clay and Diarrhea

Calcium aluminosilicate clay (CASAD) is a naturally occurring clay that serves as a cation exchange absorbent. We hypothesized that oral administration of CASAD would reduce the rate of grade 3/4 diarrhea associated with irinotecan use for metastatic colorectal cancer (CRC) by adsorbing the SN-38 metabolite.. Patients receiving irinotecan-based chemotherapy were randomized equally between CASAD and placebo arms in this multicenter trial in order to assess differences in the proportions of patients with grade 3/4 diarrhea within 6 weeks. Additionally, we compared symptom severity between the two arms using the M.D. Anderson Symptom Inventory.. Between May 2009 and May 2012, 100 patients were enrolled. In evaluable patients, 7 of 43 (16 %) on the CASAD arm compared to 3 of 32 (9 %) on the placebo arm experienced grade 3/4 diarrhea (P = 0.70). The rate of any diarrhea among all patients was similar (CASAD arm, 64 % vs. placebo arm, 70 %). The rate of study dropout was 14 % in the CASAD arm and 38 % in the placebo arm (P = 0.01). No differences were found in symptom severity, individual symptom items, and in serious adverse events between the two arms.. Compared to placebo, CASAD use was safe but ineffective in preventing diarrhea in metastatic CRC patients treated with irinotecan-containing chemotherapy regimens. There were no distinct signals in terms of patient symptoms between arms, but there was significantly more patient dropout in the placebo arm. Future CASAD trials will focus on the active treatment of diarrhea.

Topics: Adult; Aged; Aged, 80 and over; Aluminum Silicates; Antineoplastic Agents, Phytogenic; Camptothecin; Clay; Colorectal Neoplasms; Diarrhea; Double-Blind Method; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Placebos; Treatment Outcome; Young Adult

Two experiments were conducted to determine whether 3 different clays in the nursery diet reduce diarrhea of weaned pigs experimentally infected with a pathogenic Escherichia coli. Weaned pigs (21 d old) were housed in individual pens of disease containment chambers for 16 d [4 d before and 12 d after the first challenge (d 0)]. The treatments were in a factorial arrangement: 1) with or without an E. coli challenge (F-18 E. coli strain; heat-labile, heat-stable, and Shiga-like toxins; 10(10) cfu/3 mL oral dose daily for 3 d from d 0) and 2) dietary treatments. The ADG, ADFI, and G:F were measured for each interval (d 0 to 6, 6 to 12, and 0 to 12). Diarrhea score (DS; 1 = normal; 5 = watery diarrhea) was recorded for each pig daily. Feces were collected on d 0, 3, 6, 9, and 12 and plated on blood agar to differentiate β-hemolytic coliforms (HC) from total coliforms (TC) and on MacConkey agar to verify E. coli. Their populations on blood agar were assessed visually using a score (0 = no growth; 8 = very heavy bacterial growth) and expressed as a ratio of HC to TC scores (RHT). Blood was collected on d 0, 6, and 12 to measure total and differential white blood cell (WBC) counts, packed cell volume (PCV), and total protein (TP). In Exp. 1 (8 treatments; 6 replicates), 48 pigs (6.9 ± 1.0 kg of BW) and 4 diets [a nursery control diet (CON), CON + 0.3% smectite (SM), CON + 0.6% SM, and CON until d 0 and then CON + 0.3% SM] were used. The SM treatments did not affect growth rate of the pigs for the overall period. In the E. coli challenged group, the SM treatments reduced DS for the overall period (1.77 vs. 2.01; P < 0.05) and RHT on d 6 (0.60 vs. 0.87; P < 0.05) and d 9 (0.14 vs. 0.28; P = 0.083), and altered differential WBC on d 6 (neutrophils, 48 vs. 39%, P = 0.092; lymphocytes, 49 vs. 58%, P = 0.082) compared with the CON treatment. In Exp. 2 (16 treatments; 8 replicates), 128 pigs (6.7 ± 0.8 kg of BW) and 8 diets [CON and 7 clay treatments (CON + 0.3% SM, kaolinite, and zeolite individually and all possible combinations to total 0.3% of the diet)] were used. The clay treatments did not affect growth rate of the pigs. In the E. coli challenged group, the clay treatments reduced DS for the overall period (1.63 vs. 3.00; P < 0.05), RHT on d 9 (0.32 vs. 0.76; P < 0.05) and d 12 (0.13 vs. 0.39; P = 0.094), and total WBC on d 6 (15.2 vs. 17.7 × 10(3)/μL; P = 0.069) compared with the control treatment. In conclusion, dietary clays alleviated diarrhea of weaned pig

Topics: Aluminum Silicates; Animal Feed; Animal Husbandry; Animals; Clay; Diarrhea; Diet; Escherichia coli; Escherichia coli Infections; Feces; Female; Male; Swine; Swine Diseases; Weaning

SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents pathogenic effects by binding the virus and its enterotoxin. We tested the trapping and anti-inflammatory properties of diosmectite in a SARS-CoV-2 model. Trapping effects were tested in Caco-2 cells using spike protein receptor-binding domain (RBD) and heat-inactivated SARS-CoV-2 preparations. Trapping was assessed by immunofluorescence, alone or in the presence of cells. The effect of diosmectite on nuclear factor kappa B (NF-kappaB) activation and CXCL10 secretion induced by the spike protein RBD and heat-inactivated SARS-CoV-2 were analyzed by Western blot and ELISA, respectively. Diosmectite bound the spike protein RBD and SARS-CoV-2 preparation, and inhibited interaction of the spike protein RBD with ACE2 receptors on the Caco-2 cell surface. Diosmectite exposure also inhibited NF-kappaB activation and CXCL10 secretion. These data provide direct evidence that diosmectite can bind SARS-CoV-2 components and inhibit downstream inflammation, supporting a mechanistic rationale for consideration of diosmectite as a management option for COVID-19-associated diarrhea.

Topics: Adsorption; Aluminum Compounds; Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Binding Sites; Caco-2 Cells; Chemokine CXCL10; Chromatography, Liquid; Clay; COVID-19 Drug Treatment; Diarrhea; Enterocytes; Gastroenterology; Humans; Magnesium Compounds; Mass Spectrometry; Molecular Docking Simulation; Molecular Dynamics Simulation; NF-kappa B p50 Subunit; Protein Binding; Protein Domains; Rotavirus; SARS-CoV-2; Silicates

Medullary thyroid cancer (MTC)-related diarrhea can be debilitating, reduces quality of life (QOL), and may be the only indication for initiating systemic therapy. Conventional antidiarrheal drugs are not always helpful and may have side effects. Calcium aluminosilicate antidiarrheal (CASAD), a natural calcium montmorrilonite clay, safely adsorbs toxins and inflammatory proteins associated with diarrhea. It was hypothesized that CASAD would reduce the severity of diarrhea and improve QOL in MTC patients.. This was a prospective pilot trial (NCT01739634) of MTC patients not on systemic therapy with self-reported diarrhea of three or more bowel movements (BMs) per day for a week or more. The study design included a one-week run-in period followed by one week of CASAD ± a two-week optional continuation period. The primary endpoint was efficacy of one week of CASAD treatment in decreasing the number of BMs per day by ≥20% when compared with the baseline run-in period. Secondary objectives included tolerability and safety and the impact on QOL using the MD Anderson Symptom Inventory-Thyroid questionnaire (MDASI-THY).. Ten MTC patients (median age = 52 years, 70% female, 80% white) were enrolled. All had distant metastases, and median calcitonin was 5088 ng/mL (range 1817-42,007 ng/mL). Ninety percent had received prior antidiarrheals, and 40% of these had used two or more drugs, including tincture of opium (30%), loperamide (50%), diphenoxylate/atropine (20%), colestipol (10%), or cholestyramine (10%). Of seven evaluable patients, four (56%) had ≥20% reduction in BMs per day. Six out of seven patients discontinued their prior antidiarrheals. Best response ranged from 7% to 99% reduction in mean BMs/day from baseline. Five out of seven patients considered CASAD a success, and they opted for the two-week continuation period. Improvements in diarrhea and all six interference items assessed by MDASI-THY were noted at weeks 1 and 3. Total interference score was significantly improved at three weeks compared with baseline (p = 0.05). An oral levothyroxine absorption test was performed in one patient; malabsorption of levothyroxine was not observed. Adverse events included flatulence (40%), bloating (10%), heartburn (10%), and constipation (10%).. CASAD is a promising strategy for treatment of MTC-related diarrhea. In this small pilot study, improvements in frequency and quality of diarrhea as well as QOL were noted. Further studies in this population are warranted.

Topics: Adult; Aged; Aluminum Silicates; Antidiarrheals; Carcinoma, Medullary; Clay; Diarrhea; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Quality of Life; Thyroid Neoplasms; Treatment Outcome