cyrilzakka/clinical-trials huggingface dataset:
Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TJ107 in Chinese Patients With Advanced Solid Tumors

This is a two-part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of TJ107 in Chinese patients with advanced solid tumors. Approximately a total of 36 \~ 60 patients will be enrolled into the dose escalation cohorts (Part A), and expansion cohorts (Part B).


Eligibility Criteria:
Inclusion Criteria:

* Aged at least 18 years old;
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~2;
* Patients must have histological or cytological confirmation of advanced solid tumors that is refractory to standard therapy or for which there is no standard available therapy;
* Predicted life expectancy ≥3 months;
* Patients must have adequate organ and marrow function;
* Patients at reproductive age should take adequate contraceptive measures while on study drug and for 6 months following the last dose of study drug.
* Patients should have the ability and willingness to comply with the study and follow up. And patients must be able to provide written informed consent.

Exclusion Criteria:

* Patients who have experienced a Grade 3 or higher toxicity related to prior immunotherapy.
* Patients who are still receive anti-tumor therapy such as radiotherapy, chemotherapy, targeted therapy, endocrine therapy, or other clinical trials from 4 weeks prior to the first dose, or patients who have not recovered from previous toxicity to level 1.
* Women who are pregnant or breast feeding
* Patients who are drug-dependent or have a history of substance abuse or psychonosema history.
* Have been vaccinated within 4 weeks of study dosing, with the exception of licensed intranasal or intramuscular influenza vaccine during study
* Prior allogeneic bone marrow transplantation or prior solid organ transplantation
* Positive laboratory test for HBsAg with HBV DNA ≥ 100 IU/mL, or positive laboratory test for HCV.
* Prior treatment with immune checkpoint inhibitors, immunomodulatory mAbs, and/or mAb-derived therapies is allowed provided that at least 3 months or 5 half-lives of the drug, whichever is longer, have elapsed from the last dose.
* Uncontrolled concurrent illness.
* Major surgery procedure (excluding diagnostic surgery) within 4 weeks of the first dose of study drug.
* Patients with a history of treated CNS metastases.
* Other psychiatric illness/social situations that would limit compliance with the study requirements decided by the investigator.
Cardiac MRI for Optimal Heart Failure Outcomes With CRT Upgrades

This study will investigate the use of cardiac MRI in patients with standard ICDs and pacemakers to inform how cardiac resynchronization therapy (CRT) can best be implemented in these patient and which patients are the best candidates for CRT.

The scientific premise of this proposal is that left and right ventricular (LV and RV) structural characteristics in patients with existing cardiac implantable electronic devices and heart failure who may benefit from an upgrade to a cardiac resynchronization therapy (CRT) device can be assessed very effectively using cardiac MRI using sequences designed for post-device imaging. Furthermore, a comparative analysis of the differences in LV/RV structural characteristics in patients with existing devices referred for CRT upgrades versus those with de novo CRT implants is expected to be very useful for developing effective strategies for optimal patient selection for CRT upgrades and implementation of CRT upgrades in appropriate patients. Patient selection for CRT upgrades is very important considering that complication rates are higher than in de novo CRT procedures and nonresponse rates are still high. With this in mind, we are performing a study of 100 patients, including 50 prospectively enrolled patients with LVEF less than or equal to 0.35 and New York Heart Association class II-III heart failure, who will be compared with an existing cohort of 50 patients with recent de novo CRT implants, pre-CRT MRIs, and response data. The 50 prospectively enrolled patients having CRT upgrades will undergo a pre-CRT cardiac MRI, pre-CRT/post-CRT echocardiography, and pre-CRT/post-CRT cardiopulmonary exercise testing. In the first aim, we will assess differences in cardiac MRI findings between CRT upgrade patients and de novo CRT patients. In the second aim, we will assess the impact of cardiac MRI findings on LV reverse remodeling and cardiopulmonary capacity in the two groups. In summary, we propose a comprehensive prospective CRT/MRI study in CRT upgrade patients with comparison to a complete MRI dataset of patients with de novo CRT implants in order to identify key differences in MRI findings in these cohorts and the impact of these MRI-based scar and activation findings on clinical outcomes. We expect that our results will have a significant public health impact for patients with heart failure referred for CRT upgrades.

Eligibility Criteria:
Inclusion Criteria:

- Undergoing upgrade from an existing pacemaker or ICD to a CRT device.

Exclusion Criteria:

* inability to provide informed consent
* pregnancy
* presence of metal embedded in the body due to prior accident or injury, as documented by skull films or other imaging
* cerebral aneurysm clips
* cochlear implants
* other metallic implants known to be contraindications to MRI (pacemakers and ICDs are allowed)
* severe claustrophobia
* acute kidney injury
* acute renal failure
* gadolinium allergy
* abandoned leads
Evaluation of the Healthy Lifestyle Program on Cognitive Outcomes

The goal of this study is to conduct a program of pilot research aimed at evaluating the effect of an intensive lifestyle intervention on cognitive functioning in older adults with obesity and or obesity and sarcopenia.

Detailed Description:

The national epidemic of obesity is also affecting older adults, and is associated with an increased risk of disability, nursing home placement and early mortality. The overarching goal of this study is to conduct a program of pilot research aimed at evaluating the effect of a intensive lifestyle intervention on cognitive functioning in order adults with obesity and or obesity and sarcopenia. While some degree of cognitive decline is common during the normal aging process, epidemiological evidence suggests that obesity can promote its acceleration. It is unclear the effect that intensive lifestyle changes could have on cognitive functioning in older adults with obesity.

Study Timeline:

May 2019 to May 2023

Goal: Conduct a study to evaluate the effects that intensive lifestyle program has on cognitive functioning in older adults with obesity and or obesity and sarcopenia.

Participation Duration: Participants will meet weekly for 17 weeks. Cognitive assessments will take place at baseline and 17 weeks.

Eligibility Criteria:
Inclusion Criteria:

* English Speaking
* Age ≥65 years
* Body Composition Body Fat \>25% for Men
* Body Composition Body Fat \>30% for Women
* Participating in the Dartmouth Hitchcock Weight and Wellness Center (WWC) Healthy Lifestyle Program (HLP)
* Willing and able to give informed consent

Exclusion Criteria:

* Unable to perform measures
* Individuals unwilling/unable to provide consent
* Severe mental or life-threatening illness
* History of bariatric surgery
Treatment of Hyperuricemia in Patients With Heart Failure

The study aims to assess (I) the contribution of UA itself to the CHF pathophysiology and (II) to test the effect of lowering UA by uricosuric treatment in CHF.

Hyperuricemia is often observed in patients with congestive heart failure (CHF). It has been reported that hyperuricemia is related to exercise capacity, inflammation markers and diastolic dysfunction in such patients. In addition, hyperuricemia in CHF relates to both symptomatic status (i.e. morbidity) as well as impaired prognosis (i.e. mortality). Hyperuricemia is likely to play an important role in the pathophysiology of CHF. Up-regulation of xanthine oxidase (XO) activity in CHF has been shown to contribute to higher uric acid (UA) in CHF and the therapeutic concept of XO inhibition has shown beneficial effects in a number of surrogate markers in these patients. The XO inhibition accounts for substantial decrease in oxygen radical load, the latter is discussed as the main benefit of XO inhibition treatment in hyperuricemic patients. However, whether high uric acid itself is important or merely a marker of XO activity (and hence of increased radical accumulation) is currently under discussion. Therefore, this study aims to assess (I) the contribution of UA itself to the CHF pathophysiology and (II) to test the effect of lowering UA by uricosuric treatment in CHF.

Eligibility Criteria:
Inclusion Criteria:

* chronic heart failure
* hyperuricemia

Exclusion Criteria:

* renal dysfunction (Cr \> 2.0 mg/dl)
* under treatment with anti-diabetic agents
AssesSment of Early deteCtion basEd oN liquiD Biopsy in Intracranial Tumors

ASCEND-BRAIN is a prospective, observational study aimed at early-detection of intracranial tumors by combined assays of cfDNA methylation and other biomarkers. The study will enroll approximately 358 participants including intracranial malignant tumors, patients with benign disorders of central nervous system and healthy participants.


Eligibility Criteria:
Inclusion Criteria for Cancer Participants:

* Age 40-75 years
* Ability to provide a written informed consent
* Pathologically confirmed diagnosis or highly suspicious cases of intracranial malignant tumors
* No prior or ongoing anti-cancer treatment (local or systematic) prior to study blood draw

Inclusion Criteria for Benign Disease Participants:

* Age 40-75 years
* Ability to provide a written informed consent
* Pathologically confirmed diagnosis or highly suspicious cases with benign disorders of central nervous system
* No prior or ongoing radical treatment of the benign disorders of central nervous system prior to study blood draw

Inclusion Criteria for Healthy Participants

* Age 40-75 years
* Ability to provide a written informed consent
* No cancer-related symptoms or other uncomfortable symptoms prior to study blood draw

Exclusion Criteria for All Participants:

* Insufficient qualified blood samples
* Recipient of organ transplant or prior non-autologous (allogeneic) bone marrow or stem cell transplant
* Recipient of blood transfusion within 7 days prior to blood draw
* Recipient of anti-tumor drugs to treat non-cancer diseases within 30 days prior to blood draw, such as rheumatic drugs (methotrexate, cyclophosphamide, or azathioprine), or endocrine drugs (tamoxifen)

Additional Exclusion Criteria for Cancer Participants:

-Other current malignant diseases or multiple primary tumors

Additional Exclusion Criteria for Benign Disease Participants:

-Current or history of malignancies

Additional Exclusion Criteria for Healthy Participants:

* Recipient of anti-infectious therapy within 14 days prior to study blood draw
* Prior or ongoing treatment of cancer within 3 years prior to study blood draw
* Current autoimmune disease or clinically significant or uncontrolled comorbidities
Hyperoxia Induced Pulmonary Inflammation and Organ Injury: a Human in Vivo Model

Oxygen is the most commonly administered therapy in critical illness. Accumulating evidence suggests that patients often achieve supra-physiological levels of oxygenation in the critical care environment. Furthermore, hyperoxia related complications following cardiac arrest, myocardial infarction and stroke have also been reported. The underlying mechanisms of hyperoxia mediated injury remain poorly understood and there are currently no human in vivo studies exploring the relationship between hyperoxia and direct pulmonary injury and inflammation as well as distant organ injury.

The current trial is a mechanistic study designed to evaluate the effects of prolonged administration of high-flow oxygen (hyperoxia) on pulmonary and systemic inflammation. The study is a randomised, double-blind, placebo-controlled trial of high-flow nasal oxygen therapy versus matching placebo (synthetic medical air). We will also incorporate a model of acute lung injury induced by inhaled endotoxin (LPS) in healthy human volunteers. Healthy volunteers will undergo bronchoalveolar lavage (BAL) at 6 hours post-intervention to enable measurement of pulmonary and systemic markers of inflammation, oxidative stress and cellular injury.


Eligibility Criteria:
Inclusion Criteria:

1. Healthy non-smoking subjects less than 45 years of age and BMI \< 29 kg/m²

Exclusion Criteria:

1. Age \< 18 years
2. On concomitant medications including over the counter medications excluding oral contraception and paracetamol
3. Previous adverse reactions to LPS, lignocaine or sedative agents
4. Pregnant or Breast-Feeding
5. Participation in a clinical trial of an investigational medicinal product within 30 days
6. Consent declined
7. History of asthma or other respiratory conditions
8. Smoking/ e cigarette use
9. Marijuana use or other inhaled products with or without nicotine in the last 3 months
10. Alcohol abuse, as defined by the Alcohol Use Disorders Identification Test (AUDIT)
11. Subjects with history of prior conventional cigarette (\> 100 cigarettes lifetime and smoking within 6 months) or electronic cigarette use.
Effect of Isometric and Aerobic Physical Exercise on Blood Pressure Levels in Hypertensive Elderly People

Introduction: Adequate blood pressure control is necessary to reduce the risk of mortality from cardiovascular events. The effects of aerobic exercise on systemic arterial hypertension are already well known, however, to date, there is little evidence regarding the effect of an isometric exercise session for the lower limbs on blood pressure levels, especially when performed in elderly hypertensive individuals. Objective: To verify the effect of an isometric or aerobic exercise protocol for the lower limbs on 24-hour ambulatory blood pressure in elderly hypertensive individuals.

Introduction: Adequate blood pressure control is necessary to reduce the risk of mortality from cardiovascular events. The effects of aerobic exercise on systemic arterial hypertension are already well known, however, to date, there is little evidence regarding the effect of an isometric exercise session for the lower limbs on blood pressure levels, especially when performed in elderly hypertensive individuals. Objective: To verify the effect of an isometric or aerobic exercise protocol for the lower limbs on 24-hour ambulatory blood pressure in elderly hypertensive individuals.

Methods: Thirty-six controlled hypertensive volunteers, aged ≥ 60 years, of both sexes, will be randomly selected based on their medical records. Volunteers will be randomized to perform an isometric wall squat exercise session (n=12 - 4 repetitions of 2 minutes of execution and 2 minutes of rest, performed at a specific angle of the volunteer\&#39;s knee joint - Borg scale of 11 to 13 points - moderate intensity) or an aerobic exercise session on a stationary bike (n=12 - 40 minutes and at moderate intensity stipulated between the range of 50% to 60% of HR reserve and Borg scale of 11 to 13 points - moderate intensity) or a control session without exercise, 40 minutes per session (n=12). 24-hour Ambulatory Blood Pressure Monitoring will be performed pre- and post-session. Statistical analyzes will be performed using the ANOVA test (one way), power of 80% and alpha 95%, SPSS-26.0.

Eligibility Criteria:
Inclusion Criteria:

* Hypertensive elderly;
* Both genders;
* Aged ≥ 60 years;
* Hypertensive patients on continuous use of antihypertensive medication;
* Hypertensive who did not practice physical exercise regularly (≥ 2 sessions per week).

Exclusion Criteria:

* Those who presented one of the following issues will be excluded:
* Diabetes mellitus;
* Chronic renal failure;
* Body mass index (BMI) ≥ 35 kg/m2;
* Coronary artery disease;
* Heart failure;
* Any injury to the lower limbs;
* Smokers.
Conduction System Stimulation to Avoid Left Ventricle Dysfunction

The aim of the study is to demonstrate that conduction system pacing (CSP) can preserve a normal ventricular function compared to right ventricular apical pacing (RVAP) in patients with pre-implant preserved left ventricular ejection fraction (LVEF) and a high burden of expected ventricular pacing due to atrioventricular conduction block (AV block).

After informed consent signature, patients with high degree AV block and normal LVEF will be randomized to permanent pacemaker stimulation with CSP vs RVAP.

All the patients have a complete evaluation before the procedure and at 3 and 6 months follow-up.

The STAY trial (Conduction System sTimulation to Avoid left ventricle dYsfunction) is a single-center, prospective, randomized, parallel, controlled study, comparing mid-term outcomes in a population undergoing pacemaker implantation due to a high degree atrio-ventricular block (AVB). The study was approved by the Hospital Ethics Committee, in accordance with the Declaration of Helsinki. All patients signed informed consent and were implanted between September 2019 until December 2022 in a 1:1 randomized fashion to conventional RVAP vs CSP (HBS or LBBS). Randomization was performed during the pre-procedural antibiotic infusion.

All the patients have a complete evaluation before the procedure and at 3 and 6 months follow-up, including demographic and clinical characteristics, physical examination, twelve-lead ECG, Minnesota score (MLWHFQ), and blood test with NT-ProBNP determination. Patients also have a transthoracic echography before the procedure and at 6 months follow-up.

At 6 months echocardiographic and clinical data will be compared.

Eligibility Criteria:
Inclusion criteria:

1. Age of 18 years or more
2. Preserved or mild deteriorated LVEF (Simpson \>40%) assessed by a recent (\<1 month before implantation) transthoracic echocardiography.
3. Indication for pacing based on the presence of a high degree AVB, and consequently with an anticipated high burden of ventricular pacing (\>50%).
4. Live expectancy of more than 6 months and capability to understand the protocol, signing the informed consent form and accomplish the follow-up.

Exclusion criteria:

1. Indication for implantable cardioverter defibrillator device.
2. Patients with previous LVD and a recovered LVEF
3. History of myocardial infarction/revascularization or cardiac surgery within 6 months before randomization
4. Pregnancy, active cancer treatment, or participation in another clinical trial with active treatment.
Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids

Butyric acid has been shown to promote gut health and improve the microbiome in multiple adult studies. In preliminary studies in older children with inflammatory bowel disease, butyric acid was shown to be safe. However, it's suitability for infants and young children with congenital heart disease (CHD) has yet to be determined.

This study will examine butyric acid supplementation in infants and children, ages 1 month to 3 years, with CHD who require cardiac surgery with cardiopulmonary bypass. Study goals include determining the safety and tolerability of butyric acid supplementation before cardiac surgery, and to identify changes in gut microbial communities, metabolic profile, and genetic markers intestinal function. Also, the study seeks to establish a reduction in inflammation (inflammatory signaling) after cardiopulmonary bypass (CPB) in participants receiving butyric acid.

The goal of this study is to supplement a liquid form of butyric acid once daily for 3 weeks prior to cardiac surgery for infants and children, ages 1 month to 3 years, with congenital heart disease to improve their pre-operative gut microbiome in efforts to reduce post-operative gut permeability and reduce post-operative inflammatory signaling.

Up to 35 participants will be enrolled in each of three arms:

* 2 mL butyric acid
* 4 mL butyric acid
* Placebo.

Participants will be asked to:

* Provide blood and stool samples (baseline, post-supplement-pre-operative, 1-hr post-op, \& post-op days 1-3)
* Take either 2 mL, 4 mL or placebo once daily for 3 weeks prior to cardiac surgery
* Complete a daily log to track timing of supplement administration and any side effects or adverse events experienced

Study aims:

* Aim 1 Safety and tolerability will be measured following baseline complete blood counts, complete metabolic panel to evaluate electrolytes and organ function, along with a daily log of supplementation timing and any experienced adverse events.
* Aim 2 Modulation of gut health will be measured with stool and blood samples. Changes will be measured in the gut microbiome and metabolite profiles before and after supplementation, as well as post-operatively. Gut health will be determined by measuring plasma markers of gut barrier function before and after supplementation, as well as post-operatively.
* Aim 3 Reduction of post-operative inflammatory signaling will be measured with blood samples. Plasma cytokine levels, immune cell profiles, and inflammatory gene activation with an RNA hybridization panel will be measured pre-operatively and post-operatively.

Eligibility Criteria:
Inclusion Criteria:

* Infants and Children undergoing cardiac surgery with cardiopulmonary bypass

Exclusion Criteria:

* Antibiotics, surgery, or chemotherapy within the past 8 weeks
* Continuous enteral feeds before surgery
* GI pathology or intestinal surgery (excluding G-tube)
* Liver disease with elevated transaminitis or dialysis-dependent renal disease
Evaluation of the Effects of Immune Cells on Periodontal Healing

Periodontitis is an inflammatory disease with an infectious character, where, as the result of the host response to a dysbiotic microflora, attachment and bone loss occur. The host response and the healing period following the treatment differs among individuals, but the reason behind is not fully understood. The macrophages and T cells play an important role in the immune response and in the pathogenesis of periodontal diseases, but their role in the healing following periodontal therapy is not known. In this study, we aim to reveal the effects of initial macrophage and T cell activities in the gingival tissue on the differences of the response to phase I periodontal treatment.

42 individuals will be included in the study. Granulation tissue samples will be collected from two separate deep pockets of each individual, initially. At the same session, full-mouth scaling and root debridement will be conducted. Saliva, subgingival biofilm and gingival crevicular fluid (GCF) samples will also be collected, initially, and at the 2nd, 6th, 12th and 24th weeks. At the same appointments, periodontal parameters will be recorded. When the clinical procedures are concluded, the samples will be sent to Turku University with dry ice. Tissue and GCF concentrations of related cytokines will be analyzed with Luminex. The density of macrophage types will be defined by immunoblot analysis of related markers. Macrophage subpopulations in tissues will be specified by proteomics. Likewise, quantities of periodontal pathogens will be evaluated with DNA isolation and next generation sequencing.


Eligibility Criteria:
Inclusion Criteria:

* moderate to severe periodontitis
* having at least two pockets ≥ 6 mm
* systemic healthy

Exclusion Criteria:

* received periodontal treatment prior to study
* received antibiotic or antiinflammatory drugs in the last 6 months
* pregnant or in lactation