Clostridium Difficile Infection

This Phase 1 study is designed to assess the safety, tolerability, and pharmacokinetics of single and multiple intravenous doses of BWC0977 when administered to healthy adult volunteers. This is a randomized double-blind, placebo-controlled, ascending dose, multi-cohort trial. A total of 64 healthy volunteers are expected to be enrolled in 8 Cohorts. The study will be conducted in two phases: A single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants in Cohorts 1 - 2 will receive one dose of BWC0977 or placebo. In MAD, participants in cohorts 3 - 7 will receive multiple doses of BWC0977 or placebo for 7-10 consecutive days (as per the schedule). In both parts, sequential cohorts will be exposed to increasing doses of BWC0977.

The purpose of this study is to find out whether SER-155 may be a safe first treatment that causes few or mild side effects for people due to irEC.

In this study the stool of patients who are being treated for COVID-19 will be tested during treatment and then again following treatment to determine if the virus is shed in the stool during infection, afterwards, or both.

This is a single center, randomized, exploratory clinical investigation that will evaluate the safety and efficacy of Toxclean (ABResearch srl) as add on treatment to Standard therapy in 24 patients with recurrent CDAD. Eligible subjects will be adult patients with recurrent CDAD. Recurrent CDAD, for the purpose of this protocol, is defined as one or more new episode of diarrhea (Ned) within two months from the end of the SoC treatment. The objective of this pilot study is to evaluate whether 1 or 2 grams of Toxclean powder is orally administrable and well tolerated as add on treatment to SoC in patients with recurrent CDAD. Primary * Percentage of patients that complete Toxclean schedule treatment; Secondary * Safety and tolerability of two different dosage of oral Toxclean treatment; * Reduction of toxin amount in fecal sample; * Clinical response after 28-day oral administration of two different dosage of TOXCLEAN in combination with SoC therapy; * CDAD symptoms improvements during treatment and follow up periods; * Fecal concentration of Toxclean;

This is a Phase II randomized, placebo-controlled, double-blinded, dose-ranging study to determine optimal effective dose and safety of AQ between 0, 4, 24, and 44 g doses administered orally for ten days concurrent with standard treatment (oral vancomycin or fidaxomicin at UVa) among cases of CDI in hospitalized persons, persons who are referred to the UVA C. difficile clinic or Carilion Hospital, age 18 and older. The investigators hypothesis is that AQ will reduce recurrence (primary outcome) and mortality (secondary outcome) at 60 days post-treatment. Furthermore, the investigators hypothesize that alanyl-glutamine supplementation will be associated with decreased intestinal and systemic inflammation and improvement of intestinal microbial and metabolic profiles. The investigators plan to enroll 260 patients, equally divided into 4 arms. Upon enrollment, participants will be randomized to either receive AQ at 4, 24, or 44 g or placebo (water). Study agent is administered once a day, orally or enterally, if feeding tube is present. Because the investigators are enrolling subjects over a longer period of time, block randomization will be used to ensure that relative temporal balance is maintained throughout the trial. Participants will be followed up daily during treatment for adverse event monitoring and weekly for 60 days post-treatment for recurrences and survival. Blood, urine and stool specimens will be collected at days 0, 10 and 70 to assay for markers of inflammation and microbial and metabolic profiling. For those not able to, or who refuse in-person visits, the investigators will allow a virtual encounter and shipment of the study agent. If not able to come for in person visits, blood draws may be omitted and shipment of urine and stool specimens will be allowed. Sample collection containers will also be provided as needed for sample transport to the participants next scheduled follow-up visit. The data set utilized for all initial baseline feature and demographic reporting will be the Intention to Treat Analysis Dataset, which will be comprised of all randomized participants. The primary dataset will be a Modified Intention to Treat Analysis Dataset for all endpoints, comprised of all participants who took at least one dose of study intervention (placebo or treatment), regardless of completeness of follow-up outcome data. The Safety Analysis Dataset will be all participants who took at least one dose of study intervention. The Per Protocol Analysis Dataset will be those patients who took at least 9 doses of study intervention for 9 days of the treatment period (10 days). Analysis will utilize ANOVA unless statistically significant differences in the distribution of baseline characteristics or features of non-normality are detected and relevant, at which point contingency utilization of ANCOVA, logistic regression, or other approaches as appropriate will be implemented. Treatment group level rates will be presented as incidence risk ratios relative to the control (placebo) group with 95% confidence intervals. Safety endpoints will be evaluated on an individual AE by AE event via the DSMB and utilizing summary statistics during treatment and through duration of follow up. Adverse events will be presented by System Organ Class and will include information on start and stop date, severity, projected relationship, expectedness, and outcome and duration (the latter two after the event is considered to have concluded).

This is a prospective, open-label, single-arm clinical study designed to evaluate changes in gut and digestive health parameters following daily use of a dietary supplement system over an eight-week period. Gut and digestive health are essential to overall human health and are closely associated with immune regulation, nutrient absorption, metabolic function, and systemic inflammation. The gastrointestinal tract contains a complex microbial ecosystem that supports digestion, produces bioactive metabolites, and modulates immune responses. Disruptions in gut microbiota composition, intestinal barrier integrity, and immune balance have been associated with digestive symptoms, inflammation, and reduced well-being. This study will enroll approximately 50 adult male and female subjects between 18 and 80 years of age who meet all inclusion and exclusion criteria, including self-reported gastrointestinal symptoms as assessed by the Gastrointestinal Symptom Rating Scale (GSRS). All participants will consume the study product daily for a total of eight weeks while maintaining their usual diet and lifestyle habits, as outlined in the protocol. The dietary supplement system consists of two study products that contain a combination of plant-derived nutrients, fibers, probiotics, digestive enzymes, and antioxidant-rich botanical ingredients. These components are intended to support gut microbial diversity, digestive processes, immune balance, and intestinal barrier integrity. Objective assessments of gut and digestive health will be conducted using stool-based laboratory evaluations at baseline and at the end of the study. These assessments include biomarkers related to microbial diversity, inflammation and immune activity (such as calprotectin, beta-defensin 2, and secretory IgA), digestive health markers (including short-chain fatty acids, bile acids, and malabsorption markers), and markers associated with intestinal barrier integrity and permeability. Participant-reported outcomes will be collected using validated questionnaires, including the Gastrointestinal Symptom Rating Scale (GSRS) and a Subjective Digestive Health and Well-Being Questionnaire. These assessments will be administered at baseline and at regular intervals throughout the study to evaluate changes in gastrointestinal symptoms, digestive comfort, overall well-being, and product tolerability. Safety assessments will be conducted throughout the study period, including monitoring of adverse events, concomitant medications, and study product compliance. The overall safety and tolerability of the dietary supplement system will be evaluated based on reported adverse events and clinical assessments.

This Phase 1 pilot clinical trial that will evaluate the initial safety and feasibility of orally administered preparation of fecal microbiota (MTP-101P) in patients undergoing colon resection. We plan to enroll male and female patients, ages 18-75, diagnosed with colon polyps or early (stage I or II) colorectal cancer or medically refractory diverticulitis. We will recruit 40 patients total to receive the investigational product. This trial will inform development of future trials in treatment of colon and rectal surgery. Active drug is composed of highly purified, freeze-dried, fecal microbiota from healthy donors. This study will also allow for limited evaluation of pharmacokinetics in terms of donor microbiota engraftment. The exploratory objective is to evaluate engraftment of donor microbiota with this preparation and compare the results with data generated with the data generally from microbiota transplantation (IND28152). Stool samples may be returned via mail rather than clinic visit.

PRIMARY OBJECTIVE: I. To compare novel, home-based methods of quantitating medication concentrations in either saliva or sweat to the 'gold standard' of liquid chromatography - mass spectrometry of plasma. SECONDARY OBJECTIVES: I. To compare novel home-based methods of quantitating substances in either saliva or sweat to the 'gold standard' in plasma. II. Assess the ease of obtaining home-based samples. OUTLINE: Patients undergo collection of sweat samples via Macroduct Sweat Collection System 3710S and saliva and blood samples within 24 hours after medication administrations. Patients also complete questionnaires over 5-10 minutes and have medical charts reviewed. After completion of study, patients are followed up periodically.

Hospitals and clinics interested in participating in this multi-site study, please contact the people mentioned under "Contacts and Locations". This prospective observational study will enrol 60 otherwise healthy adults with a documented history of first recurrent Clostridioides difficile infection (rCDI). Eligible participants must have had a confirmed positive toxin B test for C. difficile, with the initial infection occurring within the past 12 months. At the time of enrolment (Day 0), participants must have completed a standard-of-care oral antibiotic therapy for their first rCDI no more than five days prior and be asymptomatic for CDI. Potential participants will sign an informed consent form at their initial visit to their doctor (visit 1) and provide a stool sample for c diff testing. Participants will only be considered 'enrolled' if their stool sample is positive for toxin B and they meet all other criteria at visit 2 (week 0). The primary objective of the study is to measure the rate of CDI recurrence within an 8-week follow-up period. The secondary objective is to assess stool levels of Toxin A and B at baseline, week 2, and week 8. The second objective will enable exploration of the reliability of using high-sensitivity assays for toxin detection in stool. Further, potential correlations between post-treatment stool toxin levels and rCDI development will be explored.

Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea, and the most common health care-associated infectious disease in the United States, accounting for 15% of overall infections, nearly 30.000 deaths per year an estimated economic expense of $5 billion/year. In the last decade, most of the burden related to CDI depends on recurrence CDI (rCDI) (3). rCDI is known to extend the hospitalization length, and to be associated with increased morbidity and mortality rates. Furthermore, rCDI is often, more than primary infection, associated with life-threatening complications, including pseudomembranous colitis, toxic megacolon, shock, perforation, bloodstream infection (BSI), sepsis, caused by intestinal bacteria or fungi with a mortality rate nearly 50%, and death. Fecal microbiota transplantation (FMT), defined as the infusion of feces from healthy donors to recipient with disorders associated to dysbiosis, is known to be a highly effective treatment option against CDI. FMT is also more effective than standard treatment with vancomycin and it is recommended by International Guidelines for treating multiple recurrence of CDI. Despite the increasing body of evidence about the clinical efficacy of FMT for the treatment of rCDI, mechanisms for this clinical efficacy are also unknown. Metagenomics analysis is known as a good option to examine gut microbiota and to estimate microbial diversity. The aim of this study is to evaluate changes in microbial composition in rCDI patients after FMT, using metagenomics analysis. The investigators will carry out a single-center observational perspective study. Patients will be recruited among those referred to the gastroenterology unit of the Fondazione Policlinico Universitario "A. Gemelli". Patients with all inclusion criteria and none of the exclusion criteria (detailed in the specific section of this website) will be considered for this study. Before FMT procedure, demographic data will be collected by the gastrointestinal disease staff. Moreover, patients will be requested to give stool samples to be collected in a sterile, sealed container and stored at -80°C for metagenomic assessment of gut microbiome and meta-transcriptome assessment by the microbiology staff. Patients, according to clinical practice, will receive FMT procedure by colonoscopy. Each patient of the study will receive faeces from one single donor without any specific recipient-donor match. The selection of stool donors will be performed by the gastroenterology unit staff following protocols previously recommended by international guidelines and according the new recommendation imposed by the reorganisation of faecal microbiota transplant during the COVID-19 pandemic. All faecal infusates will be manufactured in the microbiology unit of our hospital. Only frozen faeces will be used. Preparation of frozen faeces will follow protocols from international guidelines. Follow-up visits will be performed by physicians from the gastroenterology unit. All patients will be followed up for 3 months after the end of treatments. Follow-up visits will be scheduled at week 1, week 2, week 4, and week 12, after the end of treatments. At each visit investigators will collect stool samples for microbiome analysis. Study Outcomes are detailed in the specific section of this website. For microbiome analysis, statistical differences between group means will be calculated using a two-tailed Wilcoxon-Rank Sum Test, through the R statistical software package (R Core Team, Vienna, Austria).