Irritable Bowel SyndromePhase 2CMD-IBS09(2)NCT01370720
Safety and Efficacy Study of PEA and Polydatin on Intestinal Inflammation and Visceral Hyperalgesia in IBS Patients
A Phase 2 study testing Recoclix in people with Irritable Bowel Syndrome, run by MARIA CRISTINA COMELLI at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- Recoclix
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2010to Jan 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
VINCENZO STANGHELLINI, MD contact
Italy1 site, 1 recruiting
- Recruiting
Dept Internal Medicine and Gastroenterology, Policlinico Sant'Orsola-Malpighi
Bologna, I-40138
Vincenzo Stanghellini, MD, +39 051 6364101, Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>
Rosanna Cogliandro, MD, +39 051 6364103, rosanna.cogliandro@aosp.bo.it
About this study
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.
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.
Read the 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
- Being tested
- Recoclix, Placebo
- Keywords
- IBS, mast cell activation, low grade inflammation, visceral hyperalgesia
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RecoclixDietary supplement
tablets; 200 mg PEA+20 mg polydatin; 2 tablets/day; 12 weeks
PlaceboOther
tablets, 2tablets/day, 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Recoclix (CM&D Pharma Limited) | Active comparator | Recoclix: two tablets per day for 12 weeks Receives: Dietary Supplement: Recoclix |
| Placebo | Placebo comparator | IBS patients Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: screening visit and after 12 weeks
Secondary outcomes (3)
Changes in biomarkers related to the endocannabinoid system
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)
Measured: 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
Comparison between active and placebo supplemented IBS patients (after 12 weeks from randomization) of the number of other inflammatory cell subsets (ICH)
Measured: screening visit and after 12 weeks
Safety assessment by no changes in laboratory parameters and vital signs
- 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)
Measured: 4, 8, 12 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2011 (estimated)
- Study startFeb 2010
- Primary completionDec 2012 (estimated)
- Study completionJan 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MARIA CRISTINA COMELLI
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor-investigator, MARIA CRISTINA COMELLI, CM&D Pharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01370720
- Sponsor's protocol ID
- CM&D Pharma Limited
- Acronym
- CMD-IBS09(2)
- Status last verified
- Jun 2012
- First submitted
- 8 Jun 2011
- Last updated
- 19 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 28164346
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01370720
- Acronym / sponsor ID
- CMD-IBS09(2) / CM&D Pharma Limited
- Conditions
- Irritable Bowel Syndrome
- Keywords
- IBS, mast cell activation, low grade inflammation, visceral hyperalgesia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- MARIA CRISTINA COMELLIIndustry (pharma, biotech, devices)
- Study start
- Feb 2010
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Jan 2013 (estimated)
- First posted
- 10 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Recoclix (CM&D Pharma Limited) | Active comparator | Dietary Supplement: RecoclixRecoclix: two tablets per day for 12 weeks |
| Placebo | Placebo comparator | Other: PlaceboIBS patients |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recoclixtablets; 200 mg PEA+20 mg polydatin; 2 tablets/day; 12 weeks | Dietary supplement | Recoclix (CM&D Pharma Limited) |
| Placebotablets, 2tablets/day, 12 weeks | Other | Placebo |
Primary outcome
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
3 secondary outcomes
Changes in biomarkers related to the endocannabinoid system
Time frame: 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
Safety assessment by no changes in laboratory parameters and vital signs
Time frame: 4, 8, 12 weeks after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2012.
- Derived from this study: PubMed 28164346Cremon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
VINCENZO STANGHELLINI, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Recoclix in people with Irritable Bowel Syndrome, run by MARIA CRISTINA COMELLI at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact VINCENZO STANGHELLINI, MD (+39 051 6364 ext. 101, Prof. Vincenzo Stanghellini <v.stanghellini@unibo.it>), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01370720, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2012.