araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Developing and Implementing Familial Hypercholesterolemia Registry

Summary: Familial hypercholesterolemia (FH) is a most prevalent genetic disorder define as high cholesterol level and premature death. The prevalence of FH reported in few countries however unknown in Iran. Thus determine the FH patient, finding diagnostic strategy and appropriate treatment are important. We intent to use cascade method to screening patients, also our expected outputs are to develop and implement a registry program for FH patients and their families and to study their genetic disorder. FH patients will be followed from management, treatment and prevention of Cardio vascular disease in order to increase premature death.

Detailed description: Familial hypercholesterolemia (FH) is a genetic disorder define as high cholesterol levels, particularly very high levels of low-density lipoprotein (LDL), in the blood and early cardiovascular disease and premature death. FH is an autosomal dominant disease with a prevalence 1:500 (new study in Netherlands demonstrated 1:244) in population more frequent than Cystic fibrosis, mellitus diabetes or neonatal hypothyroidism. Canadian registry demonstrated FH is more common among people if French Canadian, Christian Lebanese, and Afrikaner descent. The Major causes of FH are pathogenic variant in the LDL-receptor (LDLR) gene or the Apo lipoprotein B (APOB) gene. The clinical signs of FH are high level of Cholesterol (between 350-550 mg/dL in heterozygous), Yellow deposits of cholesterol-rich fat in various places on the body such as around the eyelids (known as xanthelasma palpebrarum), the outer margin of the iris (known as arcus senilis corneae), and in the tendons of the hands, elbows, knees and feet, particularly the Achilles tendon (known as a tendon xanthoma). FH is a hidden syndrome which leads to cardiovascular disease.
  After introducing the statins total mortality have reduced significantly in these patients. Thus screening and identification of patients and treatment with the most effective therapies will decrease the risk of premature death.
  Also, most of patients require an appropriate lipid-lowering medications. Although the genetic problem is the most important factor to expression of FH other factors like environmental and metabolic factor can be effective in CVD and premature death.
  Therefore, identification and follow-up FH patients is important for CVD Rate cuts and decrease Treatment costs thus this study can gain these outcomes.

Eligibility: Inclusion Criteria:
  Personal concentration of LDL-C > 190 mg/dL or LDL-C > 120 mg/dL in Treatment Group.
  Family and/or personal history of premature heart disease.
  Exclusion Criteria:
  Hyperlipidemia with underlying disorders.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Prevalence Assessment and Characterization of Psychological Disorders Associated With Hypobetalipoproteinemia

Summary: Familial hypobetalipoproteinemia (FHBL, OMIM # 1707730) is a genetic disorder heterozygotic of LDL-C metabolism. Clinical manifestation range from asymptomatic patients to metabolic (fatty liver, diabetes) or psychiatric disorders still unrecognized. HYPOPSY research, aims to evaluate prevalence of hypobetalipoproteinemia, and to characterize specific related psychiatric disorders.

Detailed description: Familial hypobetalipoproteinemia (FHBL, OMIM # 1707730) is a genetic disorder heterozygotic of LDL-C metabolism (Low Density Lipoprotein - Cholesterol) whose incidence is measured from 1: 500 to 1: 1000. These heterozygous individuals may be asymptomatic or present some clinical (fatty liver, diabetes) or psychiatric manifestations still unrecognized. Moreover, these individuals have mostly a longevity syndrome and cardiovascular protection. The FHBL is often due to mutations of the APOB (APOlipoprotein B), major component of LDL, VLDL (Very Low Density Lipoprotein) and chylomicrons, and in some cases, loss-of-function mutations of the serine protease PCSK9, endogenous inhibitor of the LDL receptor.
  HYPOPSY research, aims to evaluate, in a population with psychiatric disorders, the prevalence of hypobetalipoproteinemia, and to characterize specific related psychiatric disorders.

Eligibility: Inclusion Criteria:
  -  Patients admitted in mental Disorders Unit in Nantes University Hospital
  Exclusion Criteria:
  -  Minor patient

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Efficacy And Safety Of Bococizumab For Lipid Lowering In Asian Hypercholesterolemia Subjects

Summary: This study is a Phase 3, double blind, placebo controlled, randomized, stratified, parallel group, multi-center clinical trial designed to compare the efficacy and safety of bococizumab 150 mg SC Q2wks to placebo for LDL-C lowering in subjects with primary hyperlipidemia or mixed dyslipidemia at high or very high risk for CV events. The study will enroll a total of approximately 750 subjects from 4 - 5 Asian countries/areas (including China mainland); of which approximately 600 subjects will be from sites in China. Subjects will be randomized into a bococizumab treatment arm and a placebo arm in a 1:1 ratio.

Detailed description: After providing consent, subjects will enter a screening period of approximately 28 days to verify eligibility for the trial. Eligible subjects will be considered enrolled and progress to the Randomization visit. Results from screening evaluations will be reviewed and only subjects who continue to meet all eligibility criteria will be randomized. Randomized subjects will enter the 12-week treatment period, followed by a 40-week long-term treatment period and a 6 week follow-up, for a total of 58 weeks (approximately 14 months) study participation. Subjects will attend clinic visits as shown in the Schedule of Activities. Subjects will be randomized to receive either 150 mg Q2wks of bococizumab or placebo in a 1:1 ratio. Lipid levels will be blinded to the investigator and staff, subject and sponsor.

Eligibility: Inclusion Criteria:
  -  Males and females at the age or over 18 years of age.
  -  With primary hyperlipidemia or mixed dyslipidemia.
  -  Treated with stable daily dose of statins
  -  At high or very high risk of incurring a CV event
  -  Fasting LDL-C >=70 mg/dL (1.81 mmol/L) for subjects on the highest approved dose of statins; Fasting LDL C >=77 mg/dL (1.99 mmol/L) for subjects not on highest approved dose.
  -  Fasting TG ≤400 mg/dL (4.51 mmol/L)
  Exclusion Criteria:
  -  Prior exposure to bococizumab or other investigational PCSK9 inhibitor
  -  NYHA class IV, or Left Ventricular Ejection Fraction <25%
  -  Poorly controlled hypertension
  -  History of hemorrhagic stroke or lacunar infarction resulting in a stroke
  -  Untreated hyperthyroidism or TSH >1 × ULN
  -  Undergoing apheresis or have planned start of apheresis.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

Summary: The purpose of this study is to assess the safety, tolerability, and efficacy of ALN-PCSSC in participants with homozygous familial hypercholesterolemia.


Eligibility: Inclusion Criteria:
  -  Males and females, ≥12 years of age with a diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated low-density lipoprotein cholesterol (LDL-C) concentration >500 mg/deciliter (dL) [13 millimoles/liter (mmol/L)] together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents.
  -  Stable on a low-fat diet.
  -  Stable on pre-existing, lipid-lowering therapies (such as statins, cholesterolabsorption inhibitors, bile-acid sequestrants, or combinations thereof) for at least 4 weeks with no planned medication or dose change for the duration of study participation.
  -  Fasting central lab LDL-C concentration >130 mg/dL (3.4 mmol/L) and triglyceride concentration <400 mg/dL (4.5 mmol/L).
  -  Body weight of 40 kilograms (kg) or greater at screening.
  Exclusion Criteria:
  -  LDL or plasma apheresis within 8 weeks prior to the screening visit, and no plan to receive it during the study because of the attendant difficulty in maintaining stable concentrations of LDL-C while receiving apheresis.
  -  Use of mipomersen or lomitapide therapy within 5 months of screening.
  -  Previous treatment with monoclonal antibodies directed towards PCSK9 within 8 weeks of screening.
  The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: To Assess the Safety, Efficacy and Tolerability of CKD-519, Administered With HMG-CoA Reductase Inhibitors

Summary: A multicenter, double-blind, parallel-group, active-controlled, dose-ranging study to assess the safety and efficacy of the novel cholesteryl ester transfer protein (CETP) inhibitor CKD-519 in combination with atorvastatin or rosuvastatin in subjects with dyslipidemia.

Detailed description: The purpose of this study is to assess the safety, efficacy, and tolerability of CKD-519, administered with HMG-CoA reductase inhibitors in subjects with dyslipidemia

Eligibility: Inclusion Criteria:
  1. Age 18 to 80 years.
  2. Dyslipidemia with LDL-C
  -  At screening if untreated: 100 to 190 mg/dL
  -  At screening if treated with statins or other lipid-lowering drugs: 100 to 170 mg/dL
  -  At start of double-blind treatment: 100 to 190 mg/dL.
  3. HDL-C <45 mg/dL (males) or <50 mg/dL (females).
  4. Fasting TG <400 mg/dL.
  5. Presence of the following conditions is permitted but not mandatory, at the discretion of the investigator:
  -  Treated and stable coronary heart disease without acute events in the past 3 months and stable, state-of-the-art medication.
  -  Treated and stable carotid artery disease or peripheral arterial disease on stable, standard medication for the past 3 months
  -  Treated and stable Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) ≤9.5%.
  6. Willing and able to sign the informed consent form (ICF).
  Exclusion Criteria:
  1. Chronic heart failure as defined by New York Heart Association classes III and IV.
  2. Uncontrolled cardiac arrhythmias.
  3. Myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or unstable angina in past 3 months before Visit 1.
  4. Stroke or transient ischemic attack within 3 months before Visit 1.
  5. Uncontrolled hypertension.
  6. Clinically significant laboratory abnormalities
  -  Aspartate aminotransferase or alanine aminotransferase >2 times upper limit of normal range
  -  Bilirubin >1.5 times upper limit of normal range
  -  Creatine kinase >2 times upper limit of normal range.
  7. Any active nephropathy or estimated glomerular filtration rate <60 mL/min/1.73m2 or on kidney dialysis.
  8. Poorly controlled (thyroid-stimulating hormone [TSH] >2 times upper limit of normal) hyperthyroidism.
  9. Homozygous familial hypercholesterolemia.
  10. Intolerance or hypersensitivity to atorvastatin or rosuvastatin.
  11. Prior treatment with any CETP inhibitor.
  12. Positive for human immunodeficiency virus (HIV) positive, hepatitis B or hepatitis C.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: PCSK9 Inhibitors in the Progression of Aortic Stenosis

Summary: Investigators plan evaluate whether PCSK9 inhibitors, a medication that can lower lipoprotein(a) and control dyslipidemia, can inhibit the progression of aortic stenosis, through a randomized controlled trial.

Detailed description: Aortic valve disease is the most common form of heart valve disease and is a major burden to society. Aortic valve disease is also expected to become more prevalent with the aging. Among aortic diseases, 'aortic stenosis (AS)', which is a narrowing of the aortic valve, and leads to symptoms of heart failure and sometimes death.
  For treatment of AS, the valve in replaced in a surgical to percutaneous method. Regardless of the method, valve replacement has its potential costs and complications that is an important issue that needs to be solved. Therefore, controlling the progression of AS and increasing the efficacy of medical therapy before valvular replacement is needed, is an important medico-social problem.
  Regarding the pathophysiology of AS, an elevation of lipoprotein(a) and dyslipidemia have been reported to be associated with the progression of cardiovascular calcification.
  PCSK9 inhibitors, which is a medication that can control both lipoprotein(a) and dyslipidemia may be a effective medication to control the progression of AS.
  Therefore, investigators will perform a randomized control trial, to compare the effect of PCSK9 inhibitors vs. placebo in its influence to AS progression.

Eligibility: Inclusion Criteria:
  1. The patient agrees to participate in this study by signing the informed consent form. Alternatively, a legally authorized patient representative may agree to the patient's participation in this study and sign the informed consent form.
  2. The patient has a working diagnosis of aortic stenosis (mild to moderate), and has fair treatment compliance.
  Exclusion Criteria:
  1. Age under 19 years old
  2. Hypersensitivity to PCSK9 inhibitor
  3. LDL cholesterol < 70mg/dL at baseline
  4. Poor treatement compliance (The patient will need to visit the out-patient clinic every 2-weeks for medication)
  5. Positive pregnancy test or is known to be pregnant
  6. Any other reason the investigator deems the subject to be unsuitable for the study (e.g., Active malignant tumor, Any life-threatening condition with life expectancy less than 6months, etc.)
  7. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the investigator, would preclude safe completion of the study

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Expanded Access to Entrectinib for Cancers With NTRK1/2/3, ROS1, or ALK Gene Fusions

Summary: Expanded access to entrectinib will be given to patients with cancers harboring NTRK1/2/3, ROS1, or ALK gene fusions who do not qualify for participation in, or who are otherwise unable to access, an ongoing clinical trial for entrectinib.


Eligibility: Inclusion Criteria:
  -  Diagnosis of advanced cancer with an NTRK1, NTRK2, NTRK3, ROS1, or ALK gene fusion
  -  Unable to participate in an ongoing entrectinib (RXDX-101) clinical trial
  -  Willing and able to provide written, signed informed consent
  -  Medically suitable for treatment with entrectinib (RXDX-101)
  Exclusion Criteria:
  -  Currently enrolled in an ongoing clinical study with any other investigational agent

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry

Summary: This is a prospective German registry for patients with dyslipidemia with very high cardiovascular risk who principally meet the Gemeinsamer Bundesausschuss (G-BA) stipulations for Proprotein convertase subtilisin/kexin like type 9 inhibitor (PCSK9i) use, and are treated by office-based cardiologists or in lipid ambulances.

Detailed description: The study is purely observational, and will document data from the patient charts only. Treatment of patients will not be changed by this study, and all clinical decisions (including on frequency of visits) will be upon the discretion of the physician. No blood samples must be taken solely for the purpose of the study.
  The registry will include two types of centers: 1) office-based cardiologists and 2) specialized lipid ambulances (outpatient departments).
  Data on patient disease and treatment history will be collected a first documentation (retrospectively).
  The documentation time is 3 years per patient. After the baseline visit, patients are followed-up every 6 ± 2months (last visit at month 36). This interval is considered narrow enough not to miss important events (safety reporting, cardiovascular events, hospitalizations).
  Patients with stable (maintenance) lipid-lowering therapy (including those with existing PCSK9i therapy) or those with any therapy changes (including newly initiated PCSK9i treatment) will be documented in this study. Compared to the former group with stable drug treatment, the latter group will likely have major LDL-C changes during the first few weeks, which will be accounted for by (retrospective) monthly documentation in the first 3 months (data will be documented at the 6-month visit.
  The documentation periods will be substantially longer than in the controlled studies of the PCSK9i (endpoints were as early as 3 months), and thus will provide much-needed information about the long-term effects on LDL-C and other lipid parameters, safety, and drug retention rates. Longer follow-up periods would likely be compromised by high rates of (administrative) discontinuation rates.

Eligibility: Inclusion Criteria:
  -  • with familial, homozygous hypercholesterolemia, in whom pharmaceutical and diet options for lipid lowering have proved insufficient, or
  -  with confirmed familial, heterozygous hypercholesterolemia under consideration of the total familial risk, or
  -  with heterozygous familial or non‐ familial hypercholesterolemia or mixed dyslipidemia with
  -  therapy refractory course
  -  maximal dietary and pharmaceutical lipid lowering therapy - in any case documented over a 12-month period
  -  unsatisfactorily lowered LDL-C value (and thus with an indication for LDL apheresis)
  -  confirmed vascular disease
  -  other risk factors for cardiovascular events
  Exclusion Criteria:
  -  Concurrent participation of the patient in a clinical randomised study.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: HDL Acute Lipid Optimization in Homozygous Familial Hypercholesterolemia

Summary: Assess the effect on coronary atheroma of serial infusions of autologous selectively delipidated HDL/preβ enriched plasma following use of HDL Therapeutics PDS-2™ System

Detailed description: The PDS-2™ System is intended to reduce coronary atheroma in patients with Homozygous Familial Hypercholesterolemia (HoFH). Subjects will receive serial infusions of autologous selectively delipidated HDL/preβ enriched plasma following use of HDL Therapeutics' PDS-2 System.

Eligibility: Key Inclusion Criteria:
  -  Clinical diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) due to a defect in the LDL receptor, or the identification of a defect in apoB-100, or a gain of function of PCSK9, or a genetic defect resulting in the HoFH clinical phenotype
  -  No other condition that would preclude the subject from successfully completing the series of plasmapheresis visits in the investigator's opinion
  -  At least one (1) coronary artery study segment will be identified for each subject and all will remain constant throughout the study. The qualifying study segment(s) will have 20% to 40% stenosis.
  Key Exclusion Criteria:
  -  Planned change in current lipid lowering therapy
  -  Use of oral anticoagulants, unless the dose has been stable for 4 weeks
  -  LDL or plasma apheresis within 1 week prior to enrollment and through 8-week primary endpoint
  -  New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30%
  -  Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of enrollment

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: PRKAA2 Genetic Polymorphisms and Its Susceptibility to Chinese Type 2 Diabetes Mellitus and Diabetic Nephropathy

Summary: Metformin is a classical oral antidiabetic drug, often recommended to be the first-choice treatment of type 2 diabetes mellitus (T2DM). Based on the previous research on PRKAA2, STK11 and diabetes, this study aimed to investigate the distributive characteristic of PRKAA2 and STK11 polymorphisms and the potential influence of STK11polymorphisms on metformin efficacy among Chinese T2DM patients, discuss the association of PRKAA2 polymorphisms between T2DM patients and healthy subjects.


Eligibility: Inclusion Criteria:
  -  diagnosed with T2DM in keeping with the WHO criteria in 1999 [14], with fasting blood glucose (FBG) ≥ 7.0mmol ⁄ L and ⁄ or postprandial blood glucose (PBG) ≥ 11.1mmol ⁄ L; not using other antidiabetic drugs within the experimental period.
  Exclusion Criteria:
  -  other significant illness such as cancer, myocardial infarction, stroke, severe liver, and kidney disease

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Plasma Concentrations of Calcium, Phosphate, FGF23, Klotho, 25 (OH) D3 and 1,25 (OH) 2D3 From Patients Who Wants to Have Children

Summary: 1,25-dihydroxy-vitamin D3 (1,25 (OH) 2D3) or calcitriol regulates plasma calcium and phosphate concentrations in the blood by stimulating intestinal absorption and renal reabsorption of calcium and phosphate. 1.25 (OH) 2D3 is formed by the renal 1α25OH vitamin D-hydroxylase (Cyp27b1) and inactivated by the renal 25-hydroxy vitamin D-24-hydroxylase (Cyp24). Unpublished studies in mice revealed an inhibitory effect of 1.25 (OH) 2D3 on embryo implanation. An excess of 1.25 (OH) 2D3 could therefore lead to female infertility. The excess of 1.25 (OH) 2D3 could result from uncritical vitamin D intake with insufficient negative feedback by FGF23 / Klotho. The aim of the study is to identify patients with an excess of 1.25 (OH) 2D3.

Detailed description: The physiological institute of the University Tübinge has succeeded in preventing vascular calcification in Klotho-deficient mice by inhibiting osteogenic signal transduction. The animals reach an almost normal life span despite increased 1.25 (OH) 2D3, Ca2 + and phosphate plasma concentrations. The male animals are again fertilized, but not the female animals. However, if the plasma concentrations of 1.25 (OH) 2D3 are normalized by administration of a vitamin-poor diet, the female animals are fertilized within two weeks. Further investigations revealed an inhibitory effect of 1.25 (OH) 2D3 on the implantation of the embryo. In the meantime the 1,25 (OH) 2D3-dependent signal transduction could be revealed, which prevents the implantation of the embryo. The vitamin D receptor and the elements of signal transduction are also expressed in the human endometrium. It is therefore possible that increased 1.25 (OH) 2D3 plasma concentrations also prevent embryo implantation in humans.

Eligibility: Inclusion Criteria:
  -
  Exclusion Criteria:
  -  Known systemic diseases, e.g. Autoimmune disease, scleroderma, malignant disease

Relevance to patient case: not relevant