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

Clinical trial: The DEtermining Statin Intolerance FOr Rosuvastatin (DESIFOR) Trial

Summary: This study will enroll patients who previously were not able to tolerate being on a statin medication due to muscle-related side effects. Research has shown that many people who have muscle symptoms on statin therapy do not experience the same side effects if they try it again later. This study is part of a larger effort to:
  -  See how common it is for patients to still be intolerant of statin medication after trying it a second time; and
  -  For those patients who do tolerate being on a statin after trying it a second time, see how common it is for them to still be taking the statin 3 months after completing the main part of the study.
  Patients who agree to participate will be given a 5 month randomly allocated supply of statin and placebo and track their symptoms weekly.

Detailed description: This study is a single center, double-blinded randomized controlled trial for patients eligible for statin therapy by current guidelines, but not on statin therapy due to a history of statin intolerance. Patients will be provided a "DESIFOR" kit which includes 5 randomly allocated 4-week blister packs of capsules containing either 20mg of rosuvastatin or placebo. While blinded to treatment, patients will document the severity of musculoskeletal symptoms every week using a numerical scale. The primary endpoint will be the difference between the mean musculoskeletal symptom score while randomized to statin therapy compared to the mean score while on placebo. After completion of the study, the results will be unblinded and reviewed at a 6 month follow-up visit with the patient and, for patients with symptoms found to not correlate with statin therapy, a trial of non-blinded statin therapy over the next 3 months will be recommended. This study will serve as a pilot study to determine the feasibility and potential benefits of a larger multicenter trial with similar aims.

Eligibility: Inclusion Criteria:
  -  Adults age 21-75 years old
  -  Statin eligible according to the 2013 ACC/AHA cholesterol guidelines, including individuals with:
  -  Known ASCVD
  -  Diabetes
  -  LDL-C > 190mg/dl
  -  10-year ASCVD risk >7.5%
  -  Statin intolerant
  -  Defined by discontinuation of at least 2 separate statins due to potential musculoskeletal side effects
  Exclusion Criteria:
  -  Women who are pregnant, nursing or attempting to become pregnant.
  -  Individuals deemed to be at very high CVD risk and therefore appropriate for a PCSK9 inhibitor including:
  -  Individuals with familial hypercholesterolemia with markedly elevated LDL-C levels
  -  Individuals with known ASCVD and recurrent events
  -  Individuals who are not otherwise clinically indicated to take 20mg rosuvastatin
  -  Individuals who experienced severe reactions in the past, including:
  -  Rhabdomyolysis
  -  Severe myositis
  -  Anaphylaxis

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

Clinical trial: Impact of B. Bifidum 900791 Intake on Breast Milk Characteristics of Obese Mothers

Summary: Human breast milk harbours a specific microbiota including bacteria from the Lactobacillus and Bifidobacterium genera, that contribute to the bacterial colonization of the infant gut in the post-natal period. An entero-mammary pathway has been suggested by which selected bacteria from the maternal gut would be transmitted to the mammary gland through dendritic cell trafficking by the lymphatic pathway. Accordingly, some studies have detected the presence of probiotic strains in breast milk from mothers who were consuming them. The administration of probiotic supplements to lactating mothers has also been shown to modulate milk concentrations of inflammatory markers and metabolic hormones, impacting positively the infant health. Noteworthily, many of these inflammatory and hormonal biomarkers are altered in the breastmilk from pre-pregnancy obese mothers, compared with these who were normal-weight, possibly affecting the infant health. It is unclear whether the breast milk microbiota of obese mothers is altered and the impact of probiotic administration on the breastmilk microbiota and on the normalization of breastmilk alterations in obese mothers is unknown.
  Based on these antecedents, the aim of this study is to determine if the administration of a B. bifidum 900791-containing foodstuff to mothers during the perinatal period normalizes the breast milk concentrations of interleukin (IL)-6, C-Reactive Protein (CRP), insulin, adiponectin and resistin, and the microbiota of obese mothers, compared with normal-weight mothers.


Eligibility: Inclusion Criteria:
  -  Women in their last month of pregnancy, who were normal-weight (18.5<BMI<25kg/m2) or who were obese (BMI>30kg/m2) before pregnancy, and their children
  Women recruited should have expressed their wish to have their child through normal delivery, and to breastfeed at least during the first month post-partum.
  Exclusion Criteria:
  -  Women with chronic diseases (type 2 diabetes, renal diseases, autoimmune diseases, tumor, chronic inflammatory diseases, etc.).
  -  Women with a history of digestive surgery.
  -  Women whose children are hospitalized more than 24hours in the neonatal unit
  -  Women who require antibiotic treatment during the perinatal period.

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

Clinical trial: A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH

Summary: AK102 is being developed for the treatment of HoFH. The study will be conducted in 2 parts, part 1 is open label, single arm study to evaluate the safety, tolerability and efficacy of PCSK9 inhibitor AK102, and part 2 is double blind, randomized, placebo controlled study to evaluate the efficacy and safety of PCSK9 inhibitor AK102. The treatment period will last 12 week.


Eligibility: Inclusion Criteria:
  -  Males and females, ≥18 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 pre-existing, lipid-lowering therapies (statins in combination with ezetimibe) 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:
  -  Received LDL plasma replacement therapy within 8 weeks before Investigational product administration
  -  Received Lomitapide or Mipomersen within 5 months before Investigational product administration
  -  Received prior treatment with PCSK9 inhibitors or AK102.
  -  Unexplained creatine kinase (CK) ≥ 5 times the upper limit of normal (ULN)
  -  Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 500 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.
  -  Known allergic reactions to any ingredients of AK102
  -  Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study as judged by the Investigator and/or Medical Monitor.

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

Clinical trial: Impact of Evolocumab in Cardiac Transplant Patients With CAV

Summary: Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (repatha) is an FDA-approved drug for lowering LDL in patients who have not received a heart transplant. This drug works as a PCSK9-inhibitor. The primary objective of this study is to measure the impact of PCSK9-inhibitors on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline.

Detailed description: Heart transplant remains the treatment of choice for patients with advanced heart failure. Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of the donor heart, and limits long term survival after transplant. The pathophysiology of CAV is complex and involves smooth muscle proliferation, inflammatory infiltrates, and lipid deposition. To date, only statin therapy has reduced CAV-related mortality. PCSK9 inhibitors are a new lipid lowering therapy shown to reduce cardiovascular clinical events in patients with coronary artery disease. We hypothesize that PCSK9 inhibition via evolocumab will significantly lower LDL and be well-tolerated in transplant patients with CAV. This phase II, open label, single center trial with enroll up to 40 heart transplant patients with CAV for treatment with evolocumab for one year. The primary outcome will be percent change in LDL at 12 weeks. Secondary outcomes will include change in CAV progression, impact of evolocumab on immunosuppression regimens and transplant rejection, and change in serum lipids after 52 weeks. Results of this study are intended to provide safety data in heart transplant patients with CAV and assess secondary outcomes including CAV progression and impact on immunosuppression and transplant rejection.

Eligibility: Inclusion Criteria:
  -  Heart transplant patients 19-80 years of age
  -  Coronary allograft vasculopathy grade 1 or 2 documented by left heart cardiac catheterization
  -  Able to provide signed informed consent
  Exclusion Criteria:
  -  CAV grade 3
  -  Rejection requiring IV therapy in the prior 3 months
  -  Infection requiring IV therapy in the prior 3 months
  -  Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal
  -  Current or recent use of a PCSK9 inhibitor within the past 12 weeks
  -  Organ transplant recipient other than heart
  -  Renal dysfunction defined as GFR < 20 ml/min
  -  Known allergy to evolocumab or its components

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Abnormalities of the Eye's Anterior Chamber, Iris, Cornea and Lens

Summary: This study will investigate congenital or developmental eye abnormalities that affect the iris, cornea and lens, and are usually accompanied by elevated pressure within the eye. These disorders can cause vision loss, and the increased eye pressure can lead to glaucoma, a condition that may also cause loss of eyesight.
  Patients with eye anterior chamber eye disease, such as Axenfeld's syndrome, Rieger's anomaly, Peter's anomaly, iridocorneal endothelial syndrome, megalocornea, ocular hypertension, and others, are eligible for this study. Participants will have a medical examination, family history, and comprehensive eye examination. Tests and procedures may include photographs of the cornea, iris, and the structure through which fluid that normally circulates behind the cornea drains out of the eye. Some patients may undergo indentation tonography to measure how easily this fluid drains. In this procedure, the patient lies on an examination table and both eyes are numbed with eye drops. A small instrument (tonometer) is placed on the surface of one eye, and with the other eye, the patient looks at an overhead light. Other tests may include photographs of the back of the eye and ultrasound imaging of the structures of the eye. A blood sample may be drawn to study the genetic disorder responsible for the disease. Patients will have follow-up examinations every 6 months for the duration of the study.
  Medical or surgical therapy will be recommended, as appropriate, for patients who develop elevated eye pressure or vision loss.

Detailed description: This study will concentrate on abnormalities of the anterior chamber with or without elevated intraocular pressure. The purpose of the study will be to determine if there is a common pathogenesis shared by these conditions. A natural history study of 40 individuals with these diseases will utilize clinical measurements and photographs for documentation of this hypothesis. In addition, surgical specimens, when available, will be studied.

Eligibility: The eye conditions to be studied include Axenfeld's syndrome, Rieger's anomaly, Peter's anomaly, (all with or without glaucoma), Iridocorneal Endothelial syndrome, Aniridia, Pigment Dispersion syndrome, Megalocornea and other conditions with clinical abnormalities of the anterior chamber.
  Patients will not be included in the study if they do not fit the morphologic characteristics of the disease in question or if the patient's general medical condition or other related factors make it impossible for him or her to continue participation in the study.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Cardiovascular Evaluation of Patients With High Cholesterol and Normal Volunteers

Summary: Homozygous familial hypercholesterolemia is a rare inherited disease of metabolism. It occurs in less than 1 in 1 million people within the United States. Patients with the disease are typically children and young adults who develop heart disease early in life. Children less than age 5 years with this disease have suffered heart attacks and death.
  The normal process that removes cholesterol particles from the blood stream does not work in patients with this disease. It causes cholesterol to build-up in the arteries and leads to hardening of the arteries (atherosclerosis).
  The goal of this study is to detect and measure atherosclerosis in these patients before it becomes permanent and potentially life threatening. Patients with this disease can participate in this study. Researchers plan to evaluate patients with homozygous familial hypercholesterolemia using new and standard methods for detecting atherosclerosis.
  Researchers plan to use information gathered during this study to develop new, promising treatments such as liver transplantation and gene therapy.

Detailed description: Familial hypercholesterolemia is an autosomal co-dominant disorder resulting in abnormal LDL receptor function, profoundly elevated concentrations of low density lipoproteins, accelerated atherosclerosis and death by early adulthood. This disease is heterogeneous in both the degree of LDL receptor dysfunction as well as the age of death. Liver transplantation has been demonstrated to virtually normalize plasma lipoprotein concentrations in homozygous FH and the recent cloning of a functional LDL receptor gene holds promise in the definitive treatment of this condition. We propose performing longitudinal sequential cardiologic studies utilizing noninvasive techniques in homozygous patients with well-characterized LDL receptor defects. Sequential cardiovascular study of these patients will not only characterize the progression of atherosclerosis heart disease in this disease, it may also permit the identification of individuals with would be likely to benefit from liver transplantation and/or genetic engineering.

Eligibility: -  INCLUSION CRITERIA:
  Fasting cholesterol greater than 500 mg/dl, low density lipoprotein cholesterol greater than 400 mg/dl, and triglycerides less than mg/dl.
  Family history of hypercholesterolemia and/or cardiovascular disease before the age of 60 years.
  Tendinous and tuberous xanthomas.
  Arcus corneae before the age of 30.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Study of Brain Blood Flow During Induced Hypercapnia (Excess Blood Carbon Dioxide)

Summary: This study will evaluate magnetic resonance imaging (MRI ) methods for measuring changes in the brain's blood flow during hypercapnia (a condition of excess carbon dioxide in the blood). MRI is a diagnostic tool that uses a large magnet and radio waves to produce images of the body without X-rays.
  Healthy normal volunteers in this study may have as many as six MRI scans over a 2-year period. For this procedure, the person lies on a stretcher placed in a strong magnetic field produced by the MRI machine. During the scan, the person's blood carbon dioxide (CO2 ) levels will be increased either by: 1) breathing air mixtures containing up to 5% CO2; or 2) receiving an intravenous (I.V.) injection of a drug called acetazolamide.
  Persons who breathe CO2 will have their heart rate, blood pressure and oxygen levels monitored throughout the procedure. Those receiving acetazolamide will have the drug injected intravenously (I.V.) into an arm vein. If the volunteer experiences any unpleasant side effects from the CO2 or acetazolamide, the study will be stopped.
  The information gained from this study will be used to develop better ways to study brain function, possibly leading to better diagnostic and treatment methods.

Detailed description: Advances in MR perfusion imaging have provided clinical researchers with the opportunity to quantitate regional increases in cerebral blood flow. The purpose of this study is to acquire the technical experience required to perform MR perfusion imaging studies of the hypercapnic cerebral blood flow response. Cerebral blood flow will be increased by inhalation of carbogen (an air mixture containing 5% CO2) or IV injection of the carbonic anhydrase inhibitor acetazolamide. The technical experience obtained in this study will be used to design a study of the pharmacological and physiological mechanisms underlying cerebral blood flow increases during hypercapnia.

Eligibility: INCLUSION CRITERIA:
  Any normal volunteer above the age of 18 years old who is capable of giving informed consent.
  EXCLUSION CRITERIA:
  Subjects will be excluded if they have contraindications to MR scanning, such as the following: aneurism clip, implanted neural stimulator, implanted cardiac pacemaker or autodefibrillator, chochlear implant, ocular foreign body (e.g., metal shavings), or insulin pump. Also, subjects will be excluded if they have panic disorder or migrane (because of possible complications with CO2 inhilation), or if they have cirrhosis, are on high dose aspirin therapy, or have an allergy to acetazolamide injection). Subjects will be excluded if they have allergies to sulfonamide drugs or if they have a chronic respiratory illness.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Gene Therapy in Treating Patients With Cancer of The Liver

Summary: Phase I trial to study the effectiveness of gene therapy with the p53 gene in treating patients who have cancer of the liver that cannot be surgically removed. Inserting the p53 gene into a person's tumor may improve the body's ability to fight liver cancer.

Detailed description: OBJECTIVES:
  I. Determine the safety of adenovirus p53 construct (adeno-p53) in patients with hepatocellular carcinoma.
  II. Investigate the potential effects of intralesional adeno-p53 given by monthly percutaneous injections in these patients.
  OUTLINE: This is a dose escalation, multicenter study.
  Patients receive adenovirus p53 construct by percutaneous injection to a maximum of two lesions on day 1. Treatment is repeated every 28 days for up to 6 courses. In the absence of dose-limiting toxicity (DLT) in the first cohort of 6 patients treated, subsequent cohorts of 6 patients each receive escalating doses of the drug on the same schedule. If DLT occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and that dose is declared the maximum tolerated dose. Study treatment may continue in the absence of disease progression and unacceptable adverse events.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed unresectable hepatocellular carcinoma (HCC) or highly suspicious for HCC based on CT scan and elevated alfafetoprotein
  -  Measurable disease by abdominal CT scan Accessible (peripheral) lesions
  -  No metastatic disease
  PATIENT CHARACTERISTICS:
  -  Age: Over 18
  -  Performance status: ECOG 0-2
  -  Life expectancy: At least 12 weeks
  -  Platelet count at least 60,000/mm3
  -  Absolute neutrophil count greater than 1,500/mm3
  -  Prothrombin time of no greater than 16 seconds after administration of fresh frozen plasma
  -  Bilirubin no greater than 3.0 mg/dL
  -  Creatinine less than 1.5 mg/dL
  -  Child's class A or B cirrhosis eligible
  -  No uncontrolled infection Not pregnant or breast feeding
  -  No unstable or severe intercurrent medical condition
  PRIOR CONCURRENT THERAPY:
  -  At least 4 weeks since prior chemotherapy
  -  At least 4 weeks since prior radiation therapy
  -  No prior hepatic transplantation
  -  No more than 1 prior systemic regimen for hepatocellular carcinoma allowed
  -  No concurrent therapy with other investigational agents
  -  No prior gene therapy
  -  No prior intralesional therapy

Relevance to patient case: not relevant