Clinical Research Directory

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.

Restoration of the Gut Microbiome After Cesarean Section

This study aims to develop a therapy for restoring the gut microbiome in infants born via CS. The Study will conduct a randomized, placebo-controlled feasibility trial to assess the ability of microbiome restoration by FMT and FVT in infants born by cesarean section.

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.

Determination of Vaginal Colonization and the Effect of an Oral Probiotic (PROSALVAG)

The aim of this study is to determine the efficacy of an oral nutraceutical with probiotics in restore vaginal health.

The Genital Microbiome of Male Partners of Women With Recurrent BV Undergoing Vaginal Microbiome Transplantation

There is strong observational evidence that sexual activity plays a key role in Bacterial Vaginosis (BV) acquisition and recurrence. Microbiological data support the contribution of sexual transmission to the pathogenesis of BV through the exchange of BV-associated bacteria (BVAB) between sexual partners. Although BV epidemiology strongly suggests sexual transmission, treatment of sexual partners is not recommended, based on prior treatment studies of male partners of women with recurrent BV, which showed no benefit with male treatment. Nevertheless, male condom use is highly protective against recurrent BV. This study aims to evaluate the male-partner's genital microbiome as a potential source of BV-recurrence in women undergoing vaginal microbiota transplantation (NCT04517487), and whether disinfection can eliminate BV-associated penile microbiome.

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.

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.

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.

FMT for Lung and Associated-organ Rescue Efficacy in MDRO-infected Ventilated Patients

Multidrug-resistant organism (MDRO)-infection 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 MDRO-infecction 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 MDRO-infecction-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 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 MDRO-infeccted ventilated patients. The primary objective is to evaluate whether adjunctive FMT-delivered via nasojejunal tube-decrease 28-day mortality.

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

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.

The Influence of Endurance Sports Activity on the Oral Microbiota of Young Adults.

The oral cavity is an easily accessible anatomical site that accurately reflects the health of the individual. The mouth is considered an early indicator of biological aging, leading to the identification of oral biomarkers predictive of future alterations. Current data show that the oral health of high level athletes is globally altered with an increase in cariogenic indexes, an increased incidence of periodontitis, dental trauma and dry mouth syndromes. Few studies have focused on the oral microbiota compared to mouthguards used in rugby or boxing which seem to induce dysbiosis, a recent study shows an effect of ketogenic diet on bacterial changes in the mouth of endurance athletes. This project focuses on the impact of intensive sport practice on oral health and the identification of oral biomarkers associated with physical activity. The objective of this study is to investigate the impact of the amount of endurance sport practice on oral microbiota and oral health in young adults. the hypothesis is that a sedentary lifestyle and high-level sport induce depletion and/or changes in the oral microbiota compared to regular physical activity.

The Milk, Growth and Microbiota Study

Late preterm infants, who are born at 34, 35 or 36 weeks gestation, often have difficulty feeding, establishing growth, and fighting off infection. Breastfeeding provides improved nutrition to help fight infection, in part because breast milk encourages the growth of healthy bacteria (microbiota) in the infant's intestine. However, when mothers give birth preterm, their breasts are usually not quite ready to make milk; it can take several days to have enough breast milk to match a baby's nutritional needs. If there is not yet enough breast milk, formula is often used. However, formula can interfere with the growth of healthy intestinal bacteria. An alternate nutritional option is donor milk from a certified milk bank, which is available in all neonatal intensive care units (NICUs) in San Francisco. However, no scientific studies have yet studied donor milk for late preterm infants, so currently all San Francisco NICUs (as well as the large majority of NICUs nationwide) reserve donor milk for infants born at \<34 weeks. This study's investigators therefore propose the "Milk, Growth and Microbiota (MGM) Study," a randomized controlled trial to compare banked donor milk to formula for breastfeeding late preterm infants born in San Francisco. Once enrolled in MGM, infants will be randomly assigned to receive either formula or banked donor milk if they need additional nutrition until their mothers are making enough milk. After enrolling the babies, investigators will weigh them daily to assess their growth. The investigators will also collect infant bowel movements at baseline, 1 week and 1 month to determine whether donor milk vs. formula impacts the type of bacteria in the baby's intestine. If the study's results show that donor milk optimizes growth while helping establish healthy bacteria in the baby's intestine, donor milk might be postnatal strategy to bolster neonatal nutrition for late preterm infants.

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.

Matching Donor Human Milk On Maternal Secretor Status (MMOMSS) Study

This study will evaluate the impact of matching donor human milk to the maternal secretor status of very preterm infants (\<34 weeks gestation) on the gut microbiome. Half of enrolled infants will receive donor human milk which is matched their mother's secretor status and half will receive standard (unmatched) donor human milk, which is standard care in the neonatal intensive care unit.

Microbiome Modulation by PEMF on Plaque Induced Mucositis in Human Jaws

To evaluate the impact of Pulsed Electromagnetic Field (PEMF) on mucositis induced in humans around dental implants and correlate these possible effects with the proteomic profile of implants with and without PEMF and teeth. The hypothesis is that PEMF may modulate bacterial biofilm formation around dental implants and enhance the host response following plaque-induced peri-implant mucositis. Secondary analysis will be the increase in the soft tissue volume using Intra-oral scanning (IOS).

Microbiome Derived Metabolism and Pharmacokinetics

The investigators will perform single-dose pharmacokinetic (PK) studies in humans following administration of drugs with known microbiome derived metabolism (MDM) in parallel with preclinical studies. By directly comparing laboratory measurements to clinical results, the investigators will be able to confirm the relevance of MDM in vivo, create microbiome-dependent PK profiles of the MDM positive drugs, and establish methodology to capture the contribution of MDM to inter-individual variability in clinical drug PK profiles.

Balance, Autonomic Response, and Sensory Modulation to Dosage of Mechanical Vagal Stimulation in Healthy Adults

The vagus nerve (VN) plays a crucial role in regulating vital functions (heart rate, blood pressure, digestion, and immune response) and maintaining communication between internal organs and the brain. Recent studies have highlighted the therapeutic potential of VN stimulation (VNS) in treating various conditions such as drug-resistant epilepsy, postural control deficit, COVID-19 infection, chronic pain, and intestinal disorders. In addition, there is growing evidence that the molecules released by the VN neurons affect the function of the gut microbiota and that the molecules released by the bacteria in our gut affect the activity of the VN neurons. In particular, Dr. Giacomo Carta (the leader of this study) has shown how painless neck movements, i.e. mechanical VNS (mVNS), can be applied without adverse effects, representing a potential alternative to invasive methods commonly used today. To further investigate the impact of this novel mVNS, this study aims to evaluate the changes induced by three mVNS protocols on physiological parameters such as resting heart rate, and Heart Rate Variability (HRV) at rest, balance in standing, the perceived intensity of mechanical stimuli using the established clinical method of QST (quantitative sensory testing), fecal transit speed, and the molecular composition of stool (for this, stool samples are analyzed). In particular, stool analysis is very relevant for understanding normal digestion. The present research aims to define the optimal intensity of mVNS and to investigate the therapeutic potential of VNS in the treatment of autonomic dysfunction (such as too low or too high heart rate, too low or too fast digestion, throbbing headaches), as well as falls prevention and pain.

Microbiome and Malnutrition in Pregnancy

This study is being conducted to investigate how a mother's nutritional status and her gut microbiome during pregnancy contribute to the birth outcomes and health of her baby. The gut microbiome is the totality of microorganisms (e.g. bacteria, viruses, fungi) living in the gastrointestinal tract. This study will focus on pregnant women, 28 years and younger living in the Toronto and greater Toronto area. The focus is on younger women due to their vulnerability to undernutrition. Pregnant participants, and upon delivery, their newborns will be followed throughout pregnancy and for a year afterwards. Throughout this period, the investigators will collect stool samples, rectal swabs, blood samples, health assessments, nutritional and dietary assessments and birth/ labour details. The goal is to define the relationship between a mother's nutritional status and her microbiome dynamics during pregnancy and how they contribute to the birth outcomes and growth of her newborn. With the hypothesis that alterations of the microbiota in the maternal gut (dysbiosis) exacerbated by nutritional status or pathogen exposure during pregnancy, impacts weight gain because of impaired nutrient absorption, leading to corresponding negative birth outcomes.

The Role of the Human Microbiome in Patients After Pancreatic Resection.

The goal of this observational study is to classify patients that undergo pancreatic resection for presumed pancreatic or periampullary malignancy into high and low risk groups for postoperative complications based on longitudinal saliva, rectal/faecal, tumor, blood and/or bile microbiome profiles. To identify the dynamics of the microbiome, as well as the possibly related short-term and long-term complications, multiple samples at different timepoints are needed from the patients.

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.

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.

Analysis of the Microbiota and STEMI

Hyperglycemia is a common finding in patients diagnosed with acute coronary syndrome (ACS), and an independent predictor of mortality in patients with and without diabetes. Though percutaneous coronary intervention (PCI) is the cornerstone of ST-segment elevation myocardial infarction (STEMI), the incidence of heart failure, re-infarction and death in hyperglycemic patients remains significant, with a mortality of more than 40% one year after the event. In these STEMI patients dual anti-aggregation therapy is currently the gold standard after PCI, but bleeding phenomena, and therapeutic resistance may reduce their therapeutic efficacy. Therefore, it is likely that the individual response to the dual anti-aggregation therapy, and the hyperglycemic stress, may influence resistance mechanisms, and/or lead to an increase in pharmacological functional deactivation by the microbiotic flora. The term microbiota indicates the totality of the genomes of microorganisms that reside in an ecological niche, and which constitute the "human microbiota". In this context, the analysis of the faecal microbiota before PCI, at hospital discharge and at follow-up, could be considered useful for identifying hyperglycaemic patients with alteration of metabolic-oxidative processes, and pro-thrombotic correlates with worse post procedural prognosis. Therefore, the analysis of faecal microbiota during the STEMI event could theoretically identify hyperglycemic patients with excessive inflammatory and oxidative tone caused by hyperglycemia, conditioning resistance to double anti-aggregation therapy and coronary stenting, and conditioning pro-thrombotic phenomena after coronary reperfusion by PCI. Therefore, authors will conduct a study to analyze the microbiota in patients with acute hyperglycaemic and normoglycemic coronary syndrome. The primary objective of this study will be to evaluate any changes in the microbiota and its activity on faecal material taken before PCI, and after 6 and 12 months in patients with hyperglycemic STEMI, and also evaluate if the changes in the microbiota can be related to the 12-month prognosis.

Effects of Tagatose on Glycemic Response and Gastrointestinal Microbiota in Healthy Adults

The primary objective of this clinical-trial is to determine, in subjects with impaired fasting glucose (IFG) and/or insulin resistance (IR), if tagatose meets the definition of a prebiotic, namely that consuming tagatose for 4 weeks selectively stimulates the selective growth of bacteria in the colon and is associated with a health benefit (oral glucose tolerance) when compared to consuming the control treatment (10g sucrose) for 4 weeks.