Abstract
Study design
Phase I Clinical Trial.
Objectives
In this proof-of-principle study, the effectiveness and safety of transdermal administration of neostigmine/glycopyrrolate to elicit a bowel movement was compared to intravenous administration in patients with spinal cord injury.
Setting
James J. Peters Veterans Affairs Medical Center (Bronx, NY).
Methods
Individuals were screened for responsiveness (Physical Response) to intravenous neostigmine (0.03 mg/kg)/glycopyrrolate (0.006 mg/kg). Intravenous neostigmine/glycopyrrolate responders (Therapeutic Response) were administered low-dose transdermal neostigmine/glycopyrrolate [(0.05 mg/kg)/(0.01 mg/kg)] by iontophoresis. Non-responders to low-dose transdermal neostigmine/glycopyrrolate were administered high-dose transdermal neostigmine/glycopyrrolate [(0.07 mg/kg)/(0.014 mg/kg)] by iontophoresis. Bowel movement, bowel evacuation time, and cholinergic side effects were recorded. Visits were separated by 2 to 14 days.
Results
Eighteen of 25 individuals (72.0%) had a bowel movement (20 ± 22 min) after intravenous neostigmine/glycopyrrolate. Of these 18 individuals, 5 individuals experienced a bowel movement with low-dose transdermal neostigmine/glycopyrrolate. Another five individuals had a bowel movement after high-dose transdermal neostigmine/glycopyrrolate administration. Fewer side effects were observed in individuals who received neostigmine/glycopyrrolate transdermally compared to those who were administered intravenous neostigmine/glycopyrrolate.
Conclusions
Transdermal administration of neostigmine/glycopyrrolate by iontophoresis appears to be a practical, safe, and effective approach to induce bowel evacuation in individuals with spinal cord injury.
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Acknowledgments
We thank Ms. Oriana Tascione, research coordinator in the NCMSCI, who assisted in subject recruitment and protocol implementation; Dr. Ravi Vinnakota, who assisted in the oversight of neostigmine and glycopyrrolate administration; Dr. Marinella Galea, a staff physician in Spinal Cord Services; and Dr. Sandeep Kahal who have assisted in subject recruitment.
Author Contributions
M.A.K. Chief of Gastroenterology and Invasive Gastroenterology, is the guarantor of this submission. M.A.K. was primarily responsible for protocol design and implementation. B.L.L. research coordinator in the National Center for the Medical Consequences of Spinal Cord Injury (NCMCSCI), was responsible for subject recruitment, protocol implementation, and assisted with the preparation of this manuscript. M.R. a Veterans Affairs Career Development Awardee, oversaw administration of neostigmine and glycopyrrolate. T.C. research coordinator in the NCMCSCI, assisted with the preparation of this manuscript, statistical analysis of the data, and subject recruitment. G.S. performed statistical analysis of the data. K.S. assisted in subject recruitment and protocol implementation. J.H. research coordinator in the NCMCSCI, assisted in subject recruitment and protocol implementation. A.M.S. the Associate Director of NCMCSCI, assisted with the protocol design, and along with A.S. worked on the statistical analysis and the writing of this manuscript. W.A.B. the Director of NCMCSC, was responsible for the conceptualization of this project with M.A.K. and assisted in the preparation of the protocol and the manuscript. All authors listed on this study have read and approved the final version being submitted for consideration of publication.
Funding
This research was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (#B9212-C) and the James J. Peters VA Medical Center.
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M.A.K. and W.A.B. are co-inventors of this bowel intervention and have processed a patent (patent number: 7.635,709) and a provisional patent (62/2984,874) for the administration of neostigmine and glycopyrrolate via iontophoresis through the Office of Technology Transfer Program, Department of Veterans Affairs. M.A.K. reports grants from Department of Veteran Affairs Rehabilitation Research and Development Service, during the conduct of the study; In addition, M.A.K. has a patent 7.635,709 licensed to Technology Transfer Program of the Department of Veterans Affairs. W.A.B. reports grants from Department of Veteran Affairs Rehabilitation Research and Development Service, during the conduct of the study; In addition, W.A.B. has a patent 7.635,709 licensed to Technology Transfer Program of the Department of Veterans Affairs.
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Korsten, M.A., Lyons, B.L., Radulovic, M. et al. Delivery of neostigmine and glycopyrrolate by iontophoresis: a nonrandomized study in individuals with spinal cord injury. Spinal Cord 56, 212–217 (2018). https://doi.org/10.1038/s41393-017-0018-2
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DOI: https://doi.org/10.1038/s41393-017-0018-2
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