cyrilzakka/clinical-trials huggingface dataset:
IKKb-matured, RNA-loaded Dendritic Cells for Metastasised Uveal Melanoma

A Phase I vaccination trial in patients suffering from recently diagnosed metastatic uveal melanoma not cureable with local therapy and needing systemic therapy. IKKb-matured Dendritic Cells loaded with autologous tumor-RNA + RNA coding for defined antigens and driver mutations will be added to a standard therapy chosen by the tumor board (either checkpoint blockade or chemotherapy).

Intravenous infusion of 7.5 to 30 mio DCIKKb at 9 vaccination time points (week 1, 3, 7, 13, 19, 25, 31, 37 and 42) and in intervals of 2, 4, and 6 intervals of 6 weeks) is scheduled; the first 4 patients will receive reduced doses for the first 4 vaccinations, namely 7.5 mio (1st and 2nd vaccination) and 15 mio (3rd and 4th vaccination) DC followed by the full dose of 30 mio for subsequent vaccinations. Patients number 5 to 8 will receive initially reduced doses of 15 mio (1st and 2nd vaccination) DC for the first 2 vaccinations, and the full dose of 30 mio for subsequent vaccinations. Patients number 8 to 12 will receive the full dose of 30 mio cells from vaccination 1 onwards provided that no major side effects occurred. Patients will be vaccinated in a staggered approach by selectively decelerating release of the vaccine.

DCIKKb = autologous, monocyte-derived DC that are matured with the standard cocktail (TNF-alpha, IL-1 beta, IL-6 and PGE2) and IKKb-RNA loaded by electroporation with 1) autologous PCR-amplified total tumor mRNA, 2) RNA coding for defined tumor associated antigens (TAA) namely gp100, tyrosinase, PRAME, MAGE-A3, IDO) and 3) RNA coding for driver mutations (GNAQ/GNA11Q209 or R183, or the less frequently occurring SF3B1R625, CYSLTR2L129Q or PLCB4D630) by electroporation; RNAs for selected TAAs are in stock and will be transfected into the DCs only if expressed in the individual tumor of a patient (shown by RNA sequencing of the tumor); RNAs for selected driver mutations are in stock and will be loaded into the DCs only if the respective mutation is found (proven by exome and RNA sequencing) in the individual tumor.

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed unresectable stage IV metastatic uveal melanoma as per AJCC staging system 2014, 7th edition (updated 2018) not curable with local therapy modalities
* WHO performance status of 0, 1 or 2
* age from 18 and ≤ 75 years
* negative pregnancy test
* signed informed consent

Exclusion Criteria:

* Major serious illness
* evidence for HIV-1, HIV-2, HTLV-1, HBV or HCV infection
* active autoimmune disease requiring immunosuppressive therapy
* splenectomy or radiation therapy of the spleen
* organ allografts
* pregnancy
* lactation
* psychiatric disorders
* severe organic brain syndrome
A First in Human Study to Evaluate Safety, Tolerability, and Pharmacology of PF-06826647 in Healthy Subjects and Subjects With Plaque Psoriasis

This first in human study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06826647 in healthy subjects and subjects with plaque psoriasis.


Eligibility Criteria:
Healthy Participants:

Inclusion Criteria:

* Healthy male subjects between ages of 18-55 years
* Healthy female subjects of non-childbearing potential between the ages of 18-55 years
* Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight \>50kg (110lbs).
* No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
* (Optional) Japanese subjects who have four Japanese biologic grandparents born in Japan

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
* Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
* Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product
* Have a clinically significant infection currently or within 6 months of first dose of study drug

Psoriasis Participants:

Inclusion Criteria:

* Healthy male subjects between ages of 18-65 years
* Healthy female subjects of non-childbearing potential between the ages of 18-65 years
* Have a diagnosis of plaque psoriasis for at least 6 months prior to first study dose
* Have plaque-type psoriasis covering at least 15% of total body surface area (BSA) at Day-1(prior to randomization in the study
* No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)

Exclusion Criteria:

* Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis
* Have a clinically significant infection currently or within 6 months of first dose of study drug, or a history of chronic or recurrent infectious disease
* Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential
* Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product
Effect of Adding Modified Ketogenic Diet to Exercise Program in Treating Obese Patient With Multiple Sclerosis: A Randomized Controlled Trial

this study will be conducted to investigate the effect of adding Modified Ketogenic diet to exercise program in treating obese patient with multiple sclerosis.

Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain.Ketogenic diets (KDs) are high-fat, low-carbohydrate diets that mimic a fasting state. KDs create a metabolic shift from glycolytic energy production toward oxidative phosphorylation energetics by using fatty acids as a primary source of energy. As these fatty acids undergo beta-oxidation, ketones are produced. This increase in oxidative phosphorylation coupled with ketone production modifies the tri carboxylic acid cycle to limit reactive oxygen species generation. In addition, ketone bodies transported across the blood-brain barrier up regulate antioxidant pathway genes (particularly via the Nrf2 pathway) and boost energy production in brain tissue.sixty-four subjects with MS, ranged from 18-50 years. will be selected randomly divided into two groups each group consists of thirty-two subjects; experimental group (modified ketogenic diet+ aerobic exercise) and control group (aerobic exercise).

Eligibility Criteria:
Inclusion Criteria:

* Confirmed MS based on McDonald Criteria.
* Patients had to be fully ambulatory, not requiring assistive devices.
* The ages of 18 and 50
* Patients Body mass index (BMI) less than 30 Kg/m2.

Exclusion Criteria:

* Evidence of active disease or relapse phase within the last 30 days
* Chronic heart failure, cancer, chronic kidney disease, infection with human Immunodeficiency
* Addiction to drugs or alcohol.
* Pregnancy and Diabetic patient.
Compare Continuing Lamivudine Plus Adefovir or Adefovir Versus Switching to Entecavir Plus Adefovir in Patients With LAM-resistant Chronic Hepatitis B

The purpose of this study is to compare efficacy and safety of continuing Lamivudine plus Adefovir or Adefovir versus switching to Entecavir plus Adefovir in patients with LAM-resistant chronic hepatitis B who have suboptimal response to Lamivudine plus Adefovir or Adefovir


Eligibility Criteria:
Inclusion Criteria:

* Chronic hepatitis B
* Age ≥ 20 year old
* Currently taking Lamivudine and Adefovir combination therapy or Adefovir monotherapy for chronic HBV infection for 24 weeks
* Proven Lamivudine resistant mutation
* HBV DNA levels at screening ≥ 15 IU/mL
* Females must be post-menopausal, unable to conceive, or test negative for pregnancy via urine test
* Patient is able to give written informed consent prior to study start and to comply with the study requirements

Exclusion Criteria:

* A history or current of decompensated cirrhosis or hepatocellular carcinoma
* Currently receiving antiviral, immunomodulatory, cytotoxic or corticosteroid therapy
* Co-infected with HCV or HIV
* A history of organ transplantation
* Pregnant or breast-feeding
* Current clinically relevant of abuse of alcohol or drugs.
* Significant immunocompromised, gastrointestinal, renal(serum creatinine ≥ 1.5 mg/dL), hematological, psychiatric, bronchopulmonary, biliary diseases excluding asymptomatic GB stone, neurological, cardiac, oncologic, allergic disease or medical illness that in the investigator's opinion might interfere with therapy
* malignancy in previous 5 years
Low Dialysate Temperature During SLED

Objectives: This study is evaluating the hemodynamic effects of lowering the dialysate temperature in acute kidney injury (AKI) patients submitted to sustained low efficiency dialysis (SLED) in a single large center.

Methods: Participants will be randomly assigned to two treatment groups. One group will be started treatment with low temperature (set point 5 on the machine which is around 35°C) for one treatment and then alternate between high and low temperatures for a maximum of 8 treatments. The other group will be started with high temperature (set point 9 on the machine which is around 37°C) for the first treatment then alternate between high and low temperatures for a maximum of 8 treatments. Each participants will need at least two treatments, one with each temperature to be included in the analysis. The investigators will be looking for the number of events during a SLED treatment. Events will be defined as drop in systolic blood pressure ≥ 20 mmHg or drop in mean arterial pressure (MAP) of ≥10 mmHg, requirement of resuscitation with IVF after initiation of SLED, initiation or increase requirement of vasoactive drugs.


Eligibility Criteria:
Inclusion Criteria:

* 18 years of age or older, AKI stage 3 requiring RRT, maximum two pressers, initial temperature of 36°C or higher.

Exclusion Criteria:

* Initial temperature less than 36°C, ESRD, three or more pressers, requirement of antihypertensive medications.
Anal Canal Functional Assessment Using EndoFLIP

Faecal incontinence (FI) is characterized by involuntary loss of rectal content through the anal canal. FI is psychologically and socially debilitating problem that can dramatically affect patient's quality of life, often in otherwise healthy individual. FI can occur as a result of obstetric sphincter injury, surgery, irradiation, anorectal malformations as well as neurological, connective tissue or endocrine disorders. Currently management options for these patients are limited, partly due to the fact that control of defaecation and continence is multifactorial but also due to the fact that FI is difficult to identify the exact cause of patients' incontinence.

Current assessment of patients with FI include endoscopic assessment to rule out intraluminal organic cause for patients' symptoms, endoanal ultrasound scan / MRI to assess their pelvic floor anatomy and anorectal manometry to assess anorectal function. Anorectal manometry is a simple test to perform but Anorectal manometry is susceptible to measurement artifacts, with a high inter-individual variation with significant overlap between healthy asymptomatic and symptomatic patients with FI. Harris et al in 1966 suggested that the anal sphincter's resistance to distension that may be of importance for sphincter competence, not how tight anal sphincter can squeeze.

Endoluminal Functional Lumen Imaging Probe (EndoFLIP©) is a novel technology used to measure the dimensions and function of a hollow organ. Limited publication so far has shown that EndoFLIP© provides a new way of assessing anal sphincter competence. The study is to assess the use of EndoFLIP© to assess anal sphincter function in Hong Kong population. Firstly to evaluate whether age has an effect on the distensibility of the anal sphincter and its function and secondly to compare between symptomatic patients with faecal incontinence and asymptomatic healthy subjects.


Eligibility Criteria:
For Asymptomatic Group:

Inclusion Criteria: adults over 30 with no history of faecal incontinence, who are able to give consent.

Exclusion Criteria: Patients with history of gastrointestinal disease on medication or neurological disorder with bowel symptoms, anorectal surgery or previous bowel resection. Patients who are not willing to undergo the specified tests in this study. Pregnant women.

For Faecally Incontinent Group:

Inclusion Criteria: Adults over 30 with history of faecal incontinence for over 3months, who are able to give consent.

Exclusion Criteria: Patients who are not willing to undergo the specified tests in this study. Pregnant women and patients who has had anorectal surgery or bowel resection.
Assessment of Weber Humeral Derotational Osteotomy Using CT Scan

Subjects who have had the Weber osteotomy for Hill-Sachs lesions will have CT of Both shoulders. Amount of rotation in operative shoulder will be compared to contralateral. QOL will be assessed


Eligibility Criteria:
Inclusion Criteria:

* Subjects who have had the Weber osteotomy
Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis

The purpose of this study is to compare the efficacy and safety of isavuconazole versus voriconazole in the treatment of patients with invasive aspergillosis.

Acute invasive fungal infections caused by aspergillus, zygomycetes and other filamentous fungi remain life threatening diseases. Early treatment with highly effective anti-fungals reduces mortality. This study investigates the efficacy and safety of isavuconazole in the treatment of invasive fungal diseases, caused by Aspergillus or other filamentous fungi.

Eligibility Criteria:
Inclusion Criteria:

* Patients must have proven, probable or possible invasive fungal disease caused by Aspergillus species or other filamentous fungi
* Female patients must be non-lactating and at no risk for pregnancy

Exclusion Criteria:

* Patients with invasive fungal infections other than Aspergillus species or other filamentous fungi
* Evidence of hepatic dysfunction at Baseline or moderate to severe renal dysfunction
* Patients with chronic aspergillosis, or aspergilloma or allergic bronchopulmonary aspergillosis
* Patients who have received more than 4 days of systemic antifungal therapy other than fluconazole within the 7 days prior to the first administration of study medication
* Patients previously enrolled in a Phase III study with isavuconazole
* Patients with a body weight \</= 40 kg
Efficacy and Safety of Passiflora Incarnata and Isoflavona Combination in the Treatment of Climacteric Symptoms

The purpose of this study is to evaluate the effects of Passiflora incarnata and Isoflavone combination in relieving the symptoms associated with Climacteric Syndrome.

It is known that Hormone Therapy is recommended postmenopausal women to reduce menopausal symptoms and prevent osteoporosis frames and cardiovascular disease. However, only 30 to 40% of women still using hormone therapy.

One reason women do not continue or are reluctant to start Hormone Therapy is realizing that the prescription of hormones is not a natural situation. Therefore, there is an increased interest in the use and prescription of estrogen derived from plants, known as fitoestrogênios.

The development of a drug containing two standardized extracts was focused on two main symptoms of menopause: hot flashes and anxiety. This product comes from a longing for the doctors themselves can respond more promptly to patients who reach menopause and who already has a framework for mild to moderate anxiety.

Thus, to meet the woman who develops menopausal symptoms and that these two are highly prevalent during menopause, causing intense discomfort routine for this woman, was produced in association with Soy Passiflora aiming to control anxiety and hot flushes

Eligibility Criteria:
Inclusion Criteria:

* Female amenorrheic for at least one (1) year or surgical menopause since dosage of FSH ≥ 30 mIU / ml;
* Age greater than or equal to 40 and less than or equal to 65 years;
* Cytological examination colpo held at screening visit, Pap cytology classification with class I and II;
* By mammography BI-RADS classification (fourth edition) rated one (1) or two (2) performed at least six (6) months from the time of inclusion in the screening visit or if the research subject does not present a recent survey ;
* Line endometrial ≤ 8 mm by transvaginal ultrasound, performed at screening visit, in the case of subjects who have an intact uterus;

Exclusion Criteria:

* History of severe liver or renal disease at the discretion of the investigator;
* Hypertension stage III uncontrolled (SBP ≥ 180 mmHg or DBP ≥ 110 mmHg);
* Important cardiovascular disease such as coronary insufficiency or dilated cardiomyopathy advanced;
* Using estrogens, progestins, steroid or hormone replacement therapy (HRT) in the last 3 months;
* Estrogen-dependent neoplasia;
* Thromboembolic disorders for less than one year of screening visit;
* Anabolic drugs use or illicit drug use;
* Hemoglobin \< 10 or \> 17 g / dL;
* TSH \< 0, 550 or \> 4, 780 UUI / L;
* FT4 \< 0.75 ηg / dL or \> 1.8 ηg / dL;
* Patient that is chronically using MAO inhibitors (MAOIs) or levothyroxine
Oxidative Stress in Obstructive Sleep Apnea: Correlation of Biomarkers and Nasal CPAP Compliance

The purpose of this study is to check blood and urine levels to further define markers/tests in the blood and urine that would be useful in following patients with obstructive sleep apnea and then to see if by wearing CPAP every night, these markers can be reduced. This research is being done because currently there are no effective blood or urine markers to determine how well CPAP is working.

The goal of this study is to further define biomarkers that would be useful in following patients with obstructive sleep apnea and examining their response to compliance to therapy with CPAP. To date no correlation between biomarkers of oxidative stress and compliance to CPAP has been measured. CPAP is the most effective treatment for obstructive sleep apnea and has been show to reduce blood pressure and decrease oxidative stress.

Eligibility Criteria:
Inclusion Criteria:

* Men and Women over 18 years suspected of having sleep apnea

Exclusion Criteria:

* Those under 18 years or not suspected of having sleep apnea
Pharmacologic Intervention for Postcessation Weight Gain

To test pharmacologic intervention for smoking postcessation weight gain using nicotine gum and phenylpropanolamine (PPA).

BACKGROUND:

Despite the potential importance of weight gain to smoking relapse, in 1991 there had been virtually no success in eliminating, or even reducing, the weight gain following smoking cessation. Two promising pharmacologic methods for reducing postcessation weight gain were nicotine gum and an over-the-counter drug, phenylpropanolamine gum (\[PPA\]. However, the relative efficacy of these two drugs had never been evaluated and the mechanisms of action of both drugs on weight gain were unknown.

DESIGN NARRATIVE:

The investigators determined the efficacy of nicotine gum and phenylpropanolamine (PPA) gum relative to a placebo in the reduction of postcessation weight gain throughout a 13-week combined behavioral and pharmacologic treatment program. Following cessation of the drugs at the end of treatment, they monitored long-term effects of these drugs on body weight at both a 6- and a 12-month follow-up. They also determined the mechanism of action of both nicotine gum and PPA gum (viz., changes in dietary intake, physical activity, or metabolic rate) on change in weight during the course of treatment and evaluated withdrawal symptoms of smoking cessation as they were moderated by either nicotine gum or PPA gum use during the course of treatment. Finally, they investigated whether PPA and nicotine gum produced an incremental effect on smoking cessation (relative to placebo gum) in a sample of female smokers who were at high risk for postcessation weight gain at posttest and at a 6- and 12-month follow-up.

Eligibility Criteria:
No eligibility criteria
Foot and Ankle Range of Motion (Stretching) Apparatus

Range of motion at ankle joint and subtalar joint will be assessed before and after utilization of ARM device. The changes in range of motion will be recorded and compared to literature.

The purpose of this study is to assess how effective a new device is in increasing range of motion and reducing stiffness in the foot and ankle of patients with acquired flatfoot, patients with plantar fasciitis, and those suffering from stiffness after cast removal or other lengthy immobilization.

Project will utilize a physical therapist to measure range of motion and stiffness when patients are consented. Patients will be re-measured at six weeks following use of the device to assist in stretching ankle and foot muscles, and again at 10 weeks for final stiffness and range of motion assessment.

Eligibility Criteria:
Inclusion Criteria:

* 18 years of age or older
* stiffness in or about the ankle joint due to age, diabetes, trauma, flatfoot, plantar fasciitis, or immobilization

Exclusion Criteria:

* not physically able to use device
* patients with pain disorders
* patients lacking necessary hand-eye coordination
* patients using lower extremity external fixator
* patients with history of non-compliance
24 Month Extension to Efficacy and Safety of AEB071 Plus Tacrolimus (Converted to Mycophenolic Acid After 3 Months) in Renal Transplant Patients(Converted to Mycophenolic Acid After 3 Months) in Renal Transplant Patients

This study will provide continued treatment and assess the long term safety, efficacy and tolerability of oral AEB071 plus tacrolimus vs. mycophenolic acid plus tacrolimus after kidney transplantation.


Eligibility Criteria:
Inclusion criteria:

* Participation in core study CAEB071A2203
* The patient has been maintained on AEB071/mycophenolic acid or tacrolimus/mycophenolic acid, consistent with their original randomization, at their core study Month 12 visit.
* Women capable of becoming pregnant are required to practice a medically approved method of birth control as long as they are on study medication and for a period of 3 months following discontinuation of study drug(s).

Exclusion criteria:

* Pregnancy. Other protocol-defined inclusion/exclusion criteria may apply