Clinical Pilot Trial on the Effect of a Probiotic Fermented Drink on Antibiotic-associated Diarrhea (AAD)

A Randomized Double-blind Placebo-controlled Clinical Pilot Trial on the Effect of a Probiotic Fermented Drink on Antibiotic-associated Diarrhea (AAD) in Patients With Helicobacter Pylori Eradication Therapy

The aim of the study is to estimate the effect of a probiotic dairy drink on occurrence and duration of AAD and gastrointestinal symptoms during Helicobacter pylori (Hp) eradication therapy and during 4 weeks thereafter and calculating the sample size for a confirmatory study.

Study Overview

• Status: Completed
• Conditions: Antibiotic-associated Diarrhea
• Intervention / Treatment: Other: probiotic dairy drink; Other: acidified milk

Detailed Description

Helicobacter p. positive subjects aged ≥18 years with an indication for Helicobacter pylori (Hp) eradication recommended by a gastroenterologist should be included in the study. Subjects should be willing to consume 2 servings of the study product per day for 6 weeks, and to undergo an Hp eradication therapy for 14 days starting with the consumption period.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24118
      • CRC Clinical Research Center Kiel

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Individuals, both genders, aged ≥ 18 y
• Helicobacter p. infected individuals, to which eradication therapy has been recommended by gastroenterologists
• Willingness to undergo the Helicobacter p. eradication therapy
• Willingness to abstain from food and supplements containing probiotics, prebiotics and fermented products except the study product
• Written informed consent

Exclusion Criteria:

• Subjects currently enrolled in another interventional trial
• subjects having finished another interventional trial within the last 4 weeks before inclusion
• incapacity to comply with the study protocol
• allergy or hypersensitivity to any component of the test product (allergy against milk protein)
• allergy or hypersensitivity to any component of the eradication therapy (e.g. penicillin allergy)
• acute GIT infections
• chronic inflammatory bowel diseases (IBD)
• irritable bowel syndrome (IBS)
• any episode of diarrhea according to WHO criteria during the last 4 weeks before inclusion
• history of lactose intolerance
• severe chronic disease (cancer, malabsorption, malnutrition, severe chronic inflammatory diseases (except chronic gastritis), renal, hepatic or cardiac diseases, artificial cardiac valve, COPD, respiratory insufficiency)
• history of active or persistent hepatitis B and C
• known congenital, acquired or iatrogenic immunodeficiency (e.g. HIV, chemotherapy, immunosuppression)
• systemic treatment with antibiotics during the last 4 weeks before inclusion
• systemic treatment likely influencing absorption, metabolism and excretion of food ingredients (metoclopramide, laxatives, body weight management and/or medication etc.)
• systemic treatment likely interfering or influencing effectiveness of the eradication drugs used e.g. ergotamine, statins, clopidogrel
• regular medical treatment including OTC, which may have impact on the study aims (e.g. probiotics, antibiotic drugs, laxatives etc.)
• severe neurological, cognitive or psychiatric diseases
• surgery or intervention requiring general anaesthesia within 2 months before the study
• vegan
• eating disorders (e.g. anorexia, bulimia)
• present alcohol and drug abuse
• pregnancy or lactation
• legal incapacity

• blood parameters:

  • Hb < 12 g/dL
  • liver transaminases (ALT, AST) > 2-fold increased
  • serum creatinine out of the normal range
• subjects who are scheduled to undergo hospitalization during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verum; 2 bottles (á 65ml) of a probiotic dairy drink consumed daily for 6 weeks	Other: probiotic dairy drink; Other Names: verum
Placebo Comparator: Placebo; 2 bottles (á 65ml) of a dairy drink containing chemically acidified milk without bacterial strains consumed daily for 6 weeks	Other: acidified milk; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of antibiotic-associated diarrhea (AAD)	Occurrence of antibiotic-associated diarrhea (AAD) (as defined by number of subjects with diarrhea within the intervention period of 6 weeks after starting antibiotic treatment; diarrhea is defined according WHO	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulated duration of antibiotic-associated diarrhea (AAD)	Number of days with diarrhea within the intervention period	6 weeks
Gastrointestinal Symptom Rating Scale	Standardized questionnaire according Dimenäs et al.	6 weeks
Cumulative sverity of antibiotic-associated diarrhea (AAD)	Sum of the values (obtained by transformation of Bristol stool form types) of all stools during days with diarrhea (transformation of Bristol scale types is defined: type 1 to 4 = 0; type 5 = 1; type 6 = 2 and type 7 = 3)	6 weeks

Collaborators and Investigators

• Sponsor: Clinical Research Center Kiel GmbH
• Collaborators: Yakult Honsha Co., LTD
• Investigators: Study Chair: Chiyuki Kajita, Yakult Europe BV

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2016
• Primary Completion (Actual): December 23, 2016
• Study Completion (Actual): April 26, 2017

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimate): April 21, 2016

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Probiotics, Antibiotics, AAD, Helicobacter p.
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: 14DE-KIEL-HPAAD1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO