Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05760404 |
| Other study ID # |
5309 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 19, 2022 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
February 2023 |
| Source |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
| Contact |
Roberto Persiani, MD |
| Phone |
+390630154974 |
| Email |
roberto.persiani[@]policlinicogemelli.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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. 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.
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.
