Oral Administration of Actitan-F in Paediatric Diarrhoea

Efficacy and Safety of Oral Administration of the Plant-based Complex Actitan-F in the Management of Chronic Paediatric Diarrhoea: a Double-blind, Placebo-controlled, Parallel-group Investigation

The goal of the study is to investigate the efficacy and safety of Lenodiar Pediatric (product under investigation) for the treatment of Chronic Diarrhoea (functional or post-infective diarrhoea) in children aged 1-5 years old, through a randomized, double blind, placebo-controlled clinical investigation

Study Overview

• Status: Recruiting
• Conditions: Chronic Diarrhoea of Infants and/or Young Children
• Intervention / Treatment: Device: Lenodiar Pediatric; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luca Franceschini, Ph. D; Phone Number: +39 3386794491; Email: lfranceschini@aboca.it

Study Locations

• Italy
  • Bergamo, Italy
    • Recruiting
    • Asst Papa Giovanni XXIII
    • Contact: Naire Sansotta, Dr
  • Catania, Italy, 95126
    • Recruiting
    • Azienda Ospedaliera Cannizzaro, UOC Pediatria e PS Pediatrico
    • Contact: Antonella Di Stefano, Professor; Phone Number: +39957264334; Email: vitantonelladistefano@gmail.com
  • Chieti, Italy
    • Recruiting
    • Policlinico "SS. Annunziata" Clinica Pediatrica Via dei Vestini, Località colle dell'Ara 66100, Chieti
    • Contact: Francesco Chiarelli, Professor; Email: chiarelli@unich.it
  • Firenze, Italy, 50139
    • Recruiting
    • IRCCS AOU Meyer SOC Gastroenterologia e Nutrizione, Viale Gaetano Pieraccini 24
    • Contact: Paolo Lionetti, Professor; Email: paolo.lionetti@unifi.it
  • Milano, Italy, 20135
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo Presidio San Carlo, Ambulatorio di Gastroenterologia Pediatrica
    • Contact: Diana Ghisleni, Professor; Phone Number: +02/8184.4171; Email: diana.ghisleni@asst-santipaolocarlo.it
  • Napoli, Italy, 80138
    • Recruiting
    • Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli", I Clinica Pediatrica
    • Contact: Caterina Strisciuglio, Professor; Phone Number: 081 566 5445; Email: caterina.strisciuglio@unicampania.it
  • Palermo, Italy, 90134
    • Not yet recruiting
    • ARNAS Ospedale Civico e Benfratelli G Cristina e M Ascoli, Pediatria ad Indirizzo Gastroenterologico
    • Contact: Francesca Cavataio, Professor; Phone Number: +39916666197; Email: francesca.cavataio@arnascivico.it
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo, Pediatria
    • Contact: Silvia Maria Elena Caimmi, Professor; Phone Number: +390382502923; Email: gl.marseglia@smatteo.pv.it
  • Perugia, Italy
    • Not yet recruiting
    • Ospedale S. Maria Della Misericordia
    • Contact: Rita Cozzali, Dr
  • Pistoia, Italy, 51100
    • Recruiting
    • Ospedale San Jacopo di Pistoia, SOC Pediatria
    • Contact: Rino Agostiniani, Professor; Phone Number: +39573367379; Email: rinoagostiniani@gmail.com
  • Roma, Italy
    • Not yet recruiting
    • U.O. di Gastroenterologia e Riabilitazione Nutrizionale Ospedale Pediatrico Bambin Gesu Piazza S. Onofrio, 4 00165, Roma
    • Contact: Antonella Diamanti, Professor; Email: antonella.diamanti@opbg.net
  • Italia
    • Napoli, Italia, Italy, 80131
      • Recruiting
      • Azienda Ospedaliera Universitaria "Federico II",
      • Contact: Annamaria Staiano, Professor; Phone Number: +39817462679; Email: staiano@unina.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children of either sex aged between 1-5 years (inclusive);

• Diagnosis of chronic diarrhoea due to the following conditions:

  • Functional gastrointestinal disorder fulfilling Rome IV Criteria*
  • or
  • Functional gastrointestinal disorder fulfilling modified Rome IV Criteria **
  • or
  • Post-infectious diarrea with daily painless, recurrent passage of three or more large, unformed stools
• Parents/legal guardians*** availability to fill on a daily basis the electronic daily diary by a smartphone/tablet.
• Parents/legal guardians have given a written informed consent for participation in the investigation at the time of enrolment or before. The parent/legal guardian should also have agreed to bring the child for the visits scheduled in the protocol and to provide the requested information during the telephonic follow-up visit;
• Parents/legal guardian able to understand the full nature and the purpose of the investigation, including possible risks and side effects, able to cooperate with the Investigator and to comply with the requirements of the entire investigation (ability to attend all the planned investigation visits according to the time limits included) based on Investigator's judgement;

• Willingness not to make diet and lifestyle significant changes during the trial.

  • Rome IV criteria of functional diarrhoea (Neonate and Toddlers below 5 years), must include all of the following:

    • Daily painless, recurrent passage of four or more large, unformed stools
    • Symptoms last more than 4 weeks
    • Onset between 6 and 60 months of age

    • No failure-to-thrive if caloric intake is adequate

      ** Modified Rome IV criteria of functional diarrhoea (Neonate and Toddlers below 5 years), must include all of the following:

    • Daily painless, recurrent passage of three or more large, unformed stools
    • Symptoms last more than 2 weeks (Nelson Pediatric Texbook 21st Edition, Chronic diarrhea)
    • Onset between 6 and 60 months of age
    • No failure-to-thrive if caloric intake is adequate

    • These criteria have been modified in order to align the study to the functional diarrhoea condition in the real life.

      • Parent is the child's biological or adoptive parent. Legal guardian is defined as an individual who was authorized under applicable state or local law to consent on behalf of a child to general medical care, when general medical care includes participation in research. A guardian also meant an individual who was authorized to consent on behalf of a child to participate in research.

Exclusion Criteria:

• Carbohydrate malabsorption, diagnosed either clinically (2 weeks exclusion diet with resolution of symptoms) or with proper testing (breath test)*;
• Patients with any of the following chronic gastrointestinal disorders: inflammatory bowel disease, pancreatitis, chronic liver disease, eosinophilic oesophagitis, peptic ulcer disease, celiac disease, pseudo-obstruction, small bowel bacterial overgrowth, or Hirschsprung's disease
• Significant chronic health condition requiring specialty care (e.g., lithiasis, ureteropelvic junction obstruction, sickle cell, cerebral palsy, hepatic, hematopoietic, renal, endocrine, or metabolic diseases) that could potentially impact the child's ability to participate or confound the results of the investigation;
• Gastrointestinal blood loss;
• Recurrent or unexplained fevers;
• Developmental disabilities impairing ability to understand or communicate;
• History of hypersensitivity or allergy to investigational product;
• History of previous abdominal surgeries in the past 3 months;
• Known hypersensitivity to any of the components (active ingredients or excipients) of the investigational product;
• Conditions known to producing immunodeficiency (AIDS, other congenital immunodeficiency syndromes, drugs therapy with steroids, anticancer drugs, etc.);

• Patients who have received any of the following treatments within the 2 weeks before the baseline visit:

  • Agents specially developed for achieving adsorbing properties, e.g. kaolin, pectin, bismuth subsalicylate;
  • Treatments that modify intestinal secretions, e.g. racecadotril;
  • Treatments that modify intestinal motility, e.g. opiates, anti-cholinergic agents;
  • Systemic Antibiotics;
  • Antiemetic agents.
• Patients who have received probiotics and prebiotics within the 1 week before the baseline visit, unless they have been taken at stable dose (the use of probiotics and prebiotics in dairy food such as yoghurt, cheese, milk prior to the investigation is permitted);
• Parents/legal guardians' refusal or inability to give written informed consent to participate in the investigation;
• Parents/legal guardians who, in the opinion of the Investigator, are unable to fill up the electronic patient diary;

• Patients who have participated in any other clinical trial in the last 3 months prior to the start of the investigation.

  • Applicable only for patients with Functional gastrointestinal disorder fulfilling Rome IV Criteria.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Product appearance similar to verum without clinical efficacy
Experimental: Lenodiar Pediatric; Medical Device	Device: Lenodiar Pediatric; Medical Device made of natural substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in stool consistency averaged over the 2-week Treatment Period	Stool consistency will be assessed using the Bristol Stool Form Scale (BSFS) on a range from 1 (Hard Lumps) to 7 (Watery).	Up to 2 weeks vs Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change for daily daytime and nighttime stool consistency scores	Change for daily daytime and nighttime stool consistency scores assessed using the Bristol Stool Form Scale (BSFS) on a range from 1 (Hard Lumps) to 7 (Watery).	(Week1 to Week4) vs Baseline
Change for 24-hour abdominal pain scores	Abdominal Pain is scored on a five-point ordinal scale, with 0 meaning no pain, and 4 meaning a lot of pain.	(Week1 to Week4) vs Baseline
Change for daytime, nighttime, and 24-hour bowel movement frequency	Change for daytime, nighttime, and 24-hour bowel movement frequency	(Week1 to Week4) vs Baseline
Change for daytime, nighttime, and 24-hour urgency-free days	Change for daytime, nighttime, and 24-hour urgency-free days (only for patients who have removed the diaper and have received training toilet)	(Week1 to Week4) vs Baseline
Time to event, with the event defined as the first week in which a reduction ≥50% of loose or watery stools as compared to baseline occurs.	Time to event is defined as the time elapsed (days) from the date of randomization to the date of the first week in which a reduction ≥50% of loose or watery stools as compared to baseline occurs. This endpoint will be assessed through electronic diary.	through study completion, an average of 4 weeks
Use of other treatments (proportion of users) for diarrhea relief, evaluated by means of the electronic patient diaries;	Use of other treatments (proportion of users and quantity) for diarrhea relief, evaluated through a electronic patient diaries;	through study completion, an average of 4 weeks
Use of other treatments (quantity of other treatments) for diarrhea relief, evaluated by means of the electronic patient diaries;	Use of other treatments (proportion of users and quantity) for diarrhea relief, evaluated through a electronic patient diaries;	through study completion, an average of 4 weeks
Change in results of the Pediatric Quality of Life Questionnaires	Change in results of the Pediatric Quality of Life Questionnaires assessed through a validated questionnaire	Visit 1 (day 14); Visit 2 (day 28);
Change in results of the patient happiness using a weekly smiley likert scale	Parents/legal guardians will report, on a weekly basis, the happiness of the patients using a smiley face likert scale (Very happy; Happy; Slightly happy; Neutral; Slightly unhappy)	through study completion, an average of 4 weeks
Change in results in parent Quality of Life (100 mm VAS)	Change in results in parent Quality of Life using a 100 mm Visual Analogie Scale, ranging from "0" (corresponds to a quality of life "very low") and the value "100" (corresponds to a quality of life "very high")	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Time to event, with the event defined as the first day in which loose or watery stools are not observed.	Time to event is defined as the time elapsed (days) from the date of randomization to the date of the first day in which loose or watery stools are not observed.	through study completion, an average of 4 weeks
Change in patients' lifestyle	Change in patients' lifestyle assessed through a lifestyle questionnaire	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Time to event, with the event defined as the third day of the first consecutive three days in which diagnostic criteria for chronic diarrhoea are no more met.	Time to event is defined as the time elapsed (days) from the date of randomization to the date of the third of the first consecutive three days in which diagnostic criteria for chronic diarrhoea are no more met	through study completion, an average of 4 weeks
Change from baseline in stool consistency at day 3, day 7 and day 10.	Change from baseline in stool consistency at day 3, day 7 and day 10. Stool consistency will be assessed using the Bristol Stool Form Scale (BSFS) on a range from 1 (Hard Lumps) to 7 (Watery).	Baseline to day 3, day 7 and day 10
Adverse Event	Incidence of adverse events (AEs)	through study completion, an average of 4 weeks
Serious Adverse Event	Incidence of serious adverse events (SAEs)	through study completion, an average of 4 weeks
Adverse device effects	Incidence of adverse device effects (ADEs)	through study completion, an average of 4 weeks
Serious adverse device effects	Incidence of a serious adverse device effects (SADEs)	through study completion, an average of 4 weeks
Unexpected serious adverse device effects	Incidence of unexpected serious adverse device effects (USADEs)	through study completion, an average of 4 weeks
Early withdrawal rate due to AEs	Incidence of early withdrawal rate due to AEs, whether serious or not	through study completion, an average of 4 weeks
Safety Endpoints - early withdrawal rate due to ADEs	Incidence of early withdrawal rate due to ADEs, whether serious or not.	through study completion, an average of 4 weeks
Systolic/diastolic blood pressure	Change from baseline in clinical examination findings (systolic/diastolic blood pressure)	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Pulse	Change from baseline in clinical examination findings (pulse)	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Weight	Change from baseline in clinical examination findings (weight)	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Body Mass Index	Change from baseline in clinical examination findings (Body Mass Index)	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Waist circumference	Change from baseline in clinical examination findings (waist circumference)	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Faecal microbiota	Differences before and after treatment in the analyses of Faecal microbiota, collecting and analysing stool samples	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Faecal metabolomics	Differences before and after treatment in the analyses of Faecal metabolomics, , collecting and analysing stool samples.	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)
Micro RNA	Differences before and after treatment in the analyses of Micro RNA (miRNA) from mouth epithelial cells, , collecting and analysing buccal samples	Baseline to Visit 1 (day 14) and Visit 2 (day 28) and Visit 1 (day 14) to Visit 2 (day 28)

Collaborators and Investigators

• Sponsor: Aboca Spa Societa' Agricola
• Collaborators: IQVIA RDS; IQVIA Solutions

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: ABO-LENP-01/22

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No