Scientific Evidence

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure.

METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed.

RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8–5.0; omeprazole 8.2, 4.8–11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm.

DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Policaptil Gel Retard® (PGR), a natural fiber-based molecule, has been shown to prevent weight gain and ameliorate insulin-resistance indices in obese children and adolescents. The aim of this study was to compare the effects of 12 weeks of low calories and low glycemic index (LC-LGI) diet associated or not with the intake of PGR on anthropometric, bioimpedance, and metabolic parameters. Data from 20 obese adult subjects (10 per group) were analyzed. An LC-LGI diet with or without PGR intake reduced weight, BMI, and waist circumference. PGR intake elicited a reduction in fasting plasma insulin and insulin resistance index together with an improvement in insulin sensitivity

Introduction: Metabolic syndrome (MetS) is increasingly common in adults as well as in children and adolescents. However, preventing and treating MetS is one of the most pressing challenges for public health services worldwide. At present, the only approved treatments for MetS are dietary changes and physical activity, which are associated with a high rate of non-compliance. On the contrary, no drugs are licensed to treat metabolic syndrome although a number of drugs are used to treat individual metabolic abnormalities, which increases the risk of adverse events, particularly in children. Policaptil Gel Retard®(PGR), an oral macromolecule complex based on polysaccharides, has been demonstrated to significantly reduce body weight, peak blood glucose (BG) levels, insulin levels and lipid levels, providing an interesting non-pharmacological therapeutic option for MetS-associated metabolic abnormalities, especially in younger patients.
Aims: To review available studies on the use of PGR in children, adolescents or adults with obesity or metabolic syndrome.
Methods: A systematic search of electronic databases for PGR and MetS. A total of six studies were identified and included.
Results: Across four randomised clinical studies and one retrospective clinical study including a total of 359 obese children and adolescents with or without MetS and 157 overweight/obese adults with or without MetS and/or T2DM, a single dose of PGR resulted in a reduction in appetite and postprandial triglyceride levels in younger patients and in peak postprandial BG levels in adults. Decreased lipid levels were observed in adults following a normo-caloric diet who received PGR for 30 days. As a long-term treatment, in combination with a low-glycaemic index diet with or without metformin, PGR resulted in reduced body mass index and waist circumference, improved insulin sensitivity with reduction of glucose-metabolism abnormalities, increased insulin reserve and, finally, an improved circulating lipid profile, regardless of age. No safety issues were reported. Conclusions: Policaptil Gel Retard® is an effective and safe non-pharmacological approach to improving the treatment of
MetS-associated cardiovascular risk factors in children, adolescents and adults.

Introduction: Metabolic Syndrome (MS) is a pathologic condition characterized by Type 2 diabetes mellitus (T2DM), insulin resistance, abdominal obesity, hypertension, and hyperlipidemia. Until now, specific drugs such as metformin (MET) have been used to address its individual components; however, according to the recommendation of WHO, various plant extracts might be used as alternative medicines due to the side effects of pharmacologic agents. Policaptil Gel Retard® (PGR), a macromolecule complex based on polysaccharides which slows down the absorption rates of carbohydrates and fats, proved effective against glucose abnormalities. Our study aimed to verify the short-term efficacy and safety of PGR under real-life conditions. Methods: We evaluated both the 6-month changes in metabolic parameters in Italian patients with MS and T2DM, and the 10-year CV risk score (10-y-CV-RS) from the CUORE equation, competitively randomized to Policaptil Gel Retard (2172 mg before each main meal); Group A, n = 75, or Metformin (1500–2000 mg/day equally divided between the two main meals), and Group B, n = 75. Results: Fasting plasma glucose and HbA1c decreased significantly and similarly (p < 0.001) in the two groups. A significant decrease in BMI (-20% in the PGR group (p < 0.01), -14.3% in the MET group (p < 0.05)), % visceral fat, and UA levels was also apparent in both groups (p < 0.01). The opposite occurred for lipid profile, which improved significantly in the PGR group but remained unchanged in the MET group. Consequently, only the PGR group experienced a significant decrease in the 10-y-CV-RS (31.4 ± 8.0 vs. 19.7 ± 5.2, p < 0.0001), whereas this remained unchanged in the MET group (32.2 ± 3.3 vs. 30.5 ± 8.7; p n.s.). Conclusions: PGR could represent a suitable alternative to MET as a first-line treatment option, especially now that an ever-increasing number of people prefer natural products based on plant extracts. This is particularly pertinent given that, besides trying to avoid gastrointestinal side-effects as much as possible, patients might be sensitive to ecotoxicology-related problems involving plants and animals caused by the worldwide spread of environmental MET metabolites.

Background and Aim: Hemorrhoidal Disease (HD) is a chronic pathology and is fairly common in the general population. For this reason, conservative therapies need to be at the same time effective and tolerated. The topical medications available usually contain either a combination of local anesthetics with anti-inflammatories or muscle relaxants, thus addressing a single mechanism, if any, of those that underlie symptoms onset. As a consequence, evidence of efficacy of these drugs is currently limited and the needed tolerability and safety from a topical treatment of HD is not always evident. The aim of the present study was to evaluate efficacy and tolerability of a 100% natural ointment, a medical device made of substances, for the symptomatic treatment of HD. Methods: Symptomatic grade I or II HD patients with 0-100 VAS score for HD-related
discomfort ≥ 30 were treated for 10 days. Outcome measures included variation of HD subjective symptoms (discomfort, pain, itching and burning) and objective signs (bleeding and anal leakage) at day 3, 7 and 10, and the presence of prolapse after treatment. Statistical analysis: for the analysis of the primary endpoint (i.e. reduction of discomfort), missing data in the full analysis set (FAS) population were replaced using the “Last Observation Carried Forward” (LOCF) method. For the analyses of secondary endpoints, Poisson mixed model was used to evaluate symptom variation (VAS). Bleeding and anal leakage were recoded as negative or positive in two different variables (grade 1 and 2) derived from their frequency (i.e., for grade1, each of the clinical signs was considered Negative if the patient reported frequency was “Never”; recoded as Positive if any other frequency category was reported) and frequencies of positive patients in each grade were compared by Logistic Mixed model. Mixed models were used to take in account repeated data for the same subject. Missing values in quantitative data analysing by Mixed model were imputed by statistical interpolation. In analysing bleeding, anal leakage and presence of prolapse in FAS population, missing data where either replaced using the LOCF method or imputed as positive (i.e., worst case).
Results: 45 patients were enrolled. Data showed a significant reduction of discomfort in treated patients both during and after treatment (p<0.001 at all-time points evaluated), with a median VAS score decrease of 30 points after treatment when compared to baseline. The same significant reduction (p<0.001) was shown for all other symptoms either at the end of treatment or at earlier time points, both in PP and FAS populations. As for objective signs, a significant reduction was observed, at each time point compared to baseline, in the number of patients from the PP population positive for bleeding (p<0.001) and anal leakage (p<0.05). A similar evolution was shown in FAS population, where reduction was progressive over the 10-day treatment and statistically significant or almost significant irrespectively of imputation method used. In 6 out of 10 patients presenting prolapse at baseline, prolapse was no more evident after treatment. No treatment-related adverse events were registered.
Conclusion: The class IIb medical device made of substances under study is a valid, highly tolerated and safe therapeutic option in medical management of grade I and II HD. Trial
registration NCT03545724 2018.06.04.

Background: Polyethylene glycol (PEG) is recommended as first-line treatment of pediatric functional constipation. However, the oral route of administration is often poorly feasible in children mostly due to poor palatability. Promelaxin microenemas exert a topical evacuative action and may offer a valuable option in pediatric FC.
Aim: To assess whether Promelaxin microenemas would be non-inferior to PEG 4000 in young children with FC.
Methods: This is a randomized, open-label, multi-centric, non-inferiority trial enrolling infants and young children aged 6–48 months, with FC according to Rome III criteria. After 1 week of run in, children were randomized to 2 weeks of Promelaxin or PEG, followed by a 6-week on-demand treatment period. Primary endpoint was response rate to randomized treatment, with “response” defined as at least 3 evacuations per week and an average increase of at least one evacuation per week as compared to baseline. Safety, stool consistency and the analysis of fecal microbiota were secondary endpoints.
Results: Out of the 158 patients who entered the trial, 153 patients were treated (77 and 76, PEG and Promelaxin arm, respectively). In the primary analysis, the 95% confidence interval (CI) for the treatment's effect lay entirely above the non-inferiority margin in both Full Set (FAS) and Per Protocol (PP) analyses, providing evidence of the non-inferiority of Promelaxin vs. PEG 4000 [response rate difference: 16.5% (CI 1.55–31.49%) and 11.03% (CI −5.58 to 27.64%), FAS and PP analyses, respectively]. Mean compliance to the randomized treatment was >80% in both arms. Secondary endpoints did not significantly differ between the two arms, except for the average number of total days of on-demand treatment that was significantly lower in the Promelaxin arm [14.6 (12.7) vs. 9.8 (9.1), mean (SD); primary endpoint responders in PEG and Promelaxin arm, respectively; p = 0.027]. Microbiota evenness significantly increased in the PEG 4000 arm at V4 as compared to the Promelaxin arm (p < 0.05). In addition, at V5, patients treated with PEG showed a significantly decreased microbiota density as compared to patients treated with Promelaxin (p = 0.036).
Conclusions: Promelaxin microenemas are non-inferior to oral PEG in children with FC.

Background: Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. Aim: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet.
Subjects and methods: This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500–2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. Results: all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart.
Conclusion: For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.

Upper respiratory tract infection (URTI)-associated acute cough is the most common symptom both in children and adults worldwide and causes economic and social problems with significant implications for the patient, the patient's family, and the health care system. New pathogenic mechanisms in acute cough, including the urge to cough (UTC) mechanisms, have been recently identified. The brainstem neural network, pharyngeal sensory innervation, airway mechanical stimulation, inflammatory mediators, and postnasal drip actively participate in the onset and maintenance of acute cough and the urge to cough phenomenon. However, there is still no effective pharmacological treatment capable of interfering with the pathophysiologic mechanisms involved in URTI-associated acute cough. Moreover, severe adverse events frequently occur in administering such cough medications, mainly in children. New evidence has been provided concerning polysaccharides, resins, and honey as potential cough relievers with high antitussive efficiency, effect on the UTC, and minimal side effects.

The aim of this study is to test the hypothesis that the intake of Policaptil Gel Retard® (PGR) is able to affect appetite, metabolic and hormonal postprandial profile in obese children. 46 obese children were randomly assigned to treatment with PGR or placebo, in a double blind clinical trial. Two PGR tablets or placebo were given in fasting condition, before the ingestion of a mixed meal (15 kcal/kg lean body mass). Blood samples were taken at baseline and for 4 h, for measuring blood lipids, glucose, insulin, ghrelin, and glucagon like peptide-1 (GLP-1). Appetite was quantified using a visual analog scale. Children assuming PGR had a significantly lower increase of postprandial triglycerides (area under the curve (AUC): 3021 (2879) vs. 5038 (3738) mg × 240 min/Dl) and appetite (-234 (274) vs. 36 (329)) than children assuming placebo. The AUC of ghrelin was significantly lower after PGR ingestion, than after placebo (-8179 (8073) vs. -2800 (7579) pg × 240 min/mL). Blood glucose, insulin, non-esterified fatty acids (NEFA) and GLP-1 profiles were not significantly different in the two groups. In conclusion, a single intake of two tablets of PGR was associated with a significant reduction of appetite, ghrelin, and triglycerides in the postprandial period in obese children. Further investigation will assess if a chronic intake of PGR may affect body weight and glucose metabolism.

Background: AG is the most common cause of pediatric consultations among children between 2 and 5 years of age and it still leads to high mortality and morbidity. Its management is based on rehydration therapy, but this treatment is not effective in reducing duration of diarrhea. For this reason, other safer and less expensive interventions, which could be added to oral rehydration therapy, are of great interest.
Methods: A pilot, randomized, case-controlled trial was conducted in 60 children affected by AG (< 7 days) with mild-moderate dehydration, according to WHO recommendations, from1 year to 17 years old. Patients were divided into 2 Groups: Group 1 consisting of 30 children treated with Actitan F and standard oral rehydration (SOR); Group 2 consisting of 30 children who received only SOR. Both groups received treatment for seven days, respectively. Patients of Group 1 stopped for their own choice, SOR after the first 24 h and continued only with Actitan F.
Results: After 24 h of treatment, the median number of stools was 3.5 for Group 1, and 4 for Group 2. In Group 1 the difference between the number of stools at baseline (n = 5) and after 24 h of treatment (n = 3.5) was significant (p < 0.0001). At the end of treatment, the median duration of diarrhea in Group 1 was 5 days, compared with 4 days in the Group 2, this difference was not statically significant (p 0.48).
Conclusions: Oral administration of Actitan F associated with SOR seems safe and effective treatment in shortening the duration of AG in children. Further studies confirming these data are needed.