The Effect of the Multispecies Probiotic Ecologic 825 Versus Placebo in Ulcerative Colitis Patients (CUPIDO)

RATIONALE: The underlying etiology in inflammatory bowel diseases such as Ulcerative Colitis is not yet fully understood. Studies suggest a relation between higher intestinal permeability and aberrant changes of the epithelium. Dysbiosis of the intestinal microbiota might be the cause. Probiotics may restore the balance of the intestinal microbiota. In theory this could improve intestinal permeability and therefore reduce disease activity and maintain remission in patients with Ulcerative Colitis.

OBJECTIVE: To investigate whether a specifically designed multispecies probiotic mixture (ecologic 825®), as adjuvant therapy, can contribute to an improvement of intestinal permeability, microbiota composition, disease activity and inflammatory markers in ulcerative colitis.

STUDY DESIGN: 12-wk placebo-controlled randomized double-blind intervention with 2 parallel arms.

STUDY POPULATION: Adults diagnosed with left sided Ulcerative Colitis or Pancolitis in remission or mild stage of the disease. For inclusion of the patients the Patient Simple Clinical Colitis Activity Index (P-SCCAI) will be used.

INTERVENTION: Patients will receive either two daily dosages of 3 g of Ecologic® 825 or two daily doses of 3 g of the placebo, containing only the carrier material (both produced by Winclove Probiotics).

MAIN STUDY PARAMETERS/ENDPOINTS: Main study parameter is intestinal permeability measured by several techniques: the lactulose/mannitol absorption test (L/M test), LPS levels in blood serum and faecal zonulin. Secondary, inflammation will be measured from faecal calprotectin and blood c-reactive protein (CRP) levels. Furthermore samples will be stored to measure cytokine concentrations in serum and to analyse the microbial composition of the faecal samples using the HITchip. For the disease related quality of life the irritable bowel disease questionnaire (IBD-Q) and SF-36 will be used. All parameters will be measured at three time points; t=0, t=6 and t=12 weeks.

Study Overview

• Status: Suspended
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Ecologic 825

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Ede, Netherlands
    • Gelderse Vallei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed Ulcerative Colitis (left sided UC or pancolitis)
• Age 18-65 (because microbiota change at older age)
• Stable disease activity (clinical remission with CRP levels <10mg/L and calprotectin <100 ug/g) as measured at baseline
• Mild disease activity (P-SCCAI <5)
• Mesalazine medication as only medication for UC with a maximum intake of 2.4 g/day

Exclusion Criteria:

• History of intestinal surgery that might interfere with the outcome of the study
• Diabetes Mellitus (medication dependent)
• Current use of antibiotics
• Current use of corticosteroids (30 days prior to the first baseline measurement).
• Treatment with other medication besides mesalazine (NSAIDs, topical or systemic steroids, immunosuppressive drugs or aspirin) one week prior the first baseline measurement.
• Use of other pre- and probiotics and not willing to stop these 2 weeks before the intervention period
• Hypersensitivity or allergy to milk protein, soy protein and gluten
• Alcohol abuse (male more than 14 servings a week, female more than 7 servings a week)
• Female patients: currently pregnant or breast-feeding or intending to become pregnant during the study
• Patients foreseen to need GI surgery during the study period
• Patients with a history of cancer

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotics; Multispecies probiotic product Ecologic 825, 2x10-9 colony forming units per gram, 6 grams per day.	Dietary supplement: Ecologic 825; Multispecies probiotic product, 2.5 x10E9 colony forming units per gram, 6 grams a day; Other Names: PRO.IB
Placebo Comparator: Placebo; Similar in appearance as the probiotics, but not containing any bacteria.	Dietary supplement: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal permeability measured by the Lactulose Mannitol test (L/M test)	Measured by the Lactulose Mannitol ratio in urine (L/M test)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
blood CRP levels	inflammatory marker	6 and 12 weeks
fecal calprotectin levels	marker of intestinal inflammation	6 and 12 weeks
Quality of life (measured by IBD-Q and SF36)	Disease related quality of life will be measured by IBD-Q and SF36	6 and 12 weeks
Intestinal permeability measured by the Lactulose Mannitol test (L/M test)	Measured by the Lactulose Mannitol ratio in urine (L/M test)	6 weeks
Lipopolysaccharides levels in blood	A marker for intestinal permeability and inflammation	6 and 12 weeks
Intestinal permeability measured by faecal zonulin levels	Measured by faecal zonulin levels	6 and 12 weeks
microbiota composition	measured by human intestinal tract (HIT-chip) microarray	6 and 12 weeks
interferon gamma levels	measured in plasma samples	6 and 12 weeks

Collaborators and Investigators

• Sponsor: Wageningen University
• Investigators: Principal Investigator: Nicole De Roos, PhD, Wageningen UR

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: February 6, 2015
• First Posted (Estimate): February 12, 2015

Study Record Updates

• Last Update Posted (Estimate): August 28, 2015
• Last Update Submitted That Met QC Criteria: August 27, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: NL46674.081.13