Clinical Trial: Transdermal Administration of a Prokinetic Agent for Bowel Evacuation in Persons With SCI

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Novel Application of Iontophoresis in the Transcutaneous Delivery of a Prokinetic Agent for the Promotion of Bowel Evacuation

Brief Summary:

Bowel care (BC) is a time-consuming and cumbersome activity of daily living for most individuals with SCI. Previous studies have reported that the average time to complete a BC routine is 45 minutes; 10-20% of SCI individuals report BC routines lasting for more than 1 hour. In past studies, the investigators have shown that a medication called neostigmine (NEO) combined with a medication called glycopyrrolate (GLY) can increase bowel activity and thus, promote bowel movement. The investigators have successfully used this medication with traditional and novel methods of colonoscopic preparations, and have shown that it improves the quality of these preparations. In this Phase I, proof of concept pilot study, the investigators propose to study the effectiveness of this medicine when it is delivered through the skin. In order to make delivery more efficient, the investigators will be using a technique called iontophoresis, which uses a mild electric current to drive the drug through the surface of the skin. The instrument includes an electrode containing the active agent (delivers charge) and an oppositely charged electrode (receives charge) which will be placed on the surface of the skin. The study design will consist of a screening visit to determine each individual's response to a previously established IV dose of NEO and GLY, followed by a dose titration study (two visits) of iontophoresed NEO and GLY. Study visits will be separated by no less than 2 days and no more than 14 days.

If this delivery method is shown to be effective, it may represent a way to vastly improve the clinical utility of this medication by allowing for needle-free self administration, and expanding the clinical indication to routine, at home bowel care.


Detailed Summary:

In this Phase I, proof of concept pilot study, we propose to study the safety and efficacy of transcutaneous neostigmine and glycopyrrolate facilitated by iontophoresis. The study design will consist of a screening visit to determine each individual's response to a previously established IV dose of NEO and GLY, followed by a dose titration study (two visits) of iontophoresed NEO and GLY. Study visits will be separated by no less than 2 days and no more than 14 days.

Screening Bowel Evacuation Study, Part 1: Visit 1 (30 Subjects with SCI):

A previously determined efficacious dose of IV neostigmine (0.03 mg/kg IV NEO) with glycopyrrolate (0.006 mg/kg GLY) will be administered during the first study visit to determine subject responsiveness to the known effective mode of administration. Irregardless of excess weight, the maximum dose of neostigmine and glycopyrrolate (NG) is limited to 10.0 mg and GLY to 2.0 mg. If the subject responds to the IV NEO, subsequent study visits to determine the effective dose of transcutaneous NEO and GLY will be performed. Subjects will be asked to arrive at the Spinal Cord Research Center at the James J. Peters Veteran Affairs Medical Center (JJP VAMC) (Room 7A-13) on the day of their scheduled study visits. Heart rate (continuous ecg), blood pressure, airway resistance (Impulse Oscillometry, IOS), signs and symptoms, and artificial bowel evacuation will be monitored throughout the study visit. Subjects will remain in this position until a bowel movement occurs, or for the next 60 minutes of the study. Subjects will be monitored for a minimum of 1.5 hours post drug, and until they reach ± 10% of their baseline heart rate (continuous 3 lead ECG) and airway caliber as measured by IOS.

Transcutaneous Bowel Evacuation Study, Part 2: Visits 2-3
Sponsor: James J. Peters Veterans Affairs Medical Center

Current Primary Outcome: Biological Responses to Study Drugs (quantified by the presence and strength of biological responses (changes in bowel sounds, heart rate and airway resistance and bowel movement occurrence) [ Time Frame: 6 months ]

We aim to determine the efficacy of transcutaneous (TC) neostigmine (NEO) with glycopyrrolate (GLY) delivered via iontophoresis in promoting bowel movement in persons with chronic SCI. This will be quantified by the presence and strength of biological responses (changes in bowel sounds, heart rate and airway resistance and bowel movement occurrence).


Original Primary Outcome: Same as current

Current Secondary Outcome: Safety of Study Medication (quantified through monitoring of side effects during study visits and through patient self report as measured by the Treatment Satisfaction Questionnaire) [ Time Frame: 6 Months ]

We aim to determine the safety and tolerability of TC NEO and GLY in persons with SCI when used to promote bowel movement. This will be quantified through monitoring of side effects during study visits and through patient self report as measured by the Treatment Satisfaction Questionnaire.


Original Secondary Outcome: Same as current

Information By: James J. Peters Veterans Affairs Medical Center

Dates:
Date Received: February 19, 2015
Date Started: February 2013
Date Completion:
Last Updated: March 6, 2017
Last Verified: March 2017