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

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ClinicalTrials.gov Identifier: NCT01370720
Recruitment Status : Unknown
Verified June 2012 by MARIA CRISTINA COMELLI, CM&D Pharma Limited.
Recruitment status was:  Recruiting
First Posted : June 10, 2011
Last Update Posted : June 19, 2012
Sponsor:
Information provided by (Responsible Party):
MARIA CRISTINA COMELLI, CM&D Pharma Limited

Tracking Information
First Submitted Date  ICMJE June 8, 2011
First Posted Date  ICMJE June 10, 2011
Last Update Posted Date June 19, 2012
Study Start Date  ICMJE February 2010
Estimated Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2011)
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:
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: June 9, 2011)
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 polidatin [ Time Frame: screening visit and after 12 weeks ]
Comparison between healthy volunteers and IBS patients (screening visit) on the following parameters:
  • number of mast cells (ICH)
  • mast cell activation, as per histamine and tryptase release in the surnatant of cultured biopsy samples
Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) on the following parameters:
  • number of mast cells (ICH)
  • mast cell activation, as per histamine and tryptase release in the surnatant of cultured biopsy samples
Change History Complete list of historical versions of study NCT01370720 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2011)
  • 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)
  • 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)
  • Safety assessment by no changes in laboratory parameters and vital signs [ Time Frame: 4, 8, 12 weeks after randomization ]
    • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2011)
  • 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 and PEA and 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 polidatin [ Time Frame: screening visit and after 12 weeks ]
    Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) in 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 ]
    • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of PEA and Polydatin on Intestinal Inflammation and Visceral Hyperalgesia in IBS Patients
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Irritable Bowel Syndrome
Intervention  ICMJE
  • Dietary Supplement: Recoclix
    tablets; 200 mg PEA+20 mg polydatin; 2 tablets/day; 12 weeks
  • Other: Placebo
    tablets, 2tablets/day, 12 weeks
Study Arms  ICMJE
  • Active Comparator: Recoclix (CM&D Pharma Limited)
    Recoclix: two tablets per day for 12 weeks
    Intervention: Dietary Supplement: Recoclix
  • Placebo Comparator: Placebo
    IBS patients
    Intervention: Other: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 9, 2011)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2013
Estimated Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01370720
Other Study ID Numbers  ICMJE CM&D Pharma Limited
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MARIA CRISTINA COMELLI, CM&D Pharma Limited
Study Sponsor  ICMJE MARIA CRISTINA COMELLI
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account CM&D Pharma Limited
Verification Date June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP