Inflammatory Bowel DiseasesNCT04794335
Visceral Afferents
An observational study of Inflammatory Bowel Diseases, run by University of Pittsburgh at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Inflammatory Bowel Diseases
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2023to 30 Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All subjects (>18), younger than 85, scheduled for abdominal surgery involving the removal of GI tissue for therapeutic purposes.
Who may be able to join
- This study's inclusion criteria are fairly straightforward: an adult (>18), younger than 85
- Scheduled for abdominal surgery involving the removal of GI tissue for therapeutic purposes
- Meets ASA 1-3 criteria.
Who cannot join
- Subject <18 years of age.
- Subject declines participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center (UPMC) Presbyterian
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Pharmacology of Visceral Afferents
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.
Read the detailed description
Visceral pain disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) remain a significant health problem both because of the large number of people who suffer from these disorders and because there are few, if any consistently effective therapeutic interventions. Thus, the goal of this project is to identify novel therapeutic approaches for the treatment of visceral pain.
The sensation of visceral pain is transmitted from visceral structures to the central nervous system via sensory neurons where the increase in pain associated with IBS and IBD is due, at least in part to increases in the excitability of these sensory neurons. Virtually all that scientists know about visceral sensory neurons was learned through the study of non-human species, in particular, rats and mice. A growing body of evidence suggests that many of the discoveries made in these species have failed to translate into more effective treatments because of species differences. To address this gap in knowledge, the investigators have proposed to study human tissue. Based on the investigator's preclinical data, they will start with a focus on GABA receptors, but will also explore other ionotropic receptors (for serotonin and ATP), as well as voltage gated ion channels. The investigators hypothesize that the dearth of effective treatments for visceral pain is due, at least in part, to species differences in the channels controlling the excitability of visceral sensory neurons. Electrophysiological techniques combined with pharmacological approaches will be used for a functional analysis of visceral afferents, and these endpoints will be complimented by biochemical, anatomical, and molecular biological analyses. Electrophysiological analysis of tissue will be performed on the day of surgery. Tissue will be processed and stored for biochemical, anatomical, and molecular biological analyses on the day of surgery, but analyzed once per month if it is possible to recover tissue from two patients per week.
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- pain, nociceptor, sensitization
- Medical subject headings
- Inflammatory Bowel Diseases, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Biochemical approaches such as western blot will be used to assess the presence and density of GABAA receptor signaling machinery (receptors, GABA transporters, etc), in human intestine. This analysis will be performed in tissue not used for pharmacological analysis.
Measured: Tissue for biochemical analysis will be flash frozen on day 1 of surgery.
Anatomical characterization of GABAA receptor signaling molecules in human intestine
Anatomical approaches such as immunohistochemistry will be used to assess the presence and density of GABAA receptor signaling machinery (receptors, GABA transporters, etc), in human intestine. This analysis will be performed in tissue not used for pharmacological analysis.
Measured: Tissue for anatomical analysis will be immersion fixed on day 1 of surgery.
Molecular biological characterization of GABAA receptor signaling molecules in human intestine
Molecular biological approaches such as semi-quantitative PCR will be used to assess the presence and density of GABAA receptor signaling machinery (receptors, GABA transporters, etc), in human intestine. This analysis will be performed in tissue not used for pharmacological analysis.
Measured: Tissue for molecular biological analysis will be flash frozen on day 1 of surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2021
- Study start1 Nov 2023 (estimated)
- Primary completion30 Apr 2025 (estimated)
- Study completion30 Apr 2025 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Gold, University of Pittsburgh
- Investigators
- Michael S Gold, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04794335
- Sponsor's protocol ID
- STUDY20070343
- Other IDs
- R01DK107966
- Status last verified
- Nov 2023
- First submitted
- 11 Feb 2021
- Last updated
- 3 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: All data generated from this study will be made publicly available through publications.
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacology of Visceral Afferents
- ClinicalTrials.gov ID
- NCT04794335
- Acronym / sponsor ID
- STUDY20070343
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- pain, nociceptor, sensitization
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- 30 Apr 2025 (estimated)
- Study completion
- 30 Apr 2025 (estimated)
- First posted
- 12 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Visceral pain disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) remain a significant health problem both because of the large number of people who suffer from these disorders and because there are few, if any consistently effective therapeutic interventions. Thus, the goal of this project is to identify novel therapeutic approaches for the treatment of visceral pain.
The sensation of visceral pain is transmitted from visceral structures to the central nervous system via sensory neurons where the increase in pain associated with IBS and IBD is due, at least in part to increases in the excitability of these sensory neurons. Virtually all that scientists know about visceral sensory neurons was learned through the study of non-human species, in particular, rats and mice. A growing body of evidence suggests that many of the discoveries made in these species have failed to translate into more effective treatments because of species differences. To address this gap in knowledge, the investigators have proposed to study human tissue. Based on the investigator's preclinical data, they will start with a focus on GABA receptors, but will also explore other ionotropic receptors (for serotonin and ATP), as well as voltage gated ion channels. The investigators hypothesize that the dearth of effective treatments for visceral pain is due, at least in part, to species differences in the channels controlling the excitability of visceral sensory neurons. Electrophysiological techniques combined with pharmacological approaches will be used for a functional analysis of visceral afferents, and these endpoints will be complimented by biochemical, anatomical, and molecular biological analyses. Electrophysiological analysis of tissue will be performed on the day of surgery. Tissue will be processed and stored for biochemical, anatomical, and molecular biological analyses on the day of surgery, but analyzed once per month if it is possible to recover tissue from two patients per week.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All subjects (>18), younger than 85, scheduled for abdominal surgery involving the removal of GI tissue for therapeutic purposes.
Key inclusion criteria (3 listed)
- This study's inclusion criteria are fairly straightforward: an adult (>18), younger than 85
- Scheduled for abdominal surgery involving the removal of GI tissue for therapeutic purposes
- Meets ASA 1-3 criteria.
Key exclusion criteria (2 listed)
- Subject <18 years of age.
- Subject declines participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Single unit activity in afferents innervating intestine specimen
Time frame: The presence of activity will be assessed immediately in each specimen recovered, day 1 of surgery.
The success of this ex vivo study will depend on the ability to record from afferent providing extrinsic innervation to the intestine.
The ability to identify receptive fields of visceral afferents in the intestine
Time frame: The presence of receptive fields will be assessed immediately in each specimen recovered, day 1 of surgery.
An electrical search strategy will be used to identify receptive fields in the ex vivo preparation
Pharmacological characterization of isolated visceral afferent
Time frame: Pharmacological analysis will be performed immediately on each specimen recovered day 1 of surgery.
The impact of GABAA agonists and/or agonist/antagonist combinations will be assessed in the ex vivo preparation
Changes in threshold of action potential generation in response to inflammatory mediators and/or GABAA agonists or agonist/antagonist combinations.
Time frame: Excitability will be analyzed immediately on each specimen recovered, day 1 of surgery.
The pharmacological characterization of isolated units will involve the assessment of changes in activity evoked with stretch of the intestine.
3 secondary outcomes
Biochemical characterization of GABAA receptor signaling molecules in human intestine
Time frame: Tissue for biochemical analysis will be flash frozen on day 1 of surgery.
Anatomical characterization of GABAA receptor signaling molecules in human intestine
Time frame: Tissue for anatomical analysis will be immersion fixed on day 1 of surgery.
Molecular biological characterization of GABAA receptor signaling molecules in human intestine
Time frame: Tissue for molecular biological analysis will be flash frozen on day 1 of surgery.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2023.
- Individual participant dataSharing planned: No. All data generated from this study will be made publicly available through publications.
Related trials for Inflammatory Bowel Diseases
Recruiting
A Randomized Crossover Trial of Bright Light Therapy in Crohn's Disease on Intestinal Barrier Homeostasis
Inflammatory Bowel Disease
Active, not recruitingPhase 2
Study Evaluating AZD7798 for Treatment in Crohn's Disease Patients With an Ileostomy
Crohn's Disease
RecruitingPhase 2
A Study of AC-101 Tablets in Patients With Ulcerative Colitis
Ulcerative Colitis (UC)
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael S Gold, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Bowel Diseases, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Single unit activity in afferents innervating intestine specimen (time frame: The presence of activity will be assessed immediately in each specimen recovered, day 1 of surgery.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2023.