50 Clinical Trials for Various Conditions
The MiSBIE study collects biological, behavioral, psychosocial, neuropsychological, and brain imaging data in participants with either: normal mitochondrial function, individuals with the m.3243A\>G mitochondrial DNA (mtDNA) mutation, and individuals a single large-scale mtDNA deletion. These defects induce mitochondrial allostatic load (MAL). The 2-day protocol, plus home-based data collection, will provide a comprehensive assessment of the multi-systemic dysregulation associated with MAL or mitochondrial dysfunction, and the link to physical and mental health-related symptoms. Aim 1: Determine the influence of MAL on systemic AL biomarkers. Aim 2: Establish the influence of MAL on stress reactivity profiles. Aim 3. Examine the association between MAL and psychological functioning.
The primary purpose of this multi-centre, randomized, placebo-controlled, double-blind phase II study is to investigate if oral vitamin C may change the biology of low-risk myeloid malignancies; i.e., clonal cytopenia of undetermined significance (CCUS), low-risk myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML)-0/1 by reversing the epigenetic changes characteristic of these disease entities. The epigenetic regulator TET2 is the gene most often affected in CCUS. Preclinical studies have shown that active demethylation by the TET enzymes is dependent on vitamin C, and the investigators and collaborators have shown that plasma vitamin C levels are exceedingly low in hematological cancer patients but are easily corrected by oral vitamin C. This study is part of an array of EVITA studies aimed at clarifying whether the standard of care of patients with myeloid malignancies should be changed and oral vitamin C supplement added to the treatment recommendations.
The PHITE collaborative team, consisting of Tim Broderick, MD (Overall PI), Wright State University (WSU); Marcas Bamman, PhD (Site PI), The University of Alabama at Birmingham (UAB); and Ron Evans, PhD and Joe Ecker, PhD, Salk Institute for Biological Studies, are working with funding from the US Department of Defense (DoD), Office of Naval Research (ONR), to explore the link between physical training and epigenetics. This is a key interest area for the DoD ONR because it provides high-impact optimization of force readiness in warfighters with diverse backgrounds. The term epigenetics refers to heritable changes in gene expression (active versus inactive genes) that does not involve changes to the underlying DNA sequence; a change in phenotype (the set of observable characteristics of an individual resulting from the interaction of its genotype with the environment) without a change in genotype (the genetic constitution of an individual organism) . This in turn affects how cells read the genes. Epigenetic change is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. Epigenetic modifications can manifest as commonly as the manner in which cells terminally differentiate to end up as skin cells, liver cells, brain cells, etc. New and ongoing research is continuously uncovering the role of epigenetics in a variety of human conditions. This study is designed to assess whether epigenetics is a primary mechanism modulating how individuals adapt to specific exercise training prescriptions designed to produce a warfighter phenotype. The PHITE team is organized around a shared test population of human subjects for which UAB will oversee recruitment, training, testing, and sampling. Healthy but untrained volunteers, both men and women, 18-27 y of age-phenotypical of the US warfighter-will participate in a 12-wk, two-arm, single-blind, randomized, exercise dose-response trial comparing two intensities of combined training: Moderate-Intensity vs. High-Intensity. Biospecimens are collected before and after an acute exercise bout in the pre-training state, and again after 12 weeks of 3 d/wk combined exercise training. Numerous phenotyping assessments are collected before after the 12-week intervention period to associate exercise training outcomes with molecular changes in the skeletal muscle and blood biospecimens.
This study examines the relationship among epigenetic alterations and the development and persistence of psychoneurologic symptoms (cognitive dysfunction, depressive symptoms, anxiety, fatigue, sleep disturbance, and pain) in women receiving chemotherapy for early stage breast cancer. The relationship among inflammatory markers and psychoneurologic symptoms will also be explored. It is hypothesized: 1. Chemotherapy triggers inflammatory activation, which in turn leads to the acquisition of genetic alterations. These alterations result in cellular changes and are modified over time. 2. Inflammatory activation and epigenetic alterations are related to the temporal development, severity, and persistence of psychoneurologic symptoms.
The goal of this clinical trial is to assure the safety of long term therapeutic plasma exchange (TPE) with and without Intravenous Immunoglobulin (IVIG) and its effects on biomarkers and epigenetic biologic clocks in forty individuals. The main question is to assure the safety from long term TPE using changes in clinical and laboratory outcomes and also evaluating changes on additional blood biomarkers and epigenetic clocks during and after TPE treatment. Researchers will compare the TPE treatment group to the Sham treatment group to identify changes due to TPE. Participants will receive six TPE or Sham treatments over one of two treatment schedules and may receive IVIG with treatment.
This is an add-on substudy to an already-approved clinical trial "A Multi-Site Phase 3 Study of MDMA-Assisted Psychotherapy for PTSD" (ClinicalTrials.gov Identifier: NCT03537014) which is to be a phase 3 clinical trial studying the efficacy of MDMA-Assisted Psychotherapy for Post Traumatic Stress Disorder. The parent study has been approved by Copernicus Group IRB and is being run by the MAPS Public Benefit Corporation, and is a randomized controlled trial comparing the clinical efficacy of MDMA-assisted psychotherapy to Placebo-assisted psychotherapy. The parent study will recruit participants with Post Traumatic Stress Disorder and involves 20 total study visits over the course of 18 weeks including 3 preparatory psychotherapy visits plus 3 separate treatment sessions involving psychotherapy plus the administration of MDMA vs. placebo and 3 follow up psychotherapy visits after each treatment session. This substudy adds on the collection of saliva in a salivary DNA collection kit at baseline and after treatment to the parent study clinical trail so as to assess whether the MDMA-Assisted Psychotherapy exerts influence on the epigenetic regulation of stress-associated genes as assessed in the salivary epithelial and white blood cells of the research participants. We aim to further assess whether any such changes are correlated with improvements in PTSD symptoms.
Background: Early evidence in the COVID-19 pandemic suggests that smokers are at a higher risk of having severe effects or dying from the disease. Smoking causes changes in immune cells. Researchers think this may be the reason why smokers are more likely to have severe effects from COVID-19. Researchers want to better understand the interaction between smoking history, the immune system, and COVID-19. Objective: To better understand how COVID-19 affects smokers and non-smokers immune systems before and after being infected with the virus. Eligibility: Healthy people ages 30-55 who are a smokers or non-smokers who may potentially contract COVID-19 Design: Participants will be screened over the phone. They will answer questions about their demographics, medical history, medications, and smoking status. Participants will have up to 6 monthly visits. At the first visit, participants will have blood tests. Blood will be drawn through a needle in an arm vein. They will provide a saliva sample in a container and have a cheek swab. The participant will also have a nasal swab to see if they currently have COVID-19. Their height and weight will be taken. They will complete questionnaires about their medical history and smoking status. Participants will then have monthly visits. They will have blood draws to test for COVID-19 antibodies. They will provide a saliva sample in a container and have a cheek swab. The participant will also have a nasal swab to see if they currently have COVID-19. These visits will occur 4 times or until they have a positive antibody result. Participants will have a final visit. They will have blood tests. They will provide a saliva sample in a container and have a cheek swab. The participant will also have a nasal swab to see if they currently have COVID-19. If at any time participants test positive for a COVID-19, they will be rescheduled 14 days or more after they no longer have symptoms....
A key tenet of this project is that of reaching translational human diagnosis and biomarker end points. To lay a foundation and make progress towards these translational goals, investigators will address the following specific aim: To determine if BMI/ obesity differentially influence expression and epigenetic signatures in triple negative breast cancer (TNBC) from Hispanic compared to NHW women.
Through a recent cross species translational experiment, researchers have identified a set of epigenetic marks capable of predicting postpartum depression with greater than 85% accuracy. The researchers are looking to identify a group of women from both the general population and those with a history of mood disorders who are at risk for postpartum depression and obtain brain imaging data at a postpartum time period prior to the onset of depressive symptoms and compare it with those obtained during depressive episodes. The researchers will also evaluate the efficacy of postpartum depression biomarker prediction.
This study seeks to examine genome-wide DNA methylation patterns associated with physical activity and exercise capacity from peripheral blood collected from participants with chronic obstructive pulmonary disease (COPD) before and after participation in a structured 9-week outpatient pulmonary rehabilitation program.
The investigators are trying to understand the role of DNA (deoxyribonucleic acid) methylation in insulin resistance in skeletal muscle and blood tissues. DNA methylation is a normal chemical process in the body that modifies DNA. By studying this, the investigators hope to better understand the causes of insulin resistance.
This study will recruit women with post partum pre-eclampsia and match them to controls without postpartum pre-eclampsia to identify an epigenetic signature that is specific to women with post partum pre-eclampsia to help characterize the underlying pathophysiology of post partum pre-eclampsia.
The investigators are trying to understand the role of DNA (deoxyribonucleic acid) methylation in insulin resistance in skeletal muscle and blood tissues. DNA methylation is a normal chemical process in the body that modifies DNA. By studying this, the investigators hope to better understand the causes of insulin resistance.
The overall goal of this research is (1) to identify changes in gene expression and DNA methylation status in subjects who exhibit advanced chronic periodontal inflammation and (2) to identify microRNAs (miRNAs) and the interactive pathways associated with obesity as a modifier of periodontal infection pathogenesis.
As part of ongoing efforts to determine the causes of asthma and the progression of the disease, this study will gather data to explore the interaction of genetic and environmental factors in the cause and severity of asthma in inner city children.
This study will examine the role of epigenetics (heritable changes in gene function that occur without a change in DNA sequence) in the aging process. DNA is the primary genetic material, responsible for transmitting information from one cell to the next or from one generation to the next. A second layer of heredity is described by the term "epigenetics." Epigenetic information is reset from one generation to the next. It works in two ways: 1) by modification of the DNA, like balloons stuck at irregular intervals onto the sides of the DNA helix that encodes genes, and 2) through specialized protein shells that wrap around some regions of DNA. As in DNA, these shells can copy themselves and can transmit instructions. Because they are used to turn genes on and off, errors in their settings cause critical misinformation to be transmitted. Aging involves many changes, such as muscle weakening, graying hair, skin wrinkling, and so forth. There are several current theories of aging, including damage to genes by oxidation, shortening of tiny structures at the ends of chromosomes called telomeres, and the ability to stretch lifespan with caloric restrictions. This study will investigate the possible role of epigenetics in aging by examining and comparing the shell-like epigenetic settings in skin cells in young adults and older individuals. Preliminary results from earlier studies show differences in these settings in younger and older people. Women between the ages of 21 and 30 years and 65 and 90 years who are undergoing breast reduction or mastectomy at Suburban Hospital in Bethesda, Maryland, may participate in this study. Tissue removed during surgery for pathological examination will also be used by researchers in this study to validate the preliminary findings noted above and to continue studies into the new area of epigenetics and aging. ...
This is a single center, prospective study to evaluate correlations between epigenetic aging (as measured via DNA methylation) and NAD+ levels in healthy volunteers.
This study tests the effectiveness of dietary interventions that have the possibility to improve markers of gut health and improve general well-being. This study will allow healthcare professionals to learn how dietary interventions involving fasting can affect health. Food is increasingly recognized as a core component of preventive and ameliorative health care. Juice fasting has quickly become one of the most popular self-prescribed dietary interventions in the United States. A wide variety of juice fasts are available in the popular market; a popular variation is the three-day juice fast. The purpose of this study is to assess the effects of a three-day juice fast on certain markers of age-related disease and bio-markers of longevity. In particular, this study will assess certain epigenetic markers, which measure how the environment (including diet) can change the way that genes are expressed without changing the genes themselves. The study will also assess the microbiome, and inflammatory and glycemic markers.
Topical Rapamycin ointment will be applied to participant forearms to test whether epigenetic changes in the skin are elicited.
The molecular mechanisms underlying developmental programming of childhood obesity remain poorly understood. Here, the investigators address major questions about early childhood obesity programming by studying CD3+ T-cells from intrauterine growth restricted (IUGR) newborns who have an increased risk for obesity and other metabolic disorders in adult life.
This research is being done to examine epigenetic markers and mood changes across the menstrual cycle, particularly in premenstrual dysphoric disorder (PMDD). The investigators previously identified epigenetic biomarkers of postpartum depression, another reproductive affective disorder, and in this study aim to determine if these biomarkers also distinguish PMDD cases from healthy controls at different points in the menstrual cycle. By collecting biological samples (such as blood) and monitoring mood changes across the menstrual cycle, the investigators will be able to determine whether these epigenetic markers are associated with PMDD. The investigators plan to study these epigenetic markers during the follicular phase (roughly the first half of the menstrual cycle, from menses until ovulation) and the luteal phase (roughly the second half of the menstrual cycle, from ovulation to menses). The investigators will study this in two groups: 1) individuals who do NOT have premenstrual mood symptoms, and 2) individuals with premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD). The results will provide a comprehensive view of the changes in these systems across the menstrual cycle. This will add to the investigators understanding of the mechanisms that may cause PMS/PMDD.
The goal of this observational study is to understand how genomic and epigenetic factors contribute to resistance against chemo-immunotherapy in adults diagnosed with extensive-stage small cell lung cancer (ES-SCLC) or metastatic large cell neuroendocrine carcinoma (LCNEC). Both ES-SCLC and LCNEC are aggressive forms of lung cancer with limited treatment options and poor prognosis. While initial responses to chemo-immunotherapy are often promising, most patients develop resistance within a few months, resulting in disease progression and limited survival. This study seeks to explore the molecular and cellular changes that drive resistance, providing insights that could guide more personalized and effective treatment strategies in the future. The study focuses on identifying genomic and methylation signatures, as well as analyzing circulating tumor cells (CTCs) and tumor DNA (ctDNA), to better understand the mechanisms of resistance. By collecting and analyzing these biomarkers over time, researchers aim to identify patterns that distinguish patients who benefit long-term from therapy from those who experience early resistance. These findings may pave the way for new diagnostic tools and therapies to predict and overcome resistance to chemo-immunotherapy. The main questions this study seeks to answer are: Are there specific genomic or methylation patterns that predict resistance to chemo-immunotherapy in ES-SCLC and LCNEC? How are circulating tumor cells (CTCs) and tumor DNA (ctDNA) associated with disease progression, treatment response, and survival? What molecular differences exist between patients who respond long-term and those who develop resistance early in their treatment? Participants will: Provide blood and tumor tissue samples before treatment to establish baseline molecular profiles. Undergo follow-up visits every 9 weeks during treatment, where additional blood samples and imaging tests will be collected to monitor disease progression and treatment response. Optionally provide tissue samples through re-biopsy if the disease progresses, enabling researchers to compare changes in tumor biology over time. All blood and tissue samples will be de-identified and securely stored for genomic and epigenetic analyses. Blood samples will be examined for circulating tumor cells and tumor DNA, while tumor tissue samples will undergo in-depth genomic and methylation profiling. Researchers will use advanced molecular and bioinformatics techniques to uncover specific patterns associated with resistance, aiming to improve current treatment strategies and develop more precise therapies. The study will analyze data from patients over three years, encompassing various stages of treatment and disease progression. By examining longitudinal samples, the study aims to capture the dynamic changes that occur in the tumor microenvironment and how these relate to treatment outcomes. This research is particularly important because current treatment options for ES-SCLC and LCNEC are limited, and there are no established methods to predict which patients will respond to chemo-immunotherapy. Identifying biomarkers of resistance could transform clinical care, allowing oncologists to tailor treatments to individual patients' molecular profiles and improve survival outcomes. Ultimately, the findings from this study could lead to the development of new biomarkers for resistance, improve early detection of treatment failure, and provide the foundation for novel therapies targeting resistant cancer cells. By addressing a critical gap in the understanding of resistance mechanisms, the STRATUS trial has the potential to significantly advance the field of personalized oncology.
Premenstrual dysphoric disorder (PMDD) is a severe affective disorder impacting millions of women worldwide, thought to be due to altered sensitivity to hormone fluctuations across the menstrual cycle. Neuroactive steroid hormones (NAS) and the gamma-aminobutyric acid (GABA)-A receptor (GABAAR) are thought to play a role in PMDD. This research will assess the blood levels of GABAergic NAS, expression of associated enzymes, and expression of GABAAR subunits across the premenstrual (luteal) phase of the menstrual cycle in healthy controls and individuals with PMDD. Within the PMDD group, the investigators will assess how these measures are affected by a low-dose antidepressant medication versus placebo. The results will provide a comprehensive view of the changes in these systems across the menstrual cycle and will add to the investigator's understanding of the mechanisms that underlie PMDD, as well as therapeutic mechanisms of PMDD treatment.
More than 60,000 infants are born between 22 to 32 weeks gestation age annually in the US. Approximately 11% of them develop comorbidities. During NICU hospitalization, preterm infants inevitably endure early life toxic stress without adequate protective buffers. Early life toxic stress results in adverse epigenetic modifications of glucocorticoid-related genes and dysbiosis, impairing neurodevelopment. These adversities further exacerbate the risk of comorbidities and inappropriate brain development during sensitive periods of neuroplasticity. Adverse epigenetic modifications and dysbiosis may set a life-long trajectory of risk for chronic health conditions. It is a clinical and scientific priority to test an early NICU intervention to attenuate stress-related adverse epigenetic modifications and dysbiosis. Human milk influences the structure and relative abundance of healthy gut bacteria and neurodevelopment. Maternal nurturing, e.g., licking and grooming (in rodents), and breastfeeding and touch (in humans), promotes neurodevelopment, reduces stress, and reverses stress-related epigenetic modifications. The multisensory early oral administration of human milk (M-MILK) intervention is designed to provide an enjoyable and nurturing experience for infants, through a safe and consistent infant-guided provision of human milk droplets, given orally as early as 22 weeks postmenstrual age. M-MILK is implemented from day 3 of life, after every hands-on care, and during the beginning of a full gavage feeding. We propose the M-MILK pilot randomized controlled trial (RCT): a 2-group (N = 12, 6 per group), parallel, and longitudinal design in preterm infants who are born between 22 to 28 weeks gestational age. The aims of this pilot are to determine the feasibility and acceptability of the M-MILK intervention, recruitment, retention, and obtain data for sample size estimation. This study will advance nursing science and practice because it will inform our R01 RCT to examine the efficacy of M-MILK to attenuate adverse effects of early life toxic stress in preterm infants.
The overall aims of this protocol are to determine whether prenatal supplementation with vitamin C to pregnant smokers can improve pulmonary function at 10 years of age in their offspring. This is an additional continuation of the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) trial, to follow the offspring through 10 years of age. The hypothesis for this protocol is an extension of the VCSIP trial that supplemental vitamin C in pregnant smokers can significantly improve their children's airway function tests. The investigators aim to demonstrate sustained improvement in airway/pulmonary function and trajectory through 10 years of age.
The goal of the study is to validate the ability of the Epigenetic Sperm Quality Test (SpermQT) to assess a man's sperm quality and corresponding success of infertility treatments.
This is a Phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a single agent and in combination with standard of care in patients with hepatocellular carcinoma (HCC) and other solid tumor types known for association with the MYC oncogene. The study consists of Part 1 (OTX-2002 monotherapy) and Part 2 (OTX-2002 combined with standard of care in hepatocellular carcinoma). Part 1 consists of escalation and expansion, and Part 2 consists of safety run-in and expansion. The objective of Part 1 escalation and Part 2 safety run-in will be safety and tolerability, while anti-tumor activity will be evaluated as the primary endpoint in Part 1 and Part 2 expansion.
American Indian populations continue to suffer disproportionately from health problems including such nutrition-related chronic diseases as diabetes and heart disease. This research project will therefore investigate how a traditional Indigenous food called chokeberry (Aronia melanocarpa) impacts epigenetic and metabolic health in relation to resiliency markers in American Indian participants. The process of research with American Indian communities is significant in that it can inform best practices in community engagement orientations, approaches, and models in future research settings.
The main objective is to examine DNA hypomethylation as an underlying mechanism for the increased production of inflammatory cytokines and the impaired vascular function in obese individuals and as a potential target for nonpharmacological preventive/therapeutic interventions such as aerobic exercise.
This study is a non-interventional, specimen collection translational study to evaluate vitamin C levels in the peripheral blood of Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), or Chronic Myelomonocytic Leukemia (CMML) patients.