Clinical Research Directory

FMT for Lung and Associated-organ Rescue Efficacy in ARDS Patients

Acute respiratory distress syndrome (ARDS) represents a substantial global health burden. In the intensive care unit (ICU), the concurrent administration of antibiotics, opioids, proton pump inhibitors (PPIs), vasoconstrictors, and parenteral nutrition-compounded by the intrinsic severity of critical illness-induces profound gut microbiota dysbiosis. Accumulating preclinical and clinical evidence indicates that such intestinal dysregulation may trigger distal immunomodulatory and microbial shifts in the lung via the gut-lung axis, thereby contributing to pulmonary microecological imbalance and impairing recovery trajectories. Although pulmonary microecology has garnered increasing scientific attention, the causal and temporal relationship between gut dysbiosis and the establishment or exacerbation of pulmonary microbial dysbiosis in ARDS remains inadequately characterized. As a result, it is currently unclear whether gut dysbiosis serves as a primary pathogenic driver, a disease-amplifying factor, or a secondary epiphenomenon in the context of ARDS-associated lung injury. Fecal microbiota transplantation (FMT) is a targeted microbiome-modulating intervention that involves the transfer of functionally diverse, minimally processed microbial communities from comprehensively screened healthy donors to restore ecological stability and functional redundancy in the recipient gut. Robust clinical data demonstrate that FMT effectively decolonizes the gastrointestinal tract of multidrug-resistant organisms (MDROs) and reduces the incidence of secondary infections in immunocompetent, non-critically ill populations. Over the past decade, FMT has demonstrated reproducible efficacy in recurrent Clostridioides difficile infection and emerging promise in select extra-intestinal inflammatory conditions-highlighting its capacity as a mechanism-informed strategy for systemic host-microbe recalibration. Given the established role of the gut as a reservoir for enteric pathogens implicated in sepsis, hospital-acquired bloodstream infections, and ventilator-associated pneumonia (VAP), we propose a prospective, single-center, open-Label, randomized controlled trial (RCT) enrolling mechanically ventilated adults with ARDS. The primary objective is to evaluate whether adjunctive FMT-delivered via nasojejunal tube-decrease 28-day mortality.

Oral Lactobacillus Reuteri for Skin Barrier Dysfunction in Obesity

This clinical trial aims to evaluate the safety and efficacy of oral Lactobacillus reuteri supplementation for treating obesity-induced skin barrier impairment in individuals aged 18-40 with a BMI ≥30. The study focuses on the following questions: Can oral Lactobacillus reuteri supplementation reduce skin barrier damage (measured by transepidermal water loss/TEWL) in obese participants? Does modulation of gut microbiota with Lactobacillus reuteri impact skin barrier function and systemic inflammation? Researchers will compare outcomes across two groups: Intervention Group (Obese): Oral Lactobacillus reuteri capsules. Placebo Control Group (Obese): Oral inactive (heat-killed) Lactobacillus reuteri. Participant Procedures: Take daily oral capsules (Lactobacillus reuteri or inactive strain) for 4 weeks. Undergo non-invasive skin testing (TEWL measurements) at baseline and study completion. Provide stool and samples for analyses. Complete weekly check-ins to report adverse effects (e.g., gastrointestinal discomfort, skin irritation).

Synbiotics in Patients at RIsk fOr Preterm Birth

Prematurity remains the main cause of death and serious health problems in new-borns. Besides the need for hospitalization and medical interventions in the first weeks or months of the new-borns' life, prematurity can cause long-lasting health problems (e.g. multiple hospital admissions, developmental delay, learning difficulties, motor delay, hearing or eye problems, ...). Moreover, prematurity places an enormous economic burden on the society. Aside from the medical problems and the financial cost, the emotional stress and psychological impact on the parents, siblings and other family members should not be underestimated. Previous preterm delivery (before 37 weeks of pregnancy) increases the risk for recurrent preterm delivery in a subsequent pregnancy. Therefore, these women should be considered as 'high risk' for preterm birth. Infections ascending from the vagina may be an important cause of preterm delivery in certain cases. Some women have an abnormal vaginal microbiome and are therefore at risk for infections and preterm birth. On the other hand, the vaginal flora is more stable and resistant to infections in healthy pregnant women who deliver at term (after 37 weeks of gestation). Synbiotics are a mixture containing probiotics and prebiotics. Probiotics are living bacteria with potential beneficial effects that can be used safely in pregnancy, while prebiotics are consumed by the bacteria. It is known that probiotics, when used for a long period of time, can maintain a healthy and stable vaginal flora that may protect against infections. In this study, pregnant patients with a history of preterm birth will be included in the first trimester of pregnancy to start with synbiotics or placebo. The investigators will examine the effect of synbiotics on the vaginal flora and on the pregnancy duration. The hypothesis is that synbiotics, when started early in the pregnancy, can change the disturbed vaginal flora into a stable micro-environment.

Changes in Bile Acids and Microbiota in Patients With Hepatitis D Treated With Bulvertide

HDV is an RNA virus that infects only in the presence of HBV, affecting about 13% of HBsAg carriers. In Italy, prevalence ranges from 3.2% to 9.3%. It increases the risk of cirrhosis, fulminant hepatitis, and HCC, particularly in high-risk groups (HIV, HCV, drug users, dialysis patients). Until 2020, pegIFN was the only therapy; since 2022, bulevirtide (BLV) has been available, blocking viral entry into hepatocytes and reducing HDV RNA and liver stiffness, with efficacy in 45-48% of patients, though the optimal treatment duration remains uncertain. The gut microbiota and bile acids also play a role in fibrosis and cirrhosis progression: dysbiosis, typical in cirrhotic patients, alters bile acid metabolism and increases intrahepatic toxicity.

DOnor Milk to REpair the Full-term Infant MIcrobiome in Infants Born Via Cesarean Section.

The objective of this novel study is to establish proof of concept using a pilot randomized controlled trial to determine the effect of DHM compared to formula supplementation on the microbiome in full-term infants who are born via caesarean section and require supplementation. Secondarily, this study aims to compare the infant health outcomes of sleep and growth between groups to assess if these outcomes are mediated by infant feeding type or potential differences in microbial signatures. Finally, this study will compare maternal outcomes of depression, anger, breastfeeding self-efficacy and breastfeeding rates between groups. The infant gut microbiome plays a critical role in the developing immune, neurologic, and endocrine systems. Yet, most infants experience early life disruptions (ELDs) to their microbiome that have potential long-term health and development impacts. A major source of disruption is caesarean section (c-section) delivery because the infant is born surgically and is not exposed to important commensal bacteria required to establish the infant microbiome. Currently in Canada, over 28% of infants are born via c-section. Exclusive breastfeeding can improve gut microbiota composition in infants who are born via c-section. However, approximately 60% of infants born via c-section require formula supplementation in their first week of life. Evidence indicates that even one bottle of formula can further disrupt the gut microbiome. Donor human milk (DHM) is a superior alternative to formula when supplementation is required as its biotic properties minimize perturbations to the infant gut microbiome and may help to repair the microbiome in infants who experience ELDs. Yet, while DHM is well researched in preterm populations, evidence on the impact of DHM as a therapeutic intervention on the full-term infant gut microbiome is lacking. The hypothesis of this study is: that replacing formula with DHM supplementation will minimize gut microbiome dysbiosis and foster homeostasis following supplementation. In addition, it is hypothesized that improved homeostasis will promote improved sleep and growth outcomes in participant infants. Finally, mothers whose infants receive DHM will have lower depression and anger scores and higher breastfeeding self-efficacy and exclusive breastfeeding rates compared to mothers whose infants receive formula.

Assessment of the Ocular Microbiome in Health and Disease

The objective of this application is to illustrate the core constituents of the ocular surface microbiome, describe factors that promote colonization, and assess the ocular microbiome's role in the health of the anterior segment. We will conduct a prospective, observational cohort study, including a longitudinal analysis of the ocular microbiome in adults.

Effects of Pulse Consumption, Gut Microbiome, and Appetite in Healthy Participants

The purpose of the study is to investigate the effects of pulse consumption versus no pulse consumption on the gut microbiome, meal satiety, and short-chain fatty acid metabolomics.

Micronutrient and Additive Modifications May Optimize Diet To Health

This is a prospective clinical intervention trial where patients with moderately active ulcerative colitis are randomized to either normal healthy diet or a diet with elimination of emulsifying agents within the E 400-group with special respect to carragenan, CMC and polysorbates. At study start and end after one month their diet, clinical characteristics and microbiota will be analysed. The hypotheses are that their disease activity measured with calprotectin and their microbiota will improve after intervention.

Effects of Mouthrinse on the Microbiome of the Oral Cavity and GI Tract

The purpose of this research study is to identify the effects of 2 over-the-counter mouthwashes on bacteria and 3 viruses in the participant's mouth and gut. The participant will be randomly allocated to rinse their mouth twice daily either with Listerine mouthwash, Lumineux Oral Essentials mouthwash, or water. The overall duration of the study will be approximately 180 days and will include approximately 5 visits and 15-30 minutes for each visit with a total of approximately 2.5 hours of your time. Additionally, fecal matter will also be collected in some subjects using a commercial collection kit.

Frequent Standardized Oral Care to Improve Health Outcomes in Premature Infants in the Neonatal Intensive Care Unit

Premature very low birth weight (VLBW) infants are susceptible to complications related to infrequent and non-standardized oral care. Although the benefits of frequent standardized oral care are known to reduce oral dybiosis (increased level of potentially pathogenic bacteria) and its associated complications in critically ill adults leading to established evidence-based guidelines, no such information exists for VLBW infants. The proposed study will prospectively follow 40 VLBW infants for 4 weeks following birth. Infants will be randomized into 1 of 2 groups. Standardized oral care will be performed every 3-4 hours (Group 1) and every 12 hours (Group 2). Aim 1 will evaluate the feasibility of frequent standardized oral care, Aim 2 will compare the oral microbiome between groups, and Aim 3 will compare respiratory outcomes including the incidence of ventilator associated pneumonia, bronchopulmonary dysplasia and need for respiratory support between infants receiving standardized oral care every 3-4 hours and every 12 hours. Issues related to recruitment, retention, randomization, acceptance by nursing staff, and treatment fidelity will be examined. Saliva samples will be obtained weekly and analyzed using 16S sequencing, respiratory cultures will be obtained weekly on ventilated infants, and respiratory outcomes will be collected from the medical records.

Feasibility and Safety Study of Parent-to-Child Nasal Microbiota Transplant

This feasibility and safety pilot study looks to determine whether transferring a parents healthy, diverse nasal microbiota to the participant's infant(s) will create a healthy, diverse neonatal nasal microbiome.

An Examination of Infants' Microbiome, Nutrition, and Development Study.

This study is examining the relationship between infant nutrition, gut health, and development. The fecal microbiota changes and develops, in large part due to the food that infants eat. These changes are important for many aspects of development. This study is designed to examine how the fecal microbiota changes when exclusively breastfed infants are first introduced to solid food, and how changes of the fecal microbiota are related to other aspects of development.

Early Protein Supplementation in Extremely Preterm Infants Fed Human Milk

The central hypothesis of this clinical trial is that, in extremely preterm infants, protein-enriched human milk diets compared to usual human milk diets during the first 2 weeks after birth increase fat-free mass (FFM)-for-age Z scores and promote maturation of the gut microbiome at term corrected age.

NICU Antibiotics and Outcomes Trial

The goal of the NANO trial is to study the longstanding clinical practice of empirically administering intravenous antibiotics to extremely low birthweight (ELBW) infants in the first days of life. In this 802-subject multicenter placebo-controlled randomized clinical trial, the hypothesis to be tested is that the incidence of adverse outcomes is higher in babies receiving empiric antibiotics (EA) in the first week of life compared to babies receiving placebo. The study targets a population of ELBW infants in whom the clinical decision to use or not use EA is currently most challenging -- infants that are clinically stable that did not have a known exposure to intraamniotic infection and were not born preterm for maternal indications. The primary outcome is the composite outcome of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death during the index hospitalization. Secondary safety outcomes will include total antibiotic days, days to full enteral feedings, and common morbidities in preterm infants that have previously been linked to EA, e.g. retinopathy of prematurity and bronchopulmonary dysplasia. Weight and length z-score, and head circumference, are standard measures to be collected weekly by clinical team per a standardized protocol.

Comparing Single Versus Repeat NMT on the Diversity of the Neonatal Nasal Microbiome

This study aims to determine whether a parent-to-child nasal microbiota transplant (NMT) can seed and engraft parental organisms into the neonatal microbiome and increase the neonatal microbiome diversity.

Administering NMT to Reestablish Infant Nasal Microbiome Diversity Following Intranasal Mupirocin Treatment

This protocol aims to evaluate how NMT affects pediatric nasal microbiome diversity following intranasal mupirocin treatment

Pilot Haskap Metabolite Timing Project

Diet is a key factor in managing health and individuals at risk of developing metabolic syndrome or other chronic diseases have the opportunity to use diet as a tool to improve their health. This can be complicated when considering the numerous variables that impact digestion and absorption of key health-promoting compounds in foods. One of these variables is the gut microbiome, a microbial community in the digestive tract that interacts with the foods we consume. The mechanisms the microbiome uses to interact with bioactive compounds in foods, like polyphenols, can modulate the health-promoting benefits of polyphenols. Polyphenols are secondary plant metabolites, commonly found in fruit, legumes, chocolate, coffee, and nuts among other foods that have been shown to improve cardiovascular and metabolic health, as well as reduce inflammation and oxidative stress.

Understanding the Burn Wound Microbiome: Comparing Traditional Wound Cultures to Next Generation Sequencing Technology

The purpose of this investigation is to better understand the wound microbiome in burn wounds and the role it plays in outcomes and complications related to treatment.

Minimal Flow Anesthesia and Infection Risk

This study is being done to find out if the heat and moisture that build up during minimal flow anesthesia can lead to the growth of germs (microorganisms) inside the anesthesia equipment. Minimal flow anesthesia (using fresh gas flow of 0.5 liters per minute or less) is known to help protect the lungs and the environment. However, it may also cause water to collect in the equipment, which could allow germs to grow. In this study, we want to see whether this type of anesthesia is safe when it comes to the risk of germs in the equipment.

Effect of Crown Material on Gingival Microbial Colonization

* Prior approval from SOD ethical committee has been received. * All patients presenting to the General OPD of School of Dentistry, Islamabad will be screened. Those patients who fulfill the criteria will be referred to the Prosthodontics department. * The patients will undergo detailed history and oral examination after informed consent (Annexure-A). Patients will undergo radiographic investigation and based on this information they will be selected for the study according to the exclusion and inclusion criteria. * Eligible participants will be randomly assigned to one of the following groups using a computer-generated sequence with allocation concealment via sealed opaque envelopes: * Group A: Control group * Group B: Full-coverage PFM crowns * Group C: Full-coverage Zirconia crowns * Baseline gingival samples will be collected with the help of sterile swab from the target tooth region prior to prosthesis placement and at the follow-up visits i.e. 1, and 3 months; both for experimental groups and control group. * Microbial analysis will be conducted through culture techniques to quantify CFUs and identify species. * A summary of the micro-organisms, their incubation media, temperature and time is presented in the following table: Table 1: Summary of the micro-organisms, their incubation media, temperature and time Micro-organism Growth Media Temperature Incubation time Candida albicans Saboraud Agar 370C 24-48 hours Streptococcus mutans BHI broth 370C 24-48 hours Staphylococcus aureus BHI broth 370C 24-48 hours Porphyromonas gingivalis BHI broth 370C 18-24 hours * Alongside, the same sample from sterile swabs will be smeared by fixating it on a microscopic slide and then Candida albicans will be stained by Periodic Acid Schiff technique, and the bacterial species using Gram staining. * All participants will receive standardized verbal and written instructions oral hygiene instructions to control for hygiene-related variation

The Effect of Smoking on Peri-implantitis

the primary aim of this project is to evaluate the microbiological and inflammatory effect of smoking status and smoking severity on periimplantitis lesions. The secondary aim is to compare the effect of smoking on periimplantitis and periodontal microbiota and inflammation in the same individuals. There will include 96 patients, equally divided into four groups: Smokers with peri-implantitis (n=24), non-smoker individuals with peri-implantitis (n=24), smokers with healthy peri-implant tissues (n=24), non-smoker individuals with healthy peri-implant tissues (n=24). Microbiological and biochemical analyses will be performed on the samples taken.

Changes in Microbial Status From Dentate, Edentulous and After Dental Implant Placement

The objectives of this study are to analyze the oral microbiome modulations occurring during the transition from partial (with some residual teeth) to full edentulous (without remaining teeth) status and implant placement in subjects affected by severe periodontitis; to evaluate if microbiome changes in relation to the used of different implant material/surface; and to assess the variance of the changes to determine the sample size for future longitudinal prospective studies.

Skin Preparation for Elective Foot and Ankle Surgery

Surgical site infections (SSIs) make about 31% of all nosocomial infections and they are the most common hospital-acquired infection. For foot and ankle elective interventions, SSI rate is reported between 0.4% and 3.6%. This study will investigate the effectiveness of skin cleaning with isopropyl alcohol and scrubbing with chlorhexidine soap before standard skin preparation in reducing microbial load and surgical site infections for elective foot and ankle surgeries. Current standard of care includes skin preparation with iodine or chlorhexidine solution prior to sterile draping and the start of surgery. Standard of care will be applied to all patients. The use of an additional "pre-scrub" with isopropyl alcohol and scrubbing with chlorhexidine soap will be applied to the experimental group. The control group will receive only the standard of care skin preparation with iodine or chlorhexidine solution prior to draping.

Personalized Responses to Dietary Composition Trial 3

The PREDICT 3 study will build on previous research in over 2,000 individuals to further refine machine learning models that predict individual responses to foods, with the aim of advancing precision nutrition science and individualized dietary advice. The study incorporates both standardized and controlled dietary intervention, for the purpose of testing postprandial responses to specific mixed meals, in addition to a free-living period with a dietary record for measuring responses to a large variety of meals consumed in a realistic context, where the role of external factors (e.g. exercise, sleep, time of day) on postprandial responses may be determined. For the first time this PREDICT study is built on top of a commercial product which will allow access to a much larger group of participants who are already collecting large amounts of data through digital and biochemical devices that can contribute to science.