- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01370720
Safety and Efficacy Study of PEA and Polydatin on Intestinal Inflammation and Visceral Hyperalgesia in IBS Patients (CMD-IBS09(2))
Effect of the Oral Administration in IBS Patients of the Association of 200 mg Micronised Palmitoylethanolamide (PEA) and 20 mg Polydatin, on Parameters of Intestinal Inflammation and Visceral Hyperalgesia.
Despite the pathophysiology of IBS remains largely unsettled, several mechanisms have been proposed to explain symptom generation. These include psychosocial factors, altered gastrointestinal motor function and altered perception of visceral stimuli because of chronic low-grade inflammation and increased nociceptive mediator release by inflammatory cells, particularly mast cells.
The aim of this pilot study is to provide evidence of:
- intestinal mast cell (MC) infiltration and activation in IBS patients;
- down-modulation of MC activation by the oral administration of the association of palmitoylethanolamide (PEA) and polydatin in IBS patients.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The number of inflammatory cells in the gut wall of IBS patients is increased in comparison to asymptomatic controls. A significant increase in the number of both mast cells and T-lymphocytes in the mucosa of IBS patients have been reported. Electron microscopic studies demonstrated that mast cells were more frequently degranulated in IBS, suggesting their increased state of activation. Accordingly, an increased mucosal release of preformed mediators, such as histamine and tryptase, as well as de novo synthesis and secretion of arachidonic acid end products (e.g. prostaglandin E2) have been demonstrated. These mediators are known to target sensory nerve pathways, including those innervating the gastrointestinal tract, leading to visceral hyperalgesia.
Electron microscopic studies showed that the mean distance between inflammatory cells and enteric nerves is significantly reduced in IBS patients, thus providing a conceptual basis for a putative pathogenetic role of low-grade inflammation on sensory-motor dysfunction in IBS. Activated mast cells in close proximity to mucosal colonic innervation correlated with the frequency and severity of abdominal pain. Evidence that mast cell mediators of IBS patients, but not controls, evoked activation of nociceptive sensory afferent neurons are available, thus providing a possible mechanism through which mast cells can evoke pain in IBS patients. Similar results has been recently reported following the administration into the rat colon of supernatants collected from human IBS colonic biopsy samples in culture. This nociceptive effect on murine sensory neurons was inhibited by serine protease inhibitors and a Protease Activating Receptor-2 antagonist.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: VINCENZO STANGHELLINI, MD
- Phone Number: 101 +39 051 6364
- Email: Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>
Study Contact Backup
- Name: ROSANNA COGLIANDRO, MD
- Phone Number: 103 +39 051 6364
- Email: rosanna.cogliandro@aosp.bo.it
Study Locations
-
-
-
Bologna, Italy, I-40138
- Recruiting
- Dept Internal Medicine and Gastroenterology, Policlinico Sant'Orsola-Malpighi
-
Contact:
- Vincenzo Stanghellini, MD
- Phone Number: +39 051 6364101
- Email: Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>
-
Contact:
- Rosanna Cogliandro, MD
- Phone Number: +39 051 6364103
- Email: rosanna.cogliandro@aosp.bo.it
-
Principal Investigator:
- Vincenzo Stanghellini, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- IBS patients (both males and females) with positive diagnosis based on Rome III criteria (all IBS subtypes will be included)
- Age in the range 18-70 years
- Subjects capable of conforming to the study protocol
- Subjects who have given their free and informed consent
Exclusion Criteria:
- Any relevant organic, systemic or metabolic disease, such as celiac disease, IDDM (Insulin-Dependant Diabetes Mellitus), Insulin-Independent Diabetes Mellitus, metabolic syndrome, pelvic organ prolapse, and urinary incontinence.
- Subjects with ascertained intestinal organic diseases (ulcerative colitis, Crohn's disease, microscopic colitis, infectious colitis, ischemic colitis, complicated diverticular disease).
- Subjects with untreated food intolerance, i.e. remaining symptomatic despite the withdrawal of the suspected food
- Previous major abdominal surgeries
- Females of childbearing potential, in the absence of effective contraceptive methods
- Subjects who become unable to conform to protocol
- Subjects who are continuously taking contact laxatives
- Subjects who have been continuously administered glucocorticoids, anti-histaminergic and mast cell stabilizer drugs within the previous 30 days
- Subjects who have been continuously administered trimebutine within the previous 30 days
- Treatment with any investigational drug within the previous 30 days
- Recent history or suspicion of alcohol abuse or drug addiction
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Recoclix (CM&D Pharma Limited)
Recoclix: two tablets per day for 12 weeks
|
tablets; 200 mg PEA+20 mg polydatin; 2 tablets/day; 12 weeks
|
Placebo Comparator: Placebo
IBS patients
|
tablets, 2tablets/day, 12 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes from screening visit of mast cell infiltration and activation in biopsy samples of colon mucosa from IBS patients, following 12 weeks of dietary supplementation with palmitoylethanolamide (PEA) and polydatin
Time Frame: screening visit and after 12 weeks
|
Comparison between healthy volunteers and IBS patients (screening visit) on the following parameters:
Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) on the following parameters:
|
screening visit and after 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in biomarkers related to the endocannabinoid system
Time Frame: 12 weeks after randomization
|
Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) on the level of anandamide, 2-AG, PEA, CB1, CB2, FAAH (LC-APCI-MS; immunoblotting)
|
12 weeks after randomization
|
Changes from screening visit of other inflammatory cell subsets in biopsy samples of colon mucosa from IBS patients, following 12 weeks of dietary supplementation with palmitoylethanolamide (PEA) and polydatin
Time Frame: screening visit and after 12 weeks
|
Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) of the number of other inflammatory cell subsets (ICH)
|
screening visit and after 12 weeks
|
Safety assessment by no changes in laboratory parameters and vital signs
Time Frame: 4, 8, 12 weeks after randomization
|
|
4, 8, 12 weeks after randomization
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CM&D Pharma Limited
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Irritable Bowel Syndrome
-
ProgenaBiomeRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome Characterized by Constipation | Irritable Bowel Syndrome Mixed | Irritable Bowel Syndrome Without Diarrhea | Irritable Bowel | Irritable Bowel Syndrome Aggravated and other conditionsUnited States
-
ClasadoCR2O B.V.RecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome - Constipation | Irritable Bowel Syndrome - Diarrhoea | Irritable Bowel Syndrome - MixedBelgium, Netherlands, United Kingdom
-
Istanbul Medipol University HospitalTepecik Training and Research Hospital; Bozyaka Training and Research Hospital and other collaboratorsRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedTurkey
-
Federal Stare Budgetary Scientific Institution,...I.M. Sechenov First Moscow State Medical University; RML INVEST, Torkhovsky...CompletedIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedRussian Federation
-
University of California, Los AngelesCompletedIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Mixed Bowel HabitsUnited States
-
University of ViennaCompleted
-
Thomayer University HospitalCharles University, Czech RepublicActive, not recruitingIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome MixedCzechia
-
Shahid Beheshti University of Medical SciencesCompletedIrritable Bowel DiseaseIran, Islamic Republic of
-
Universidad Autonoma de ChihuahuaNot yet recruitingIrritable Bowel Syndrome | Constipation-predominant Irritable Bowel Syndrome | Diarrhea- Irritable Bowel Syndrome
-
Vasily IsakovRussian Science Foundation; Azbuka vkusa; Federal Research Centre of Nutrition...CompletedIrritable Bowel Syndrome With Constipation | Constipation-predominant Irritable Bowel SyndromeRussian Federation