Clinical trial NCT02573844: Pain Relief In Irritable Bowel Syndrome
Official title: Efficacy of Proklama on Patients' Symptoms With Irritable Bowel Syndrome: Clinical Trial, Double- Blind, Crossover, Controlled Study vs. Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritable Bowel Syndrome
Keywords: irritable bowel syndrome
abdominal pain
rome III criteria
abdominal distension
consistency of stools
stool frequency
meteorism
flatulence
abdominal discomfort
proklama
probiotics
alga klamath
aphanizomenon flos-aquae
prebiotics
colitis ulcerosa
Lead sponsor: Geophyt S.r.l.s.
Sponsor class: INDUSTRY
First posted: 2015-10-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Proklama is effective in significative reduction of pain, other symptoms IBS's related, and improves quality of life concerning IBS disease.

Detailed description: This is a phase IV, double- blind, randomized, placebo controlled, monocentric study.

Males and women over 18 y.o. with Irritable bowel syndrome (IBS) diagnosed applying Rome III criteria will be enrolled consecutively.

The study consist of 4 periods:

* A screening's period of 2 weeks starting from visit 1, useful to screen potentially eligible patients performing diagnostic investigations necessary to confirm diagnosis.
* A run- in's period, starting from visit 2 and lasting 2 weeks will represent a baseline without specific treatments in order to characterize the severity of symptomatology and evaluate patients' compliance relative to daily diaries
* A 2 weeks- treatment's period ( active/ placebo) starting from visit 3. The 1st day of the period of treatment, eligible patients will be randomized following a 1:1 ratio to receive Proklama ( 1 sachet/ day) or placebo. Treatments will be administered daily during the whole 2 weeks- treatment's period.
* A wash out's period lasting 2 weeks starting from visit 4, to be performed the day after the end of the 2 weeks- treatment's period.
* A 2 weeks- treatment's period ( placebo/ active) starting from visit 5, to be performed the last day of wash out's period. During this visit patients will receive the second treatment, following a crossover design.

Eligibility criteria: Inclusion Criteria:

1. patients over 18 y.o.
2. clinical diagnosis of IBS following Rome III symptom- based criteria:

   1. abdominal pain or discomfort recurring for at least 3 days a month in the previous 3 months, associated with 2 of the following characteristics at least: improved with evacuation; onset associated with variation of stool frequency; onset associated with changes in stool consistency
   2. onset of symptomatology at least 6 months preceding diagnosis
   3. additional criterion: mean severity of abdominal pain higher than 3 in the 11-points NRS
3. For patients over 50 y.o. or with positive familiarity for colorectal cancer: normal colonoscopy performed within 5 years from the beginning of the screening's period and after symptomatology's onset
4. For patients over 65 y.o. : absence of ischemic / microscopic colitis, or other organic gastrointestinal disorders, as highlighted through colonoscopy with biopsy performed within 6 months from the beginning of the screening's period
5. For fertile and sexually active women: use of effective contraception with failure rate of less than 1% for one year during the trial period and 30 days after its end.

   Oral contraceptive are admitted as long as formulation didn't undergo changes during the 6 months preceeding the trial.
6. Physical examination is negative during the period of screening
7. Absence of significant alterations in 12- lead ECG during the period of screening.
8. Normal haematochemical parameters during the period of screening
9. Compliant patients towards procedures provided for the study, especially the use of daily diary
10. Patients with mental integrity, able to express an informed before any procedure related to protocol, compliant toward clinical examinations provided for the protocol.
11. Patients willing to avoid loperamide and laxatives use during the 3 days preceding run in and during the whole run in's period ( to be verified before randomization)
12. Patients that during both the 2 run in's weeks reported an average daily intensity of abdominal pain for every week \>3 on 0-10 (NRS)

Exclusion Criteria:

1. Male gender
2. Patient has a diagnosis of IBS with a subtype of constipation, mixed IBS, or unsubtyped IBS according to the Rome III criteria
3. Patient has had surgery that meets any of the following criteria:

   a) colonic or major abdominal surgery, i.e. bariatric surgery and stomach, small/ large bowel or large vessel abdominal surgery ( except appendicectomy, hysterectomy, cholecystectomy, caesarean section, or laparoscopic surgery).
4. Patient has any elective major surgery planned or expected at any time during the study.
5. Patient has a history of inflammation bowel diseases, complicated diverticulosis ( i.e. diverticulitis), ischaemic colitis, microscopic colitis.
6. Patient has a history of organic abnormalities of the GI tract, intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, adhesions or impaired intestinal circulation ( e.g., aortoiliac disease).
7. Patient has a history of pancreatitis of any etiology, cholecystitis or of symptomatic gallbladder stone disease in the previous 6 months.
8. Patient has an active biliary duct disease of a history of Sphincter of Oddi dysfunction.
9. Patient has a history of gluten enteropathy.
10. Patient has a history of lactose intolerance as assessed by response to diet.
11. Patient has a current or previous diagnosis of neoplasia ( except non-GI) neoplasia in complete remission \< or = 5 years, squamous and basal cell carcinomas and cervical carcinoma in situ).
12. Patient has a history of ectopic endometriosis.
13. Patient has a history of positive tests for ova or parasites, or clostridium difficile toxin or occult blood in the stool in the previous 6 months.
14. Patient has a history of human immunodeficiency virus infection.
15. Patient has a history of a cardiovascular event, including stroke, myocardial infarction, congestive heart failure ( NYHA class \> 2), or transient ischemic attack in the previous 6 months.
16. Patient has uncontrolled hypertension, defined as systolic blood pressure \<180 mmHg or a diastolic blood pressure \< 100 mmHg.
17. Patient has insulin- dependent diabetes mellitus.
18. Patient has a major pshychiatric or neurological disorders.
19. Patient has an unstable medical condition which may compromise the efficacy and safety assessments as required in the study and/or require change in concomitant medication.
20. Patient has a history of abnormal thyroid function. Patient is candidate for the study if thyroid hormone replacement therapy is stable from at least 2 months.
21. Patient has evidence of clinically hepatic disease as defined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times rthe upper limit of normal or total bilirubin \>3 mg/dl (\>51.3 mmoL/L), with the exception of Gilbert's syndrome or albumin \< 2.8 g/dL during the Screening period.
22. Patient has a sever renal insufficiency ( Glomerular Filtration Rate \[GFR\] \<30 mL/min/ 1.73 m\^2 calculated by the Cockcroft. Gault formula adjusted for the body surface area \[BSA\]) during the Screening period
23. Patient has evidence of anemia as confirmed by hemoglobin \< 9 g/dL during the Screening period.
24. Relevant changes in dietary habits, lifestyle or exercise regimen should be maintained for the duration of the study.
25. Use of prohibited concurrent medication within the previous month, namely:

    * Antibiotics ( 4 months in the case of rifaximin);
    * 5- HT3 antagonists alosetron.
26. Use of prohibited concurrent medication in the previous 7 days namely:

    * Antimuscarinic drugs;
    * Drug enhancing GI motility such as prokinetic agents and other stimulants of GI contractility drugs, laxatives, or anti- diarrhoeal agents ( except for loperamide, please refer to inclusion criterion No.12);
    * Analgesic drugs ( opioids or non- steroidal anti- inflammatory drugs). NOTE: short term use of paracetamol is allowed for max 2 consecutive days;
    * Fibre products and herbal preparations;
    * Antidepressants. NOTE: the use of a single antidepressant is only allowed when the drug type and its dose regimen have not been changed in the previous 6 months;
    * Benzodiazepines. NOTE: the use of a single benzodiazepine is only allowed when it is administered as sleep- inducer and the drug type and its dose regimen have not been changed in the previous 6 months.
27. Pregnancy or breastfeeding.
28. Hypersensitivity to the drug excipients.
29. Patient is not able to understand or collaborate throughout the study.
30. Patient is unable to swallow solid, oral dosage forms whole with the aid of liquid ( patients may not chew, divide, dissolve, or crush the study drug).
31. Partecipation in other clinical studies in the previous 4 weeks or the patient is currently enrolled in a clinical study with another investigational drug.
32. Patient has any condition that, in the opinion of the Investigator, would compromise the well- being of the patient or the requirements of the study.

Primary outcomes:
measure: Recorded pain in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
Secondary outcomes:
measure: Recorded abdominal distension in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded abdominal discomfort in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded abdominal meteorism in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded flatulence in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded borborygmi in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded nausea in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded belching in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded asthenia in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded headache in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded "empty- head" feeling in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded attention deficity in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded vomiting feeling in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Recorded heartburn in a diary using a 11-points Numeric Rating Scale (NRS)
timeFrame: 24 h
measure: Number of evacuations recorded in a diary
timeFrame: 24 h
measure: Recorded stool consistency in a diary using a 7- point Bristol Stool Form Scale
timeFrame: 24 h
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Policlinico San Matteo Pavia Fondazione IRCCS
Study officials:
References: