Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D).

OBJECTIVE: Irritable bowel syndrome with diarrhoea (IBS-D) is a common and challenging condition that significantly reduces quality of life. Enterosgel (polymethylsiloxane polyhydrate) is an intestinal adsorbent which sequesters harmful molecules and is safe and effective in acute infective diarrhoea. This randomised controlled multicentre trial aimed to investigate its safety and efficacy in patients with IBS-D. DESIGN: After a 2-week screening phase, participants were randomised into an 8-week double-blind phase, followed by an 8-week open-label and follow-up phase. Participants recorded stool consistency, pain and global symptoms in e-diaries and questionnaires. The primary outcome was the percentage of responders on a composite abdominal pain (≥30% decrease in the weekly score) and stool consistency (50% reduction in days per week with at least one stool of BSFS type 6 or 7) score during at least 4 weeks of the treatment period. RESULTS: 440 patients with IBS-D were randomised to the double-blind phase with 393 continuing to the open-label phase. The Primary outcome responder rate by intention-to-treat for enterosgel versus placebo was 37.4% vs 24.3% (OR 1.95, NNT 8, p=0.002). Enterosgel also improved stool consistency (48.5% vs 32.5%, p<0.0001) abdominal pain (53.3% vs 40.2%, p=0.003), stool frequency (treatment effect -0.32 (-0.62 to -0.02)) and urgency (treatment effect -0.59 (-0.85 to -0.33)). 60% of patients reported adequate relief of symptoms after open-label treatment. Adverse event frequency was similar in both groups, with no serious events attributable to enterosgel. CONCLUSION: Enterosgel is safe and effective in IBS-D, providing an alternative to the limited current treatment options. TRIAL REGISTRATION NUMBER: ISRCTN17149988.

Randomised, double-blind, placebo controlled multi-centre study to assess the efficacy, tolerability and safety of Enterosgel® in the treatment of irritable bowel syndrome with diarrhoea (IBS-D) in adults.

BACKGROUND: Irritable bowel syndrome (IBS) with diarrhoea (IBS-D) is a common and chronic condition that can significantly impair quality of life. The emergence of new drugs for IBS-D has been slow and there is a need for new treatments, including drug-free treatments, which are easy to use and suitable for different patient groups. Currently available drug-free treatments include Enterosgel®, an intestinal adsorbent approved for use in IBS-D and acute diarrhoea and available over-the-counter in the UK and 30 countries worldwide. The aim of this randomised, double-blind, placebo-controlled, multi-centre study is to test the efficacy and safety of Enterosgel® compared to placebo in symptomatic treatment in IBS-D. METHODS/DESIGN: We will recruit 430 participants with IBS-D from approximately 30 primary and secondary care sites in England. Participants meeting the required abdominal pain and stool consistency criteria over a 2-week screening period will be randomly allocated to receive blinded treatment (Enterosgel® or placebo) for 8 weeks. This will be followed by an 8-week open-label treatment phase with Enterosgel®. Participants will be allowed to adjust their daily dosage during both phases based on their symptoms. Participants will then return to standard care and those who responded to treatment will receive a follow-up call 8 weeks later. Co-medication with loperamide will be permitted and use recorded. The primary outcome measure is the percentage of participants defined as responders for abdominal pain and stool consistency during at least 4 weeks in the 8-week blinded phase. Secondary outcome measures include stool frequency, stool consistency, abdominal pain, bloating, urgency, adequate relief, questionnaire scores and rescue medication use. Exploratory outcomes will be assessed in subsets of participants including qualitative and quantitative data on faecal microorganisms and biomarkers and gut-related measurements from magnetic resonance imaging data. DISCUSSION: This is the first large scale randomised controlled trial investigating Enterosgel® in IBS-D. A study design with blinded phase followed by an open-label phase was chosen to encourage participation and study completion. Demonstrating that Enterosgel® is effective and safe in IBS-D could encourage adoption by patients and healthcare professionals and foster future clinical trials assessing its use in related conditions. TRIAL REGISTRATION: ISRCTN17149988. Prospectively registered on 14 November 2017.

Enterosgel for the treatment of adults with acute diarrhoea in a primary care setting: a randomised controlled trial.

BACKGROUND: Acute intestinal infections are common conditions causing high morbidity and mortality especially in the young and elderly, resulting in a significant burden on health service resources and the economy. Current National Institute for Health and Care Excellence guidance are fluid and nutritional management; however, this does not reduce the duration of diarrhoea and the challenge of treating diarrhoea itself remains. We investigated the efficacy, tolerability and safety of intestinal adsorbent Enterosgel (polymethylsiloxane polyhydrate) compared with standard care in adults with acute diarrhoea. METHODS: This was a randomised controlled trial enrolling 105 subjects to receive the medical device Enterosgel up to six times daily for up to 8 days with standard care (oral rehydration solution), or standard care alone. The primary endpoint was the duration of diarrhoea (hours) from randomisation to first non-loose stool in the Enterosgel versus control group. RESULTS: A total of 51 subjects were randomised into the Enterosgel group and 54 into the control group, after excluding missing data, the data from 43 subjects in each group were analysed. Duration of diarrhoea was significantly shorter in the Enterosgel group at 27 hours versus 39 hours in the control group (HR was 1.74 [95% CI 1.06 to 2.87]) (p=0.03). This yielded a number needed to treat value of 5. Enterosgel was well tolerated and safe with no serious adverse events. One serious diarrhoea-related event resulting in hospitalisation was reported in the control group. CONCLUSIONS: Enterosgel treatment was associated with a significant reduction in the duration of diarrhoea in adults with patient-reported acute diarrhoea, compared with standard care. These findings support the role of Enterosgel in acute diarrhoea especially in vulnerable groups where rapid resolution of symptoms is required. Reduction in symptom duration could translate to less healthcare costs and socioeconomic burden. TRIAL REGISTRATION NUMBER: ISRCTN20758708.

Pharmacognostical and preliminary phytochemical evaluation of Alysicarpus longifolius W. and A. Prodr.

Ayurveda, the science of life, deals with the drugs of animal, herbal, or mineral origin. Drugs of plant origin occupy more than 90% of the constituents of the Ayurvedic formulations used during treatment. Due to over exploitation and non-availability of medicinal plants, certain classical drugs are being substituted by locally available ethnomedicinal plants that are being claimed to possess similar activity by the tribal and local practitioners. The authentic source of Prishniparni is Uraria picta Desv. (Fabaceae) and is being substituted by Alysicarpus longifolius W. and A. Prodr. (Fabaceae) by some traditional healers of Gujarat (Saurashtra region). Both the plants are locally known by the names Samervo or Pithvan and both have similar characteristics with reference to leaves and flowers (inflorescence type). Pharmacognostical and Phytochemical evaluation of Alysicarpus longifolius W. and A. Prodr has been carried out and results are reported.

Pharmacognostical and Preliminary physicochemical evaluation of Triphaladi granules - A polyherbal Ayurvedic formulation.

Triphaladi Kwatha, a polyherbal Ayurvedic formulation, is recommended by Chakradatta and Yogaratnakara in the management of Prameha which has resemblance with type 2 diabetes mellitus. The present study deals with development of pharmacognostical and preliminary pharmaceutical profile of Triphaladi granules. The pH (5% aqueous extract) was 6.0, water-soluble extract 48.66% w/w, alcohol-soluble extract 33.91% w/w, ash value 5.97% w/w, and loss on drying at 105°C was 6.53% w/w. High performance thin layer chromatography were carried out after organizing appropriate solvent system in which maximum nine spots were distinguished and few of the Rf values were identical in the alcoholic extract.

A comparative pharmacognostical profile of Desmodium gangeticum DC. and Desmodium laxiflorum DC.

Shaliparni is one of the Laghupanchamoola ingredients. Desmodium gangeticum DC. is an accepted source of Shaliparni as per Ayurvedic Pharmacopoea of India (API). Desmodium laxiflorum DC. is the drug commonly used instead of D. gangeticum in the Saurashtra region. The study is an attempt to compare the above said two species on the basis of their pharmacognostical profiles. The macroscopy and microscopy of roots of both plants were studied as per standard procedures. Root powders of both Desmodium species used in the experimental study to ascertain its Rasa by dilution method. Both the species show the same Rasa and Anurasa i.e., Madhura and Kashaya and almost same morphological and microscopical characters like prismatic crystals, starch grains etc. Hence it is concluded that D. laxiflorum may be considered as a substitute for D. gangeticum on the basis of present pharmacognostical study.

Diuretic activity of Linaria ramosissima (wall.) Janch. leaves in albino rats.

Linaria ramosissima (Wall.) Janch., Scrophulariaceae, a folklore plant, has been claimed for its diuretic activities by traditional practitioners. The present study was undertaken to investigate the diuretic activity of L. ramosissima leaves in albino rats. Suspension of leaf powder in 2% gum acacia was administered to experimental rats orally at doses of 450 mg/kg. The diuretic effect was evaluated by measuring the urine volume, pH of urine, and urinary electrolyte excretion. Administration of the test drug increased the urine volume in a non-significant manner, while it enhanced the urinary excretion of sodium, chloride, and potassium significantly, in comparison to the control group. From the present study it can be concluded that the leaves of L. ramosissima have a significant diuretic activity.

Pharmacognostical and analytical study of Tulsi-Amla-Yasti Ghrita.

Tulasi Amla Yashti Ghrita is an Ayurvedic formulation, which is beneficial in the management of the side effects of Head and Neck Malignancies induced by Radiotherapy and Chemotherapy. A pharmacognostical study involving both the macroscopic and powder microscopy of raw drugs of Tulasi Amla Yashti Ghrita and a physicochemical analysis of the finished product were carried out, to evaluate the quality of the formulation. The specific gravity of the formulation was 0.9130 and pH was 3.5. Thin layer chromatography (TLC) and high performance thin layer chromatography (HPTLC) were carried out after organizing the appropriate solvent system, in which five spots were distinguished in TLC and nine spots in HPTLC. Most of the Rf values for the spots observed were identical. The observations could be considered to be the reference standards in future studies.