Safety and Efficacy Study of PEA and Polydatin on Intestinal Inflammation and Visceral Hyperalgesia in IBS Patients (CMD-IBS09(2))

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by CM&D Pharma Limited.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
MARIA CRISTINA COMELLI, CM&D Pharma Limited
ClinicalTrials.gov Identifier:
NCT01370720
First received: June 8, 2011
Last updated: June 16, 2012
Last verified: June 2012
  Purpose

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.

Condition Intervention Phase
Irritable Bowel Syndrome
Dietary Supplement: Recoclix
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by CM&D Pharma Limited:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    Comparison between healthy volunteers and IBS patients (screening visit) on the following parameters:

    • number of infiltrating mast cells (ICH)
    • mast cell activation, as per histamine and tryptase release in the surnatant of cultured colon biopsy samples

    Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) on the following parameters:

    • number of infiltrating mast cells (ICH)
    • mast cell activation, as per histamine and tryptase release in the surnatant of cultured colon biopsy samples


Secondary Outcome Measures:
  • Changes in biomarkers related to the endocannabinoid system [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]
    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)

  • 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 ] [ Designated as safety issue: No ]
    Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) of the number of other inflammatory cell subsets (ICH)

  • Safety assessment by no changes in laboratory parameters and vital signs [ Time Frame: 4, 8, 12 weeks after randomization ] [ Designated as safety issue: Yes ]
    • Laboratory test (blood cell count, AST, ALT, creatinine, gamma-GT, alkaline phosphatase, total bilirubin, glucose, N, Na, K, Ca)
    • Physical examination and vital signs (systolyc and diastolic blood pressure, heart rate, respiratory rate)


Estimated Enrollment: 60
Study Start Date: February 2010
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Recoclix (CM&D Pharma Limited)
Recoclix: two tablets per day for 12 weeks
Dietary Supplement: Recoclix
tablets; 200 mg PEA+20 mg polydatin; 2 tablets/day; 12 weeks
Placebo Comparator: Placebo
IBS patients
Other: Placebo
tablets, 2tablets/day, 12 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370720

Contacts
Contact: VINCENZO STANGHELLINI, MD +39 051 6364 ext 101 Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>
Contact: ROSANNA COGLIANDRO, MD +39 051 6364 ext 103 rosanna.cogliandro@aosp.bo.it

Locations
Italy
Dept Internal Medicine and Gastroenterology, Policlinico Sant'Orsola-Malpighi Recruiting
Bologna, Italy, I-40138
Contact: Vincenzo Stanghellini, MD    +39 051 6364101    Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>   
Contact: Rosanna Cogliandro, MD    +39 051 6364103    rosanna.cogliandro@aosp.bo.it   
Principal Investigator: Vincenzo Stanghellini, MD         
Sponsors and Collaborators
MARIA CRISTINA COMELLI
  More Information

No publications provided

Responsible Party: MARIA CRISTINA COMELLI, Head,R&D, CM&D Pharma Limited
ClinicalTrials.gov Identifier: NCT01370720     History of Changes
Other Study ID Numbers: CM&D Pharma Limited
Study First Received: June 8, 2011
Last Updated: June 16, 2012
Health Authority: Italy: Ethics Committee
Spain: Comité Ético de Investigación Clínica
France: Direction Générale de la Santé
Croatia: Ethics Committee

Keywords provided by CM&D Pharma Limited:
IBS
mast cell activation
low grade inflammation
visceral hyperalgesia

Additional relevant MeSH terms:
Inflammation
Irritable Bowel Syndrome
Hyperalgesia
Pathologic Processes
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on September 22, 2014