Colorectal CancerCB1 - CONTRACTNCT05760404
Modulatory Effects of Active Drugs on the Endocannabinoid System on Spontaneous and Induced Contractility of the Colon
An observational study of Colorectal Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The endocannabinoid system plays important roles in the modulation of gastrointestinal motility and secretions. These effects are mainly mediated by the activation by the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) of CB1 receptors expressed on cholinergic neurons. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Surgery for colorectal cancer and in vitro study
- Type of treatment
- Surgery or procedure
- How many people
- 36 participants
- Where
- 1 siteItaly
- Study dates
- 19 Dec 2022to 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with colorectal cancer at any stage of the disease
Who may be able to join
- patients with colorectal cancer at any stage of the disease, undergoing upfront surgery or neo-adjuvant therapy for more than 6 weeks, to undergo surgery with resective intent at the UOC of General Surgery 1 of the Fondazione Policlinico Universitario A. Gemelli of Rome in the two years following the approval of the study by the Ethics Committee;
Who cannot join
- patients with diverticular stenosis, patients with stenosing colorectal cancer (defined as a tumor that cannot be passed through endoscopically, resulting in clinical and/or radiological symptoms of intestinal obstruction), urgent/emergency procedures, patients treated with corticosteroid therapy for immuno-rheumatic diseases, patients treated with radio-chemotherapy and undergone surgery for less than 6 weeks, surgically resected patients who present macroscopic lesions near the resection margin when opening the surgical piece, refusal of informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
The endocannabinoid system plays important roles in the modulation of gastrointestinal motility and secretions. These effects are mainly mediated by the activation by the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) of CB1 receptors expressed on cholinergic neurons. Cannabis sativa extracts also perform these activities, through the detection of CB1 receptors by the phytocannabinoids they contain, in particular delta9-tetrahydrocannabinol.
CB1 receptors are abundantly expressed at the synaptic terminals of excitatory motor neurons and cholinergic secretomotor neurons and their activation induces prejunctional inhibition of acetylcholine release. It is thought that the endocannabinoids AEA and 2-AG, by activating these receptors, may exert a physiological control on gastrointestinal contractility and secretions.
Read more
This research hypothesizes that drugs capable of inhibiting the biosynthetic and catabolic enzymes of endocannabinoids, of inhibiting the transmembrane transport of endocannabinoids or of allosterically modulating CB1 receptors induce important regulating effects of basal contractility and excitatory motor responses, induced by activation of neurons intramural cholinergics, of colonic circular smooth muscle.
The effects of drugs acting on CB receptors, endocannabinoid biosynthetic and catabolic enzymes and endocannabinoid membrane transporters on basal contractility or induced by neuronal activation of colonic preparations in vitro will be evaluated.
The study will enroll patients affected by colorectal cancer to undergo elective resective surgery at any stage, undergoing upfront surgery or after neo-adjuvant therapy with a therapeutic interval greater than 6 weeks. In the selected patients (see inclusion/exclusion criteria), a fresh sample of about 2.5 cm of healthy colon (healthy resection margin) will be taken, which will be taken in the operating room and sent to the laboratory for in vitro study.
Expected results: The study is expected to provide new evidence regarding the induction of pharmacological effects by allosteric receptor modulators of CB1 receptors, inhibitors of endocannabinoid biosynthetic and catabolic enzymes, and inhibitors of cannabinoid transporters in the human colon, which may open interesting perspectives regarding the development of new therapeutic strategies for the treatment of constipation, diarrhea and irritable bowel syndrome.
Read the detailed description
The present research is aimed at defining the roles of the different components of the endocannabinoid system in the regulation of the basal contractile activity and of the excitatory motor responses induced by neuronal activation in the human colon.
Therefore, the motor effects of drugs acting on the various components of this system will be evaluated, ie receptors, biosynthetic and catabolic enzymes and membrane transporters, in colonic preparations, in conditions of basal muscle tone and on muscle contractions induced by neuronal activation.
If the modulation of one or more components of the endocannabinoid system proves to be important in the regulation of colonic contractility and probably useful for therapeutic purposes, drugs active on them could represent new treatments for constipation, diarrhea or some forms of irritable bowel syndrome, very common in the gastrointestinal tract.
Particular interest will be focused on the effects of allosteric modulators of CB1 receptors, inhibitors of biosynthetic and catabolic enzymes of endocannabinoids and inhibitors of membrane transporters of endocannabinoids.
This is an exploratory study, in which pre-specified hypotheses on pre-specified sample sizes will not be tested. Therefore, the data will be subjected only to descriptive statistics, without conducting any tests of statistical significance on them. Consequently, no primary or secondary endpoints are foreseen.
- Conditions
- Colorectal Cancer
- Being tested
- Surgery for colorectal cancer, in vitro study
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgery for colorectal cancerProcedure or surgery
Patients undergoing upfront surgery or surgery after neoadjuvant therapy for colorectal cancer with curative intention
in vitro studyOther
on tissues from colorectal resections
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the motor effects of drugs that act on the various components of this system
Evaluate the motor effects of drugs that act on the various components of this system, like receptors, biosynthetic and catabolic enzymes and membrane transporters, in colic tissues, in conditions of basal muscle tone and on muscle contractions induced by neuronal activation.
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2023
- Study start19 Dec 2022
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, PERSIANI ROBERTO, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05760404
- Sponsor's protocol ID
- 5309
- Acronym
- CB1 - CONTRACT
- Status last verified
- Sep 2025
- First submitted
- 27 Feb 2023
- Last updated
- 8 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulatory Effects of Active Drugs on the Endocannabinoid System on Spontaneous and Induced Contractility of the Colon
- ClinicalTrials.gov ID
- NCT05760404
- Acronym / sponsor ID
- CB1 - CONTRACT / 5309
- Conditions
- Colorectal Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 19 Dec 2022 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 8 Mar 2023 (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 endocannabinoid system plays important roles in the modulation of gastrointestinal motility and secretions. These effects are mainly mediated by the activation by the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) of CB1 receptors expressed on cholinergic neurons. Cannabis sativa extracts also perform these activities, through the detection of CB1 receptors by the phytocannabinoids they contain, in particular delta9-tetrahydrocannabinol.
CB1 receptors are abundantly expressed at the synaptic terminals of excitatory motor neurons and cholinergic secretomotor neurons and their activation induces prejunctional inhibition of acetylcholine release. It is thought that the endocannabinoids AEA and 2-AG, by activating these receptors, may exert a physiological control on gastrointestinal contractility and secretions.
This research hypothesizes that drugs capable of inhibiting the biosynthetic and catabolic enzymes of endocannabinoids, of inhibiting the transmembrane transport of endocannabinoids or of allosterically modulating CB1 receptors induce important regulating effects of basal contractility and excitatory motor responses, induced by activation of neurons intramural cholinergics, of colonic circular smooth muscle.
The effects of drugs acting on CB receptors, endocannabinoid biosynthetic and catabolic enzymes and endocannabinoid membrane transporters on basal contractility or induced by neuronal activation of colonic preparations in vitro will be evaluated.
The study will enroll patients affected by colorectal cancer to undergo elective resective surgery at any stage, undergoing upfront surgery or after neo-adjuvant therapy with a therapeutic interval greater than 6 weeks. In the selected patients (see inclusion/exclusion criteria), a fresh sample of about 2.5 cm of healthy colon (healthy resection margin) will be taken, which will be taken in the operating room and sent to the laboratory for in vitro study.
Expected results: The study is expected to provide new evidence regarding the induction of pharmacological effects by allosteric receptor modulators of CB1 receptors, inhibitors of endocannabinoid biosynthetic and catabolic enzymes, and inhibitors of cannabinoid transporters in the human colon, which may open interesting perspectives regarding the development of new therapeutic strategies for the treatment of constipation, diarrhea and irritable bowel syndrome.
Detailed description
The present research is aimed at defining the roles of the different components of the endocannabinoid system in the regulation of the basal contractile activity and of the excitatory motor responses induced by neuronal activation in the human colon.
Therefore, the motor effects of drugs acting on the various components of this system will be evaluated, ie receptors, biosynthetic and catabolic enzymes and membrane transporters, in colonic preparations, in conditions of basal muscle tone and on muscle contractions induced by neuronal activation.
If the modulation of one or more components of the endocannabinoid system proves to be important in the regulation of colonic contractility and probably useful for therapeutic purposes, drugs active on them could represent new treatments for constipation, diarrhea or some forms of irritable bowel syndrome, very common in the gastrointestinal tract.
Particular interest will be focused on the effects of allosteric modulators of CB1 receptors, inhibitors of biosynthetic and catabolic enzymes of endocannabinoids and inhibitors of membrane transporters of endocannabinoids.
This is an exploratory study, in which pre-specified hypotheses on pre-specified sample sizes will not be tested. Therefore, the data will be subjected only to descriptive statistics, without conducting any tests of statistical significance on them. Consequently, no primary or secondary endpoints are foreseen.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with colorectal cancer at any stage of the disease
Key inclusion criteria (1 listed)
- patients with colorectal cancer at any stage of the disease, undergoing upfront surgery or neo-adjuvant therapy for more than 6 weeks, to undergo surgery with resective intent at the UOC of General Surgery 1 of the Fondazione Policlinico Universitario A. Gemelli of Rome in the two years following the approval of the study by the Ethics Committee;
Key exclusion criteria (1 listed)
- patients with diverticular stenosis, patients with stenosing colorectal cancer (defined as a tumor that cannot be passed through endoscopically, resulting in clinical and/or radiological symptoms of intestinal obstruction), urgent/emergency procedures, patients treated with corticosteroid therapy for immuno-rheumatic diseases, patients treated with radio-chemotherapy and undergone surgery for less than 6 weeks, surgically resected patients who present macroscopic lesions near the resection margin when opening the surgical piece, refusal of informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surgery for colorectal cancerPatients undergoing upfront surgery or surgery after neoadjuvant therapy for colorectal cancer with curative intention | Procedure or surgery | – |
| in vitro studyon tissues from colorectal resections | Other | – |
Primary outcome
Evaluate the motor effects of drugs that act on the various components of this system
Time frame: 30 months
Evaluate the motor effects of drugs that act on the various components of this system, like receptors, biosynthetic and catabolic enzymes and membrane transporters, in colic tissues, in conditions of basal muscle tone and on muscle contractions induced by neuronal activation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2025.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Colorectal Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 8 Sep 2025. 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 Italy. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluate the motor effects of drugs that act on the various components of this system (time frame: 30 months). 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 8 Sep 2025.