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

Clinical trial: A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy in Japanese Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-050)

Summary: This study will evaluate the effects of anacetrapib (MK-0859) on low-density lipoprotein-cholesterol (LDL-C) when compared to placebo in Japanese participants with heterozygous familial hypercholesterolemia when added to an existing statin lipid-modifying therapy.


Eligibility: Inclusion Criteria:
  -  If female, cannot be of reproductive potential
  -  Diagnosed with heterozygous familial hypercholesterolemia
  -  Have been treated with an appropriate and
  stable dose of statin± other lipid-lowering medication(s) for at least 6 weeks
  Exclusion Criteria:
  -  Previously participated in a study with a cholesteryl ester transfer protein (CETP) inhibitor
  -  Homozygous familial hypercholesterolemia
  -  Severe chronic heart failure
  -  Uncontrolled cardiac arrhythmias, myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery by-pass graft (CABG), unstable angina, or stroke within 3 months

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

Clinical trial: Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study

Summary: Ezetimibe has been shown to inhibit cholesterol absorption and several lines of evidence from in vitro systems and animal models suggest that this effect is associated with an increase in low-density lipoprotein (LDL) receptor expression in the small intestine. The impact of a treatment with ezetimibe on intestinal gene expression and protein mass levels of LDL receptor and other key genes involved in intestinal cholesterol homeostasis will be examined in dyslipidemic men with insulin-resistance. In the present study, gene expression studies and protein mass levels will be assessed on duodenal biopsies by real-time polymerase chain reaction (rt-PCR) and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. The primary objective of this proposal is to examine the effects of ezetimibe on intestinal gene expression (rt-PCR) and protein mass levels (LC-MS/MS) of LDL receptor in dyslipidemic men with insulin-resistance. The secondary objective is to examine the impact of ezetimibe treatment on intestinal gene expression and protein mass levels of sterol regulatory element-binding protein (SREBP)-2, Niemann-Pick C1-Like1 (NPC1L1), ATP binding cassette gene (ABCG)-5/8, proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase.
  Primary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of LDL receptor in dyslipidemic men with insulin-resistance.
  Secondary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase in dyslipidemic men with insulin-resistance.


Eligibility: Inclusion Criteria:
  -  Men aged between 18-60 years
  -  Waist circumference > 102 cm
  -  HDL-cholesterol < 1.1 mmol/L
  -  Triglycerides > 1.7 mmol/L
  -  Fasting blood glucose > 6.1 mmol/L
  -  Normal blood pressure (<130/85)
  Exclusion Criteria:
  -  Women
  -  Men < 18 or > 60 years
  -  Smokers (> 1 cigarette/day)
  -  Body weight variation > 10% during the last 6 months prior to the study baseline
  -  Subjects with a previous history of cardiovascular disease
  -  Subjects with type 2 diabetes
  -  Subjects with a monogenic dyslipidemia
  -  Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa
  -  Subjects with endocrine or gastrointestinal disorders
  -  History of alcohol or drug abuse within the past 2 years
  -  Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.

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

Clinical trial: Gene Analysis and Treatment Optimization in Chinese Homozygous Familial Hypercholesterolemia

Summary: Identify new or novel genes which may impact on cholesterol level, and establish the relationship between those gene mutations with atherosclerosis, as well as responses to lipid-lowering drugs.

Detailed description: To better understand the genetics basis for LDL-C elevation and develop an optimized lipid-lowering strategy, we propose to do the following studies:
  1. To establish a China HoFH registry, and collect DNA and blood samples from all available family members of each proband (pedigrees);
  2. To detect gene mutations known to cause FH and identify family suitable for future whole genome sequencing aimed to identify novel genes controlling cholesterol levels.
  3.To establish the relationship between types of gene mutations and lipid and atherosclerosis profile, as well as responses to lipid-lowering agents.

Eligibility: Inclusion criteria:
  Patients of any age and sex who meet clinical or genetic criteria for hoFH as follows:
  -  Cutaneous xanthomata before the age of ten years
  -  LDLC > 13 mmol/L before treatment or > 7.76 mmol/L despite treatment
  -  Phenotypic features in keeping with HeFH in both parents
  Exclusion criteria:
  Inability of patient, or, if less than 18, a parent, to sign informed consent.

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

Clinical trial: Effect of Alirocumab on Lipid Metabolism in Adults With Elevated LDL-Cholesterol

Summary: Primary Objective:
  To assess the effects of subcutaneous (SC) doses of alirocumab on the elimination (measured by Fractional Clearance Rate (FCR)) of apolipoprotein B (apoB) in low density lipoprotein (LDL) in adults with mildly elevated LDL-cholesterol (LDL-C).
  Secondary Objectives:
  To assess the effects of SC doses of alirocumab on:
  -  Various parameters of the metabolism and turnover in plasma of different lipoproteins
  -  Plasma lipids concentration: total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, low density lipoprotein cholesterol (LDL-C), apoB, lipoprotein(a) (Lp(a))
  -  Lipoprotein particle size profile
  -  PCSK9 (free and total) concentrations in serum To assess safety and tolerability of alirocumab. To assess emergence of anti-alirocumab antibodies. To document serum alirocumab concentrations.

Detailed description: Total duration of the study per subject is 26 weeks, including a screening period of ≤ 4 weeks, placebo treatment period of 4 weeks, alirocumab treatment period of 10 weeks, and a follow up period of 8 weeks.

Eligibility: Inclusion criteria:
  Generally healthy; LDL-C level in serum or plasma ≥ 100 mg/dL and < 190 mg/dL at Screening.
  Exclusion criteria:
  -  LDL-C ≥ 160 mg/dL at Screening if more than 2 major Coronary Heart Disease risk factors, as defined in National Cholesterol Education Program guidelines.
  -  Receiving treatment of any kind for hyperlipidemia within 6 weeks of enrollment.
  The above information is not intended to contain all considerations relevant to a patient'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: A 52 Week Study To Assess The Use Of Bococizumab (PF-04950615; RN316) In Subjects With Heterozygous Familial Hypercholesterolemia

Summary: This is a multicenter, randomized study in subjects with heterozygous familial hypercholesterolemia receiving highly effective statins to assess the safety, efficacy and tolerability of Bococizumab (PF-04950615; RN316) to lower LDL-C.


Eligibility: Inclusion Criteria:
  -  Treated with a statin.
  -  Fasting LDL-C > 70 mg/dL and triglyceride <=400 mg/dL.
  -  High or very high risk of incurring a cardiovascular event.
  -  Heterozygous familial hypercholesterolemia.
  Exclusion Criteria:
  -  Pregnant or breastfeeding females.
  -  Cardiovascular or cerebrovascular event of procedures during the past 30 days.
  -  Congestive heart failure NYHA class IV.
  -  Poorly controlled hypertension.

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

Clinical trial: The Evaluation of Bococizumab (PF-04950615;RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects

Summary: This study evaluates the PCSK9 inhibitor, Bococizumab (PF-04950615;RN316), compared to placebo, in reducing the occurrence of major cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and unstable angina requiring urgent revascularization, in high risk subjects who are receiving background lipid lowering therapy and have cholesterol laboratory values of LDL-C >/= 70 mg/dL (1.8 mmol/L) or non-HDL-C >/= 100 mg /dL (2.6 mmol/L).

Detailed description: The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents. These indicated that bococizumab was not likely to provide value to patients, physicians, or shareholders. The decision was not based on a recommendation by the independent Data Monitoring Committee to stop the program.

Eligibility: Inclusion Criteria:
  -  Must be on background lipid lowering treatment.
  -  Must be at high risk of a CV event.
  -  Must have an LDL C >/=70 mg/dL (1.8 mmol/L) or non-HDL-C >/= 100 mg/dL (2.6 mmol/L).
  Exclusion Criteria:
  -  Planned coronary (PCI or CABG) or other arterial revascularization.
  -  New York Heart Association Class IV congestive heart failure or left ventricular ejection fraction < 25% by cardiac imaging.
  -  Chronic renal insufficiency with creatinine clearance of <30 ml/min/1.73m^2 by MDRD formula or with end state renal disease on dialysis.
  -  History of hemorrhagic stroke.
  -  Prior exposure to bococizumab or other investigational PCSK9 inhibitor.

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

Clinical trial: The Evaluation of Bococizumab (PF-04950615; RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects

Summary: This study evaluates the PCSK9 inhibitor, Bococizumab (PF-04950615;RN316), compared to placebo, in reducing the occurrrence of major cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and unstable angina requiring urgent revascularization in high risk subjects who are receiving background lipid lowering therapy and have cholesterol laboratory values of LDL-C >/= 100 mg/dL (2.6 mmol/L) or non-HDL-C >/=130 mg/dL (3.4 mmol/L).

Detailed description: The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents. These indicated that bococizumab was not likely to provide value to patients, physicians, or shareholders. The decision was not based on a recommendation by the independent Data Monitoring Committee to stop the program.

Eligibility: Inclusion Criteria:
  -  Must be on background lipid lowering treatment.
  -  Must be at high risk of a CV event.
  -  Must have an LDL C >/=100 mg/dL (2.6 mmol/L) OR non HDL C >/=130 mg/dL (3.4 mmol/L).
  Exclusion Criteria:
  -  Planned coronary (PCI or CABG) or other arterial revascularization.
  -  New York Heart Association Class IV congestive heart failure or left ventricular ejection fraction < 25% by cardiac imaging.
  -  Chronic renal insufficiency with creatinine clearance of <30 ml/min/1.73m^2 by MDRD formula or with end state renal disease on dialysis.
  -  History of hemorrhagic stroke.
  -  Prior exposure to bococizumab or other investigational PCSK9 inhibitor.

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

Clinical trial: French Digestive Polyposis Cohorte Family Adenomatous Polyposis With APC and MYH Gene Mutations , Cowden's Disease With PTEN Gene Mutation, Peutz Jeghers Disease With STK 11 Gene Mutation ,juvénil Polyposis With SMAD 4 Gene Mutation , Serrated and Hyperplastic Polyposis

Summary: French cohorte about polyposis digestive diseases

Detailed description: Family Adenomatous Polyposis APC and MYH Genes Peutz Jeghers Disease Cowden Disease Festooned polyposis Juvenile polyposis Hyperplastic polyposis

Eligibility: Inclusion Criteria:
  -  APC Gene mutation
  -  MYH Homozygote mutation
  -  COWDEN Disease with PTEN gene mutation
  -  Peutz Jeghers Disease with STK 11 gene mutation
  -  Juvenile polyposis with SMAD 4 gene mutation
  Exclusion Criteria:
  -  heterozygote MYH Gene Mutation

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

Clinical trial: Carfilzomib for the Prevention of Graft Versus Host Disease

Summary: The aim of this study is to evaluate the safety and efficacy of Carfilzumib, which is a novel biological agent used in the treatment of multiple myeloma in preventing graft-versus-host disease, after stem cells transplantation from unrelated donors.


Eligibility: Inclusion Criteria:
  1. Patients with MDS/AML
  2. 18 years or older and willing and able to comply with the protocol requirements.
  3. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
  4. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
  5. Patients conditioned with reduced intensity or reduced toxicity conditioning i.e. Fludarabine combine with Treosulfan or 2-4 days of I.V Busulfan.
  6. Patients must sign written informed consent.
  7. Adequate birth control in fertile patients.
  Exclusion Criteria:
  1. Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
  2. Patients with respiratory failure (DLCO < 30%).
  3. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
  4. Patients with > grade II liver renal toxicity.
  5. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
  6. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
  7. Creatinine > 2.0 mg/dl
  8. ECOG-Performance status > 2
  9. Uncontrolled infection
  10. Pregnancy or lactation
  11. CNS disease involvement
  12. Pleural effusion or ascites > 1 liter.

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

Clinical trial: A Phase I Study in Healthy Volunteers to Assess the Effect of Cytochrome3A4 (CYP3A4) Inhibitors (Diltiazem and Itraconazole) on the Pharmacokinetics (PK) of AZD3293 and the Effects of AZD3293 on the Pharmacokinetics of Midazolam, a Cytochrome 3A4 and Cytochrome 3A5 (CYP3A4/CYP3A5) Substrate

Summary: This study is a single-center, open-label, 3-group, fixed-sequence drug-drug interaction study to assess the effect of coadministration of multiple-dose itraconazole or diltiazem on the single-dose PK of AZD3293 and the effects of coadministration of single- and multiple-dose AZD3293 on the single-dose PK of midazolam. The study will also evaluate the safety and tolerability of single and multiple oral doses of AZD3293, alone and in combination with itraconazole, diltiazem, and midazolam in healthy young subjects.AZD3293 is being developed for the treatment of Alzheimer's disease


Eligibility: Inclusion Criteria:
  -  Provision of signed, written, and dated informed consent prior to any study-specific procedures Male and nonfertile female healthy subjects, aged 18 to 55 years at the time of consent
  -  Body weight ≥50 to ≤100 kg and body mass index (BMI) ≥19 to ≤30 kg/m2
  -  Clinically normal findings on physical examination in relation to age, as judged by the Investigator
  -  Male healthy subjects must be willing to use barrier contraception, ie, condoms, even if their partners are post-menopausal, surgically sterile, or using accepted contraceptive methods, from the first day of dosing until 3 months after the last dose of investigational product (IP)
  Exclusion Criteria:
  -  Participation in any prior study of AZD3293
  -  History of any clinically significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results, or may limit the subject's ability to participate in the study
  -  History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
  -  History of previous or ongoing psychiatric disease/condition including psychosis, affective disorder, anxiety disorder, borderline state and personality disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV), as assessed by the Mini-International Neuropsychiatric Interview (MINI)

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

Clinical trial: French Observatory of Familial Hypercholesterolemia in Cardiology

Summary: The Family Hypercholesterolemia remains poorly diagnosed disease with an outlet sometimes suboptimal care. However, the Family Hypercholesterolemia exposes patients concerned at increased cardiovascular risk.
  The frequency of familial hypercholesterolemia in cardiologic is little studied and remains unknown, and there is little data on the profile of patients, diagnostic methods and management.
  Main objectives:
  -  Establish a monitoring patients with hypercholesterolemia Family cardiology in France
  -  Characterize the Family hypercholesterolemia in cardiology, including assessing the frequency of the most severe forms, which are at higher cardiovascular risk.


Eligibility: Inclusion Criteria:
  -  coronary patients
  -  who agreed to participate
  -  high LDL-c levels: * LDL-c> = 1.9g / l without lipid lowering treatment according to the diagnostic score of Family Hypercholesterolemia these coronary patients with LDL> 1.9g / l may possibly or probably be achieved Hypercholesterolemia Family.
  or
  * LDL-c> = 1.6g / l in lipid-lowering treatment, the reduction of LDL-c average expected under standard lipid-lowering therapy (statin alone) being 30-40% of these patients had therefore pretreatment levels greater than 2 g / l or greater than 2.5 g / l and may possibly or probably be achieved Family Hypercholesterolemia after the diagnostic score.
  Exclusion Criteria:
  -  Expressed refusal to participate in the observatory
  -  Age ≤ 18

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

Clinical trial: Identification of CETP as a Marker of Atherosclerosis

Summary: The reverse cholesterol transport (RCT) pathway, which involves the centripetal movement of free cholesterol from peripheral tissues, including the vessel wall, to the liver represent the primary mechanism by which HDL protects against atherosclerosis and by which it may induce plaque regression. Recent data reveal that the capacity of HDL to efflux cholesterol from macrophages, a metric of HDL function reflecting the initial step of the RCT, is clinically relevant, displaying a strong inverse association with both carotid intima-media thickness and the severity of angiographic CAD; such observations were independent of HDL-C levels.
  In human, the Cholesteryl Ester Transfer Protein (CETP), represents a key protein of the RCT pathway and mediates redistribution of neutral lipids between lipoproteins, has been identified as a potential therapeutic target against atherosclerosis. It is known that CETP activity correlates with HDL-C levels and represents a key modulator of the ability of whole plasma to mediate free cholesterol efflux from human macrophages.
  Recent studies showed that 23% of endogenous plasma CETP activity variability is explained by plasma LDL-C (12.0%), HDL-C (6.4%) and TG (4.4%) whereas sex and BMI accounted together for only 0.7% of its variability. Scoring patients for cardiovascular risk on the basis of their plasma lipid levels (TC, TG, LDL-C and HDL-C), revealed that patients with high cardiovascular risk (score ≥3) displayed a mean endogenous plasma CETP activity above 34%. Therefore plasma CETP activity represents a potent indicator of cardiovascular risk in patients with metabolic disorders since it integrates major independent risk factors.
  The objective of this study is to decipher the relationship between CETP, HDL efflux capacity and the development of atherosclerosis in humans in order to identify CETP as a potent biomarker of atherosclerosis distribution.


Eligibility: Inclusion Criteria:
  -  Signed informed consent prior to initiation of the study
  -  Men and women aged 18 or more years
  -  Patients displaying at least one abnormal plasma lipid parameter and/or receiving a lipid-lowering therapy unchanged for at least 3 months.
  Exclusion Criteria:
  -  Current significant renal disease, including: nephrotic syndrome; chronic renal failure and/or serum creatinine >1.7 x upper limit of the reference range (ULRR)
  -  Uncontrolled hypothyroidism defined as TSH >2 x ULRR
  -  Active hepatobiliary disease, including chronic hepatitis B or hepatitis C infection (confirmed by serology); or an aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.0 x ULRR
  -  Any prior history of malignancy or current cancer
  -  Current chronic or acute inflammatory syndrome defined as CRP>10 mg/l

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

Clinical trial: The Mechanism of TCF7L2 and SLC30A8 on Antipsychotic-induced Metabolic Syndrome

Summary: Almost all of antipsychotics can induce metabolic syndrome,Genetic factors play a key role in the development of metabolic syndrome,TCF7L2 and SLC30A8 are strongestly correlated with metabolic syndrome.Moreover,Antipsychotics have an effect on the expression of TCF7L2 and SLC30A8 genes.It indicates the variations of TCF7L2 and SLC30A8 play an important part in the development of antipsychotics-induced metabolic syndrome.

Detailed description: -  In this study, we will determine the effect of olanzapine on the expression of TCF7L2 and SLC30A8.
  -  The relationship of the polymorphism of TCF7L2 and SLC30A8 with antipsychotic-induced metabolic syndrome in schizophrenia patients.

Eligibility: Inclusion Criteria:
  -  Clinical diagnosis of first episode schizophrenia
  -  Must be able to swallow tablets
  -  Take only one antipsychotics
  Exclusion Criteria:
  -  liver or renal or cardiovascular diseases
  -  pregnant or lactating women
  -  drug and alcohol dependence

Relevance to patient case: not relevant