Oral Administration of Actitan-F in Paediatric Diarrhoea

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Chronic Diarrhoea of Infants and/or Young Children

Intervention / Treatment
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* Device: Lenodiar Pediatric
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenodiar Pediatric<br>Medical Device | Device: Lenodiar Pediatric<br>* Medical Device made of natural substance<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Product appearance similar to verum without clinical efficacy<br>|

What is the study measuring?
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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) |