating Methods for Esophageal Dilation
|
N/A |