Intrarectal Mechanoreceptor Sensitization to Induce Defecation After Spinal Injury
Abstract
This project aims to address an area of great unmet need by restoring voluntary control over the time and place of bowel emptying to people with spinal cord injury (SCI) using a prescription drug. Most SCI individuals must employ manual stimulation of the rectum to initiate defecation, which can be undignified, burdensome, and time consuming. Regular and efficient emptying of the bowel is necessary to prevent complications of constipation, fecal impaction, and incontinence. The unpredictable timing and incomplete bowel emptying produced by reflex bowel movements in people with SCI is socially stigmatizing and the ensuing medical, financial, social, and psychological sequelae impair quality of life. Improved bowel control is ranked among the highest priorities of people with SCI. Most people with SCI frequently supplement their bowel programs with oral laxatives, suppositories, or enemas. The timing of their effects is unpredictable, and they may themselves cause incontinence since diarrhea is a common side-effect. According to the directions for use provided on their packaging, no laxative should be used for more than 7 consecutive days. This precaution reflects the risk of gastrointestinal damage, colorectal cancer, and loss of intestinal muscle tone reported after chronic use of these products. Despite this warning, many people with SCI are forced to use laxatives every day because no alternatives are available. We propose to address this unmet medical need by replacing time-consuming bowel programs with a fast- acting, short-lasting prescription drug to induce defecation on demand. The drug will induce rapid and efficient bowel emptying at a time and place chosen by the person with SCI. Any excess drug will be rapidly eliminated from the body with the feces, so that its effects will be short-lasting and predictable. Our objective is to enable people with SCI to complete a daily bowel program in around 15 minutes and then be free to go about their daily tasks without worrying about fecal incontinence, and in doing so will improve the quality of life for SCI individuals. Dignify has completed experiments with both spinally injured and naive rats that confirm the ability of our drug to induced rapid onset, short-lasting defecation when it is applied directly into the rectum. We are seeking funding from Spinal Cord Injury Research Program to conduct the necessary preclinical work to enable us to examine the effects of our drug in healthy able-bodied volunteers and people with SCI. This involves identifying the most suitable formulation of our drug that produces rapid defecation with minimal absorption into the bloodstream. In accordance with regulatory requirements, the safety of our optimized formulation will be tested in preclinical studies to ensure that it does not cause damage to the lining of the rectum after repeated daily administration. On completion of these studies, Dignify will prepare and submit an Investigational New Drug application to the Food and Drug Administration for initiation of clinical trials. It is hoped that the initiation of the phase 1 clinical trials could commence within 1 year of completion of the proposed studies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310403
Entities
People
- Lesley Marson
Organizations
- Inotiv
- United States Army