Safety and Efficacy Study of PEA and Polydatin on Intestinal Inflammation and Visceral Hyperalgesia in IBS Patients

NCT ID: NCT01370720

Last Updated: 2012-06-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2013-01-31

Brief Summary

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:

1. intestinal mast cell (MC) infiltration and activation in IBS patients;

2. down-modulation of MC activation by the oral administration of the association of palmitoylethanolamide (PEA) and polydatin in IBS patients.

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.

Conditions

Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Recoclix (CM&D Pharma Limited)

Recoclix: two tablets per day for 12 weeks

Group Type: ACTIVE_COMPARATOR

Recoclix

Intervention Type: DIETARY_SUPPLEMENT

tablets; 200 mg PEA+20 mg polydatin; 2 tablets/day; 12 weeks

Placebo

IBS patients

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

tablets, 2tablets/day, 12 weeks

Interventions

Recoclix

tablets; 200 mg PEA+20 mg polydatin; 2 tablets/day; 12 weeks

Intervention Type: DIETARY_SUPPLEMENT

Placebo

tablets, 2tablets/day, 12 weeks

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

MARIA CRISTINA COMELLI

INDUSTRY

Sponsor Role: lead

Responsible Party

MARIA CRISTINA COMELLI

Head,R&D

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Dept Internal Medicine and Gastroenterology, Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

VINCENZO STANGHELLINI, MD

Role: CONTACT

Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>

+39 051 6364 ext. 101

ROSANNA COGLIANDRO, MD

Role: CONTACT

rosanna.cogliandro@aosp.bo.it

+39 051 6364 ext. 103

Facility Contacts

Vincenzo Stanghellini, MD

Role: primary

Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>

+39 051 6364101

Rosanna Cogliandro, MD

Role: backup

rosanna.cogliandro@aosp.bo.it

+39 051 6364103

References

Cremon C, Stanghellini V, Barbaro MR, Cogliandro RF, Bellacosa L, Santos J, Vicario M, Pigrau M, Alonso Cotoner C, Lobo B, Azpiroz F, Bruley des Varannes S, Neunlist M, DeFilippis D, Iuvone T, Petrosino S, Di Marzo V, Barbara G. Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome. Aliment Pharmacol Ther. 2017 Apr;45(7):909-922. doi: 10.1111/apt.13958. Epub 2017 Feb 6.

Reference Type: DERIVED

PMID: 28164346 (View on PubMed)

Other Identifiers

CM&D Pharma Limited

Identifier Type: -

Identifier Source: org_study_id