National Multicenter Interventional Study Aimed at Evaluating the Effect on the Intestinal Microbiota in Chronically Frail Patients Who Share Alterations in Intestinal Function.

Study Overview
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Brief Summary
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The objective of the study will be to understand whether a supplementation of the diet with an active symbiotic, i.e. characterized by a mix of probiotics and a specially selected fiber with prebiotic activity combined with a vegetable extract with beneficial activities on carbohydrate and lipid metabolism, can reduce the relative inflammatory potential and improve absorption, intestinal motility and bowel habit of patients with various pathological conditions, such as ALS, ADHD and bronchial asthma.

Detailed Description
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Clinical survey conducted for research and study purposes, multicenter, focusing on ALS patients, elderly patients with chronic diseases, and pediatric patients with neurodevelopmental disorders. For each of the diseases treated, patients will be randomized into the two treatment arms (Study Group, GS; Control Group, GC) according to a block randomization, with a block size of 4 and an allocation ratio of 1:1. The randomization will be double-blind. Study Group or GS: These subjects will be given an active symbiotic preparation consisting of two sticks of 1500mg each and of different colors. Control group or GC:These subjects will be given a passive symbiotic preparation again consisting of two sticks of 1500mg each.

Official Title
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'sPATIALS3' - National Multicenter Randomized Controlled Interventional Study, Comparing an Active Symbiotic and a Passive Symbiotic Aimed at Evaluating the Effect on the Intestinal Microbiota and on the State of Health and Well-being of Various Types of Chronically Frail Patients United by Alterations of Intestinal Function.

Conditions
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Adhd, ALS, Bronchial Asthma

Intervention / Treatment
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* Dietary Supplement: Prebiotic fiber
* Dietary Supplement: Dietary fiber
* Dietary Supplement: Probiotic


Participation Criteria
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Eligibility Criteria
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Population 1 : ALS Inclusion Criteria: Age at enrollment ≥18 years; ALS diagnosis defined or probable according to El Escorial criteria (Brooks et al., 2000); Respiratory function with FVC% >50%. Exclusion Criteria: Subjects unable to give informed consent to the study; presence of psychiatric disease or severe cognitive impairment; presence of tracheotomy; presence of severe pre-existing gastrointestinal disease (e.g., ulcerative rectocolitis; Crohn's disease). Population 2: ADHD Inclusion Criteria: children between 6 and 16 years old children with ADHD, diagnosed with DSM-5 criteria and in accordance with the protocol shared by the Regional ADHD Reference Centers Lombardy. Exclusion Criteria: presence of intellectual disability (QIT<70), presence of neurological diseases, epilepsy presence of genetic syndromes treatment with drug therapies. Co-diagnosis with other psychiatric or neurodevelopmental disorders (i.e. Autism, Anxiety, Depression etc) will not be considered a criterion of exclusion. Population 3: Bronchial Ashtma Inclusion Criteria: adults above 18 years of age diagnosed with Bronchial Ashtma following ERS-ETS criteria Exclusion Criteria: life expectancy less than 18 months active respiratory infections cognitive disorders that prevent participation to the study (MMS <24)
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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic + fiber<br>These subjects will be given a passive symbiotic preparation again consisting of two sticks of 1500mg each to be taken once a day: Purple Sachet - Prebiotic - Composed of 500mg acacia fiber (Fibregum®) with high prebiotic activity and 500mg mai starch. Excipients and flavorings. White Sachet - Probiotic - 30 Billion bacterial strains Lactobacillus plantarum LP (PBS067- EU Collection DSM 24937), Lactobacillus acidophilus L. | Dietary Supplement: Dietary fiber<br>* Fibregum non-active fiber product<br>Dietary Supplement: Probiotic<br>* Defense Plus probiotic complex<br>|
| Experimental: Probiotic + Prebiotic<br>These subjects will be given an active symbiotic preparation consisting of two differently colored sticks of 1500mg each to be taken once a day: Purple Sachet - Active Prebiotic - 500 mg of Fibregum®, a slow-fermenting prebiotic fiber and 500 mg of standardized extract of pigmented Zea Mays L fruit, rich in anthocyanins and polyphenols. Excipients and flavorings. White Sachet - Probiotic - 30 Billion Bacterial Strains Lactobacillus plantarum LP (PBS067- EU Collection DSM 24937), Lactobacillus acidophilus LA (PBS066 - EU Collection DSM 24936) and Bifidobacterium animalis subsp. lactis BL (BL050 - Eu Collection DSM 25566). | Dietary Supplement: Prebiotic fiber<br>* Moradyn active prebiotic fiber product<br>Dietary Supplement: Probiotic<br>* Defense Plus probiotic complex<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in levels of Short Chain Fatty Acids (SCFA) | Evaluation of pre-post treatment variation of the level of specific SCFAs (acetic acid, propionic acid, butyric acid and valeric acid) both within the group of the treated and between the group of treated patients and the placebo group. | Before and After 3 months of intervention | 
| Change in levels of branched chain fatty acids (isobutyrate and isovalerate) | Evaluation of the pre-post nutritional variation of the level of branched chain fatty acids (isobutyrate and isovalerate) between the group of treated patients and the placebo group | Before and After 3 months of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conners' Parent Rating Scale-Revised - scale H (ADHD Index) | The score of subscale H on the Conners' Parent Rating Scale-Revised allows to identify children / adolescents at risk of ADHD. The score is a T-score with mean 50 and deviation standard 10 in the general population Minimum score = 35 Maximum score = 100 Higher scores correspond to greater severity: >70 very atypical 66-70 moderately atypical 61-65 slightly atypical 56-60 borderline range ≤ 55 non problematic | Before and After 3 months of intervention | 
| Conners' Parent Rating Scale-Revised - Scale K (total CGI) | The score of subscale K on the Conners' Parent Rating Scale-Revised reflects a general problem behavior. A high score indicates a hyperactivity problem, often associated with other problem areas. The score is a T-score with mean 50 and deviation standard 10 in the general population Minimum score = 35 Maximum score = 100 Higher scores correspond to greater severity: >70 very atypical 66-70 moderately atypical 61-65 slightly atypical 56-60 borderline range ≤ 55 non problematic | Before and After 3 months of intervention | 
| Conners' Parent Rating Scale-Revised - Scale B (attention problem) | Higher scores in the subscale B on the Conners' Parent Rating Scale-Revised are are related to lower learning abilities and difficulties in sustaining prolonged levels of attention. The score is a T-score with mean 50 and deviation standard 10 in the general population Minimum score = 35 Maximum score = 100 Higher scores correspond to greater severity: >70 very atypical 66-70 moderately atypical 61-65 slightly atypical 56-60 borderline range ≤ 55 non problematic | Before and After 3 months of intervention | 
| Conners' Parent Rating Scale-Revised - Scale C ( hyperactivity) | Higher scores in the subscale C on the Conners' Parent Rating Scale-Revised are indicative of higher levels of restlessness and impulsivity. The score is a T-score with mean 50 and deviation standard 10 in the general population Minimum score = 35 Maximum score = 100 Higher scores correspond to greater severity: >70 very atypical 66-70 moderately atypical 61-65 slightly atypical 56-60 borderline range ≤ 55 non problematic | Before and After 3 months of intervention | 
| Amyotrophic Lateral Sclerosis Functional Rating Scale - revised (ALSFRS-r) | Functional assessment of disease state. maximum score 4 - minimum score 0; for 12 items. indicates normal condition - 0 corresponds to a degree of major severity. The total score can range from a minimum of 0 to a maximum of 48; a score <29 indicates rapid disease progression. | Before and After 3 months of intervention | 
| Gastrointestinal Symptom Rating Scale (GSRS) | Represents the main symptoms complained about by the patients. maximum score Unbearable disturbances - minimum score No disturbance; for 15 items. The scores follow these directions: No disturbance Mild disturbances Bearable disturbances Moderate disturbances Somewhat severe disturbances Severe disturbances Unbearable disturbances | Before and After 3 months of intervention | 
| Forced Expiratory Volume - 1st second (FEV1) | Expired Volume measured after 1 second during pneumotachography exam | Before and After 3 months of intervention | 
| Forced Vital capacity (FVC) | Inspired maximal volume during pneumotachography exam | Before and After 3 months of intervention | 
| Asthma control test score | Test containing items related to cough and breathlessness, validated in asthmatic subjects Test contains five items scored on a 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled) | Before and After 3 months of intervention |