Visceral Afferents

NCT04794335 | Withdrawn

• 2 other identifiers: STUDY20070343R01DK107966
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The vast majority of what is known about the extrinsic innervation of the visceral was obtained through the study of preclinical models, primarily rats and mice. Given a growing list of important species differences, the investigators wish to determine the extent to which what scientists think they know about the control of visceral afferent excitability learned through the study of rodents holds true for humans. The investigators wish to establish an ex-vivo preparation using intestine surgically removed for the treatment of cancer, ischemia, etc, that would normally be disposed of as medical waste, to study the properties of the extrinsic innervation of the intestine. Tissue will be recovered in the OR, taken back to the lab, and evoked activity in the neurons innervating the intestine will be studied with extracellular recording techniques. Pharmacological approaches will be used to characterize the ion channels/receptors controlling the excitability of visceral afferents. After recording, tissue may be further analyzed with biochemical approaches such as western blot, PCR, and/or flow cytometry.

Conditions

Inflammatory Bowel Diseases

Keywords

pain; nociceptor; sensitization

Outcome Measures

Primary Outcomes (4)

• Single unit activity in afferents innervating intestine specimen

  The success of this ex vivo study will depend on the ability to record from afferent providing extrinsic innervation to the intestine.

  The presence of activity will be assessed immediately in each specimen recovered, day 1 of surgery.

• The ability to identify receptive fields of visceral afferents in the intestine

  An electrical search strategy will be used to identify receptive fields in the ex vivo preparation

  The presence of receptive fields will be assessed immediately in each specimen recovered, day 1 of surgery.

• Pharmacological characterization of isolated visceral afferent

  The impact of GABAA agonists and/or agonist/antagonist combinations will be assessed in the ex vivo preparation

  Pharmacological analysis will be performed immediately on each specimen recovered day 1 of surgery.

• Changes in threshold of action potential generation in response to inflammatory mediators and/or GABAA agonists or agonist/antagonist combinations.

  The pharmacological characterization of isolated units will involve the assessment of changes in activity evoked with stretch of the intestine.

  Excitability will be analyzed immediately on each specimen recovered, day 1 of surgery.

Secondary Outcomes (3)

• Biochemical characterization of GABAA receptor signaling molecules in human intestine

  Tissue for biochemical analysis will be flash frozen on day 1 of surgery.

• Anatomical characterization of GABAA receptor signaling molecules in human intestine

  Tissue for anatomical analysis will be immersion fixed on day 1 of surgery.

• Molecular biological characterization of GABAA receptor signaling molecules in human intestine

  Tissue for molecular biological analysis will be flash frozen on day 1 of surgery.

Study Arms (1)

Patients undergoing resection of intestine for therapeutic purposes

Tissue will be accepted from all eligible donors who consent to having their intestine removed for therapeutic purposes. This tissue would normally be disposed of as medical waste, used for research purposes. The tissue will be studied in the lab in a series of experiments involving GABA agonists and antagonists. Each GABA agonist and/or agonists/antagonist combination will be studied on intestine tissue randomly assigned to one of four groups defined by patient sex (m/f) and the application of inflammatory mediators (+/-). Thus, four groups are needed per GABA agonist and agonist/antagonist combination and seven agonist/antagonist combinations will be tested for a total of 28 experimental groups. But all of these groups will be generated from all patients recruited for the study.

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All subjects (\>18), younger than 85, scheduled for abdominal surgery involving the removal of GI tissue for therapeutic purposes.

You may qualify if:

• Scheduled for abdominal surgery involving the removal of GI tissue for therapeutic purposes
• Meets ASA 1-3 criteria.

You may not qualify if:

• Subject \<18 years of age.
• Subject declines participation.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Pittsburgh Medical Center (UPMC) Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

The only tissue recovered as part of this study is the intestine removed as part of a surgical procedure. Pieces of tissue to be analyzed for protein or mRNA will be stored at -80oC in a laboratory freezer. Tissue will be processed in batches. Any tissue not processed by the end of the 5 year study will be disposed of as medical waste.

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Pain

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael S Gold, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: March 12, 2021
• Study Start: November 1, 2023
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: November 3, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)