Condition category
Digestive System
Date applied
19/10/2020
Date assigned
23/10/2020
Last edited
20/10/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that over 5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. Recently, in many countries, gelatine tannate is being marketed for the treatment of acute gastroenteritis. The combination of gelatine tannate with tyndallized probiotics seems to offer an advantage over live probiotics for the treatment of chronic diarrhoea as it is intended to restore the physiological function of the intestinal wall as well as to prevent and alleviate dysbiosis (microbial imbalance) including digestive disorders as diarrhoea and other related symptoms such as bloating and abdominal tension, being effective within the first 12 hours. This study aims to assess the effectiveness and safety of gelatin tannate and tyndallized acid lactic bacteria in the treatment of adults with chronic diarrhoea with dysbiosis.

Who can participate?
Adults with chronic diarrhoea

What does the study involve?
Participants will be randomly allocated to group A or group B. One group will receive gelatin tannate and tyndallized acid lactic bacteria and the other placebo (dummy) tablets twice per day for 28 days.

What are the possible benefits and risks of participating?
This treatment could be very useful for the treatment of chronic diarrhoea caused by dysbiosis by reducing the symptoms associated with this diagnosis. To date, no adverse reactions to the study product have been reported.

Where is the study run from?
The study is conducted from Noventure S.L. (Spain), through the local Romanian representative

When is the study starting and how long is it expected to run for?
September 2020 to February 2022

Who is funding the study?
Noventure S.L. (Spain)

Who is the main contact?
Alina Iordache
alina.iordache@cebis-int.com

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Alina Iordache

ORCID ID

http://orcid.org/0000-0002-5931-0463

Contact details

CEBIS International
Helios Business Center (HBC)
47 Theodor Pallady Str.
Bucureşti (Sectorul 3)
032258
Romania
+40 (0)732225878
alina.iordache@cebis-int.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CBSNOV26022020

Study information

Scientific title

A randomized, double-blinded, placebo-controlled, clinical trial investigating the efficacy and safety of gelatin tannate and tyndallized acid lactic bacteria vs placebo administered to adult patients with chronic diarrhoea with dysbiosis

Acronym

RESTATE

Study hypothesis

Gelatin tannate and tyndallized acid lactic bacteria are safe and improve the major symptoms of chronic diarrhoea vs placebo.

Ethics approval

1. Approved 20/07/2020, Bulgarian Drug Agency (8, Damyan Gruev Str., 1303, Sofia, Bulgaria, + 359 (0)2 8903555; bda@bda.bg), ref: ИАЛ-29402/20.07.2020
2. Approved 04/09/2020, Republic of Bulgaria, Ministry of Health, Ethics Committee for Clinical Trials (8, Damyan Gruev Str., 1303, Sofia, Bulgaria; +359 (0)2 8903435; bda@bda.bg), ref: ЕККИ/СТ-0783
3. Approved 01/10/2020, Romanian Committee for the Bioethics of Medicines and Medical Devices (19-21 Stefan cel Mare Str., District 2, Bucharest, Romania; +40 (0)21/2102880; comisie@bioetica-medicala.ro), ref: 3DM / 16.07.2020

Study design

Double-blind placebo-controlled randomized multicenter study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Chronic diarrhoea

Intervention

Visit 1 – Baseline visit
Visit 2 (Day 8) – Randomization visit
Visit 3 (Day 36) – End of treatment/end of study

Patients fulfilling the inclusion criteria will be recruited by gastroenterologists, internal medicine, and/or family doctors during ambulatory visits and/or during the hospitalized period. The screening period will start after obtaining the signed Informed Consent Form for each subject. Subjects who meet the eligibility criteria will be randomly assigned to group A or group B, in a 1:1 ratio, at Visit 2 (Day 8). One group will receive gelatin tannate and tyndallized acid lactic bacteria and the other placebo tablets. The dosage schedule for the study products will be two tablets twice per day for 28 consecutive days.

Intervention type

Mixed

Phase

Drug names

Primary outcome measure

1. Pain relief assessed using an 11-point scale from 0-10 in the subject diary on each day of the treatment period
2. Major symptoms of chronic diarrhoea (abdominal pain and distension) assessed on a 7-point Likert scale in the subject diary on each week of the treatment period
3. Proportion of subjects who tested negative for dysbiosis using PCR at baseline and day 36
4. Relief of symptoms assessed through the subject diary on each week of the treatment period. Additionally, the timing for the beginning of the clinical response will be also evaluated.
5. Stool consistency assessed on the Bristol scale through the subject diary on each week of the treatment period
6. BMI, abdominal girth and weight measured using physician evaluation at baseline and day 36
7. Bowel movement frequency assessed using an 11-point scale from 0-10 in the subject diary on each day of the treatment period

Secondary outcome measures

Safety assessed by:
1. No. of subjects that discontinued treatment due to adverse events at day 36
2. No. of subjects that experienced an adverse event and severity at day 36
3. Proportion of subjects who presented no improvement in clinical condition at day 36

Overall trial start date

04/09/2020

Overall trial end date

28/02/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Chronic diarrhoea defined as a morbid process of at least 4 weeks of duration and a change in stool consistency to loose or liquid form (types 5-7, according to the Bristol Stool Chart) and/or an increase in the frequency of evacuations (≥3 in 24 h)
2. Patients diagnosed with irritable bowel syndrome or functional diarrhoea (according to the Rome IV criteria) or biliary acid malabsorption
3. Patients will be included if they record, during the week before randomization, an average score for stool consistency of ≥5.5 or a score of ≥5 on the Bristol Stool Chart for at least 5 days and an average score of ≥3.5 or a score of ≥3 for at least 5 days in the number of bowel movements
4. Participants will be tested at baseline for functional intestinal dysbiosis (Aliment Pharmacol Ther 2012;35(7):828-38), as demonstrated by real-time PCR analysis of faecal samples
5. Ability to sign the informed consent form

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

190

Participant exclusion criteria

1. Use of antibiotics, gelatin tannate, diosmectite, probiotics, racecadotril, zinc, opioids, or any other drugs or medical devices know to alter gastrointestinal motility or secretion within 4 weeks prior to enrolment
2. Chronic diarrhoea caused by cystic fibrosis, coeliac disease, food allergy, diabetes
3. Chronic diarrhoea caused by lactose, fructose, or sorbitol intolerance
4. Immunodeficiencies
5. Abnormal thyroid function, a history of alcohol abuse or binge drinking, pancreatitis, sphincter of Oddi dysfunction, cholecystitis within the past 6 months, or known allergy to any of the components of the product or placebo
6. Pregnant or breastfeeding women
7. Patients receiving antidepressant medications will be eligible to participate in the study, provided that dosing has been stable for 12 weeks or longer before enrollment
8. If needed, discontinuation or modification of the treatment may be considered at the discretion of the physician

Recruitment start date

23/11/2020

Recruitment end date

31/12/2021

Locations

Countries of recruitment

Bulgaria, Romania

Trial participating centre

Cluj-Napoca County Emergency Clinical Hospital - Internal Medicine, Section III
4-6 Clinicilor Street, Cluj-Napoca
Cluj-Napoca
400 000
Romania

Trial participating centre

Algomed Polyclinic
4 Lucian Blaga Str.
Timisoara
300 002
Romania

Trial participating centre

Medical office "Dr. Cristian Gainaru SRL"
23 Principala Str.
Corbii Mari, Dambovita
137135
Romania

Trial participating centre

Medical office “Dr. Fratila SRL”
4 Remenyik Sandor Str.
Oradea
410167
Romania

Trial participating centre

Medical Center Prolet EOOD
25 Olimpi Panov Str., fl. 2
Ruse
7000
Bulgaria

Trial participating centre

BROD - Ambulatory Practice for Primary Medical Care EOOD
23 Petko D. Petkov Str.
Plovdiv
4000
Bulgaria

Trial participating centre

Ambulatory Practice for Primary Outpatient Medical Care SANA OOD
8 Akademic Stefan Mladenov, Str.
Sofia
1700
Bulgaria

Trial participating centre

Ambulatory Practice for Primary Outpatient Medical Care SANA OOD
8 Akademic Stefan Mladenov, Str.
Sofia
1700
Bulgaria

Trial participating centre

Individual Ambulatory Practice for Primary Medical Care Stanchev Medical
3 Panteley Genov Str., fl. 1, office 2
Plovdiv
4000
Bulgaria

Trial participating centre

Individual Ambulatory Practice for Primary Medical Care Dr. Georgi Tsigarovski EOOD
7 Gergana Str., fl. 1, office 3
Plovdiv
4001
Bulgaria

Sponsor information

Organisation

Noventure S.L.

Sponsor details

Calle Consell de Cent 333
Barcelona
08007
Spain
+40 (0)737 640 721
alina.iordache@cebis-int.com

Sponsor type

Industry

Website

https://www.noventure.com/

Funders

Funder type

Industry

Funder name

Noventure S.L.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal. Additional documents will be provided at a later date.

IPD sharing statement
The data will be collected under the study confidentiality and for the study purpose only, according to the approved informed consent form. The study data will be archived according to the sponsor requirements and local regulatory requirements.

Intention to publish date

01/09/2022

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

20/10/2020: Trial's existence confirmed by the Republic of Bulgaria Ministry of Health Ethics Committee for Clinical Trials.