cyrilzakka/clinical-trials huggingface dataset:
A Single Dose Safety, Tolerability, Pharmacokinetic and Food Effect Study of KVD900 (Sebetralstat) in Healthy Volunteers

A safety, tolerability, pharmacokinetic and food effect study of KVD900 in healthy volunteers.


Eligibility Criteria:
Inclusion Criteria:

* Healthy male subjects between 18 and 55 years of age.
* Healthy subjects as determined by past medical history and as judged by the Chief Investigator or designee.
* Male subject willing to use a highly effective method of contraception.
* Subject with a body mass index (BMI) of 18-32 kg/m2.
* Subject with no clinically significant history of previous allergy or sensitivity to KVD900 or any of the excipients contained within the investigational medicinal product (IMP).
* Subject with no clinically significant abnormal serum biochemistry, haematology, clotting profiles, and urine examination values within 28 days before the first dose of IMP.
* Subject with a negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP
* Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
* Subject with no clinically significant abnormalities in 12-lead electrocardiogram
* Subjects must not donate sperm from first dose until at least 3 months after last dose of IMP.
* Subjects without any special food restrictions that would hinder ability to consume the high fat breakfast provided during study Part C; such as lactose intolerance , vegan, low-fat, low sodium, etc.
* Subjects with no known allergy or sensitivity to lactose and/or any additional excipients contained in IMP.
* Subject must be available to complete the study (including all follow up visits).
* Subject must satisfy the Chief Investigator or designee about their fitness to participate in the study.
* Subject must provide written informed consent to participate in the study.

Exclusion Criteria:

* A clinically significant history of gastrointestinal disorder likely to influence IMP absorption.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements .
* Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular (no history of syncope or vasovagal events), or metabolic dysfunction.
* Subjects with a history of clotting abnormalities.
* A clinically significant history of drug or alcohol abuse in the last 5 years.
* Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements.
* Inability to communicate well with Investigators.
* Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP.
* Donation of 450 mL or more blood within the 3 months before the first dose of IMP.
Efficacy and Safety of the Combination of Anlotinib and JS001 in EGFR-TKI Resistant T790M-Negative NSCLC

This study is designed to evaluate the efficacy and safety of the combination of Anlotinb and JS001 in EGFR-TKI resistant T790M-negative NSCLC patients.

All EGFR mutation NSCLC patients with EGFR-TKIs eventually develop acquired resistance and in 40%-50% of these the resistance mechanism is based on the EGFR T790M mutation who could receive Osimertinib. Several alternative mechanisms of escape from EGFR-TKIs have been detected in NSCLC patients without the T790M, such as Met application, BRAF mutation, PIK3CA mutation, etc, who could receive the combination of EGFR-TKI with comparable target drug. Given the lack of targeted therapy for the majority of T790M-negative patients, platinum-doublet chemotherapy remains the standard of care with low effectiveness. In the present study, we aimed to evaluate the efficacy and safety of the combination of Anlotinb and JS001 in EGFR-TKI resistant T790M-negative NSCLC patients.

Eligibility Criteria:
Inclusion Criteria:

* Adult patients \>=18 years of age
* Inoperable locally advanced, recurrent, and/or metastatic NSCLC patients with EGFR sensitive mutation
* EGFR-TKI resistent
* EGFR T790M negative
* Expected survival ≥ 3 month;
* ECOG / PS score: 0-2;
* the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL \<1.5 times the upper limit of normal (ULN); Liver ALT and AST \<2.5 × ULN and if liver metastases, ALT and AST \<5 × ULN; Serum Cr ≤ 1 × ULN, endogenous creatinine clearance ≥50ml/min

Exclusion Criteria:

* EGFR-T790M positive
* with druggable gene alteration;
* Patient can not comply with research program requirements or follow-up;
Effectiveness of Vitamin C Supplementation in Treatment of Rickets

Effectiveness of therapeutic dose of vitamin C in infants and children with nutritional rickets as an adjuvant therapy with vitamin D and calcium The study is two armed Randomized Control Trial, to validate the role of Vit C supplementation on bone turnover infants and children with nutritional rickets.

* Population of study \& disease condition The study will include 88 infants and children with nutritional rickets
* Study setting:

The patients will be recruited from out-patient clinic of Cairo University Children's Hospital.

- Inclusion criteria: Any infant or child between 6 months and 3 years with nutritional rickets

* Exclusion criteria:

  1. Unwilling to participate in the study.
  2. Non nutritional causes of rickets as hypoparathyroidism, renal causes, chronic liver disease, and malabsorption.
  3. Children on vitamin C supplements above Recommended Daily allowance
* Methodology in details:
* History including age, sex, onset of manifestations, nutritional history, family history of similar condition, history of tetany or convulsion, motor development, drug intake, fractures, history of dentition, and manifestations of vitamin C deficiency (musculoskeletal pain, irritability, loss of appetite, petechiae, ecchymosis, gingival bleeding, alopecia, and poor wound healing) will be taken.
* Examination including anthropometric measurements, limb deformities, anterior fontanelle, cranial sutures, teeth, and gingival mucosa.
* Serum measurements of calcium, phosphorous, alkaline phosphate, Parathyroid hormone, and 25 hydroxy-vitamin D will be done at first visit then follow up of serum calcium, phosphorous and alkaline phosphatase after 4 and 12 weeks after starting the treatment.
* Radiological investigation in the form of anterior view X-ray of the knee that reveals the metaphysis end and epiphysis of the femur and tibia will be done at first visit and follow up after 4 weeks.
* Serum level of post treatment N-MID-osteocalcin detection (marker of bone turnover) \[6\] by ELIZA , Catalogue number E1499Hu Bioassay technology la laboratory England/China

The patient will be randomized 1:1 by computer randomization sequence into two groups (A, B). All patients will receive therapeutic dose of vitamin D (either single-day dose of 600,000 U or daily doses of 5000 U for 2-3 months) and oral elemental calcium according to Recommended Daily allowance . However, group A will receive oral vitamin C (100 mg three times daily for one week then 100 mg once daily for 1-3 months) in addition to the above-mentioned treatment.

Eligibility Criteria:
Inclusion Criteria:

Clinical diagnosis:

* Nutritional rickets in infants or children between 6 months and 3 years.
* Normal liver and kidney functions.
* The parents must be compliant to the clinic visits and the treatment doses.

Exclusion Criteria:

* Unwilling to participate in the study.
* Non nutritional causes of rickets as hypoparathyroidism, renal causes, chronic liver disease, and malabsorption.
* Children on vitamin C supplements above RDA.
Pilot Study: Utilizing Manometry to Assess Radiation-Induced Changes in Esophageal Function

The purpose of this study is to prospectively assess the feasibility of high-resolution manometry to identify radiation-induced changes in esophageal motility and contractility or "function" in patients undergoing radiation therapy for the treatment of locally advanced lung cancer.

As there is no standard of care to evaluate/visualize the effects of radiation therapy (RT) -induced esophageal injury, this is routinely assessed by patient reported accounts, and the symptoms are then managed supportively (e.g. with pain medicines, parenteral nutrition, feeding tubes etc). Manometry has been frequently used to study the effects of RT on gastrointestinal function in the setting of numerous malignancies, including colorectal, cervical and prostate cancers. What is often seen after RT is decreased sphincter function in the anorectal region leading to problems with continence and fecal urgency, however there has not been as rigorous of an evaluation of esophageal function after RT.

One study performed more than 15 years ago included only 4 patients with lung cancer and concluded that mucosal irritation was likely the primary cause of RT-associated esophageal injury and no abnormalities in motility were seen. Radiation is known to cause long-term esophageal injury including stricture, and there is manometric evidence of impaired motility long-term after RT. The recent introduction of high-resolution manometry permits more extensive evaluation of the effects of RT on esophageal function.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years or older
* Absence of any severe disorders of esophageal motility (patients with reflux and/or a hiatal hernia are eligible)
* Histologically confirmed lung cancer scheduled to undergo conventionally fractionated radiation treatment
* Patients that will be treated with a minimum of 45 Gy of radiation therapy
* Patients with mediastinal nodal disease, or primary lesions that are near the esophagus are eligible provided that they are not having esophageal symptoms believed to be due to the tumor.

Exclusion Criteria:

* History of esophageal motility disorder that pre-dates and is unrelated to the present diagnosis of lung cancer
* History of any prior radiotherapy to the esophagus
* Pregnant or lactating women
* Inability to understand and follow swallowing instructions for the esophageal manometry procedure; this is to ensure patient compliance of performing the breath hold technique throughout the radiation therapy treatment
* Patients with mediastinal nodal disease, or primary lesions, that are having esophageal symptoms believed to be due to the tumor
Improving the Appearance of Skin and Hair in Patients Undergoing Valley Fever Treatment

This will be a multi-visit study that will take approximately 3 hours in total. Up to 200 subjects from the BUMC Valley Fever and BUMC Dermatology clinics will be enrolled in this study and assigned to one of three cohorts according to timeline of oral anti-fungal therapy. Subjects in Cohort 1 will be randomized to apply topical cholesterol-containing moisturizers to the skin, hair and lips on either the right or left side of the body daily. Measurements of skin barrier function, appearance of skin and hair, and hair samples will be obtained at baseline and at 4 week follow-up visits. Cohorts 2 and 3 will be observational groups at differing points in oral antifungal treatment regimen. Subjects will be randomized to have measurements of skin barrier function and hair and skin characteristics obtained from either the right or left side of the body at baseline and at monthly follow-up visits.

Coccidioidomycosis, also known as Valley Fever, is a fungal condition most commonly seen in Arizona and can affect multiple organs, including the skin, lung, bone, joints, and central nervous system. Oral antifungal therapy such as fluconazole is the first-line medication to treat coccidioidomycosis. Through the investigator's clinical observations at the Valley Fever Center for Excellence, nearly all patients who have been placed on systemic azole treatment show some extent of cosmetic changes in their skin and hair, such as dry skin, chapped lips, hair loss, and change in hair characteristics. The goals of the study are to 1) understand the cosmetic changes in the skin and hair in patients initiating and discontinuing long-term oral antifungals, and 2) to examine whether cholesterol-based commercially-available moisturizers for the skin and for the hair can improve the cosmetic appearance better than a vehicle without these cholesterol ingredients.

Eligibility Criteria:
Inclusion Criteria:

* Men and women, age 18 or older
* Patients who have been diagnosed with coccidioidomycosis (valley fever) requiring oral anti-fungal medications such as but not limited to fluconazoles
* Able to comprehend and read the English language

Exclusion Criteria:

* Subject does not fit inclusion criteria
* Children younger than 18 years of age
* Pregnant women
* Prisoners or those that are cognitively impaired
* Those with known allergies or intolerance to ingredients in the topical formulations
* Subject is unwilling or unable to comply with study procedures
* Unable to read or comprehend English
Attention Bias Modification Treatment (ABMT) for Anxiety Disorders in Youth

Attention biases in threat processing have been assigned a prominent role in the etiology and maintenance of anxiety disorders. Attention Bias Modification Treatment (ABMT) utilizes computer-based protocols to implicitly modify biased attentional patterns in anxious patients. This is a double-blind randomized controlled trial of ABMT for clinically anxious 10-18 year-olds. Participants will be assessed using clinical interviews and parent- and self-rated questionnaires before, in the middle and after twelve sessions of ABMT or control groups, and again at ten-week follow-up. Outcome measures will be anxiety symptoms and depression as measured by gold standard questionnaires as well as structured clinical interviews with youth and their parents. Attentional threat bias, Attentional control and interpretation of ambiguous information will also be measured to explore potential mediators of ABMT's effect on anxiety. The investigators expect the findings to inform pathways to treatments for anxious children and to provide initial information on mechanisms of ABMT efficacy.


Eligibility Criteria:
Inclusion Criteria:

* Primary diagnosis of GAD, SOP, or SAD.
* Co-morbid attention deficit hyperactivity disorder (ADHD) or depressive disorders must be treated with medication and stable.
* Tics or impulse control problems must be treated with medication, stable and cause minimal or no impairment.

Exclusion Criteria: To be excluded youth must:

* meet diagnostic criteria for Organic Mental Disorders, Psychotic Disorders, Pervasive Developmental Disorders, or Mental Retardation.
* show high likelihood of hurting themselves or others.
* have not been living with a primary caregiver who is legally able to give consent for the child's participation.
* be a victim of previously undisclosed abuse requiring investigation or ongoing supervision.
* be involved currently in another psycho-social treatment.
* have a serious vision problem that is not corrected with prescription lenses.
* have a physical disability that interferes with their ability to click a mouse button rapidly and repeatedly.
C7-T1 Epidural Steroid Injections Versus Targeted Injection for Treatment of Cervical Radicular Pain

Cervical radicular pain is a common, disabling problem, occurs in 83:100,000 individuals per year. Symptoms are most often caused by intervertebral disc herniation (21.9%) or central or foraminal stenosis from spondylosis (68.4%). Patients complain of pain in the head, neck, scapula or arm. The diagnosis of radicular pain is made clinically by history and physical examination, supported by imaging studies and electrodiagnostic tests. No study has compared the differences in pain, medication utilization, functional outcomes, or patient satisfaction between interlaminar and targeted epidural injections in the cervical spine. In theory, the technique of targeted epidural steroid delivery with a catheter has a lower risk of accidental vascular trespass or disc penetration during the procedure, and far less risk of dural penetration or spinal cord injury at rostral levels of the cervical spinal cord as compared with the interlaminar technique. The investigators hypothesize that this technique results in superior pain control, decreased medication use, improved function and fewer repeat injections. This data could improve patient safety and affect the evolving treatment guidelines for cervical epidural injections.

Cervical radicular pain is a common, painful, disabling problem, often treated by epidural steroid injection (ESI). Two techniques of steroid delivery into the cervical epidural space include the transforaminal and interlaminar approaches. We aimed to determine if the CIESI with versus without a catheter is associated with superior clinical outcomes at follow-up. We hypothesized that the use of a targeted epidural catheter technique would result in superior pain control, function, decreased analgesic use, and lower surgical incidence as compared to standard CIESI at C7-T1.

Eligibility Criteria:
Inclusion Criteria:

* All patients ages 18-75 with C2-6 unilateral radicular pain who are scheduled to undergo cervical epidural steroid injection treatment.
* Pain lasting greater than 2 weeks.
* Pain resistant to a trial of conservative therapy (i.e. oral steroids,nonsteroidal anti-inflammatory drugs, opioids, muscle relaxants, physical therapy or chiropractic care)

Exclusion Criteria:

* Patient refusal.
* Lack of consent.
* Systemic infection or local infection over planned injection site in posterior cervical spine.
* Bleeding disorder, current use of anticoagulants or anti-platelet medications.
* Intrinsic spinal cord lesions in the cervical region.
* History of central neurologic, cerebrovascular, demyelinating or muscular disease.
* Concomitant use of oral or injected steroids.
* Allergy to medications being used for injection procedures.
* Inability to communicate with staff or to participate in follow up.
* Pregnancy.
* Inability to perform handgrip or arm strength testing.
* Cognitive deficit or motor neuron disease.
* Daily opiate use that preceded the onset of cervical radicular symptoms or daily opiate use exceeding 3 months prior to study inclusion
Investigation of Pain Incidence After FK506 Immunosuppressive Therapy in Liver Transplantation Patients

FK506 (tacrolimus), a calcineurin inhibitor, is widely used as an immunosuppressant to lower the risk of organ rejection after organ transplantation, and to treat T cell-mediated diseases such as eczema and atopic dermatitis. FK506 treatment often accompanies pain sensation in patients with atopic dermatitis or after organ transplantation. In previous studies, the investigators confirmed that FK506 treatment increased neuronal activity of primary afferent neurons and causes pain behavior in naïve mice. In order to further search for objective clinical evidence, the investigators proposed to investigate pain incidence after FK506 immunosuppressive therapy in liver transplantation patients. The investigators will investigate pain incidence and pain intensity in patients who underwent liver transplant from September of 2011 to May of 2018 in the Liver Health Rehabilitation Association. The patients who were divided into two groups based on whether or not FK506 was used in the immunosuppressive therapy. The patients in control group (without FK506 treatment) and FK506-treated group report pain sensation 3 months and 12 months after liver transplant. The investigators will compare the pain incidence between the two groups at both time points. On the other hand, the investigators will further investigate changes in pain sensation after 1st and 2nd reductions of FK506 dose. Pain is reported subjectively by the patient using the visual analogue scale (VAS) 1 month after dose reduction. In our study, 1st and 2nd reductions of FK506 dose refers to the first two dose-adjustments (approximately 6 months apart) that occurred 3-6 months after the liver transplantation.


Eligibility Criteria:
Inclusion Criteria:

1. had liver transplantation for end-stage liver disease
2. was ≥18 years of age at the time of liver transplantation -

Exclusion Criteria:

1. liver cancer
2. acute (fulminant) liver failure
3. multiorgan transplant
4. chronic postsurgical pain
5. fibromyalgia, osteoarthritis, low back pain and inflammatory pain of any origin
6. peripheral and central neuropathic pain of any origin
7. chronic secondary visceral pain
8. chronic cancer-related pain that is due to cancer or its treatment -
Phase III Study of Chondrocyte Alginate Gel Suspension in Pediatric Patients With Vesicoureteral Reflux

OBJECTIVES: I. Determine the safety and efficacy of chondrocyte alginate gel suspension in pediatric patients with vesicoureteral reflux.

II. Determine the long term efficacy of this treatment regimen in this patient population.

III. Evaluate the short and long term avoidance of surgery or antibiotic therapy after this treatment regimen in this patient population.

IV. Estimate the risk:benefit ratio of this treatment regimen in these patients.

PROTOCOL OUTLINE: This is a multicenter study. Patients undergo biopsy of the auricular cartilage for chondrocytes during cystoscopic evaluation on day 1. Chondrocyte alginate gel suspension is injected into the submucosa of the bladder at the vesicoureteral junction between days 40-50. Patients found to have post treatment reflux may be retreated once.

Patients are followed at 1, 3, and 12 months.

Eligibility Criteria:
PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

* Confirmed grade 3 or 4 reflux in at least one ureter by voiding cystourethrogram Breakthrough urinary tract infection despite standard antibiotic therapy OR Persistent reflux unlikely to resolve spontaneously
* Grade 3: 2 year reflux duration OR 1 breakthrough infection Grade 4: 1 year reflux duration OR 1 breakthrough infection
* Coexisting grade 1 or 2 reflux OR Resolved reflux (i.e., contralateral to the existing grade 3 or 4 refluxing ureter) allowed
* No reflux secondary to obstruction or neuropathic disease
* No gross urological abnormalities (e.g., megaureter requiring ureteral tapering or duplicity of ureters)

--Prior/Concurrent Therapy--

* Surgery: No prior surgery for correction of reflux No recent prior urological device implantation

--Patient Characteristics--

* Hematopoietic: No history of bleeding disorders
* Cardiovascular: No history of hypertension or cardiac disease
* Pulmonary: No history of pulmonary disease
* Other: No known allergies to contrast dyes, iodine, or shellfish No contraindications to general anesthesia No prior infections (other than UTIs) No immunodeficiencies No metabolic disease No social situation that would interfere with follow up Not pregnant Negative pregnancy test
The Comparison of Desflurane and Sevoflurane on Postoperative Recovery and Hepatic Function of Biliary Atresia Patients During Kasai Operation

Biliary atresia (BA) is a perinatal disease of unclear etiology, characterized by inflammation and obliteration of intrahepatic and extrahepatic bile ducts, leading to cholestasis and cirrhosis. Kasai operation remains as the first line operative treatment in BA. In the previous studies, inhalation anesthetics might induce liver damage. The choice of inhalation anesthetic that minimally affects hepatic function is important. Therefore, the purpose of this study is to compare the postoperative recovery and hepatic function between desflurane and sevoflurane, two most frequently used inhalational anesthetics in patients undergoing Kasai operation.


Eligibility Criteria:
Inclusion Criteria:

* patients with biliary atresia undergoing Kasai operation

Exclusion Criteria:

* patients with congenital anomalies at major organs