Active clinical trials for "Genetic Predisposition to Disease"

The study aims to comprehensively introduce Long-read Genome sequencing (LR-GS) based genetic testing into clinical routine. In order to demonstrate the superiority of untargeted LR-GS over Short-read Genome sequencing (SR-GS) to establish firm genetic diagnoses, the investigators will rely on a multi-center "Translate Nationale Aktionsbündnis für Menschen mit Seltenen Erkrankungen" (Translate National Action Alliance for People with Rare Diseases Germany, TNAMSE) cohort of unsolved patients with neurological, neurodevelopmental, and imprinting disorders that is expectedly enriched for complex genomic variation. Within the framework of genomDE, the investigators will then implement, for the first time, LR-GS in the diagnostic work-up of a prospective cohort of patients with a broad range of clinical indications including rare diseases and cancer predisposition.

Covid-19 outbreak has caused death of millions of people because of not only the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself but also infection dependent complications. Abnormalities in thrombotic events leads to some of these complications which eventually result in emboli. The endothelial damage caused by the virus interacting with ACE2 on the host cells leads to the activation of coagulation cascade. Accumulation of byproducts of the cascade might have some roles in embolism inducing risk of organ damage, other life-threatening problems, and even death. To enlighten the factors triggering embolism, the investigators have focused on genetic changes such as polymorphisms and mutations in certain genes in DNA samples coming from intensive care unit (ICU) patients.

AF is the most common sustained arrhythmia in adults and its prevalence increases with advancing age. In this study, we aim to determine whether the published genome-wide polygenic scores for atrial fibrillation (GPSAF) can facilitate AF screening by accurately discriminating between patients with low and high risk for AF. All included patients are participating in the MHI biobank, an ongoing funded institutional DNA bank and clinical registry approved by the research ethics board where included patients consent for future genetic research. The study will compare AF detection rate using a 3 months near continuous monitoring in individuals with a high GPSAF with matched individuals from the bottom GPSAF.

Quantitative faecal immunochemical testing (qFIT) is used to test for blood within faeces that cannot always be visible. The presence of blood in the stool has been shown to be a finding where there may be a problem within the large bowel. The test is able to give a numeric value to the blood in the stool and based on this result, further investigations can be planned, or if normal reassurance given. The test is not perfect and minor bowel problems such as haemorrhoids (piles) can give a raised result. However, we have also seen raised results in people who when investigated have a completely normal large bowel. A small degree of 'physiological' non-visible bleeding is likely a normal part of life and for the majority this does not lead to a raised qFIT result. It may be the case in people who have a raised qFIT but then go on to have a completely normal colonoscopy (telescope investigation of the large bowel) that there is a genetic predisposition that increases the amount of normal 'physiological blood' that they produce. This leads to the test being falsely positive and the person undergoing an unnecessary investigation. This study aims to use saliva to test for known genetic markers that effect blood clotting and can increase how much someone bleeds. By comparing the occurrence of these genetic markers in people with a raised qFIT and normal colonoscopy to those with a normal qFIT and normal colonoscopy, we can test this theory. Should this be the case it will help explain why the test can be raised in normal large bowel and could lead to different levels of positivity being used for different people.

Smoking is the leading cause of avoidable death in the world. Smoking is associated with the development of cardiovascular and respiratory diseases, as well as being considered a leading cause of cancer death. Data show that smokers have increased cardiovascular risk in relation to former smokers, even in comparison with individuals who have had a long and intense history tobacco use. Considering this scenario, some drugs are used in tobacco cessation therapy. The first-line anti-smoking treatments approved by the Food and drug administration ( FDA ) are nicotinic reuptake therapy, bupropion ( norepinephrine and dopamine reuptake inhibitor) and varenicline ( partial agonist of nicotinic receptors composed of subunits alpha4Beta2 ). A metanalysis of 16 clinical studies indicated that smokers treated with bupropion had a higher abstinence rate compared to those receiving placebo - Odds ratio (OR ) - of 1,97 for treatment success. Varenicline is more effective compared to others smoking cessation drugs approved by the FDA, with an OR of 2,27 ( IC 95% 2,02-2,55 ) compared to placebo. However, Varenicline is much more expensive than bupropion. Significant advances in genetics have made the variability of the individual response to drugs, as far as efficacy as well as the rate of adverse effects, begin to be specifically investigated through pharmacogenetics studies.

This research is being done to develop the electronic platform Nest for young adults (ages 18-39) who have had prior cancer genetic testing. The platform will give patients and their clinicians access to continuously updated information about both pathogenic variants and variants of uncertain significance (VUS). The name of the intervention used in this research study is: Nest portal (electronic platform for patients and clinicians)

Aerobic exercise - Nordic walking in Persistent Covid (PC) vs. healthy controls. The main objective of this study is to analyse the genes associated with increased physical performance in patients with PC vs. healthy controls and to measure the level of lactic acid in blood, pre and post exercise session in patients affected by PC. Relevance: It is intended to be a tool for patients with CP who have not been hospitalised, nor have been offered outpatient rehabilitation treatment. They have not recovered their work, family, sporting or leisure functions. They have particular problems in returning to aerobic exercise. We think that they may need to be accompanied in the recovery of their physical condition under the supervision of health professionals. Most of the studies offered to them are exploratory, not intervention. Our proposal is a 12-week intervention. Our proposal, delves into the mechanisms that may underlie their fatigue and their problems in returning to aerobic exercise, in order to collaborate in approaching possible solutions. Secondary objectives: To study in each of the patients with persistent covid, included in the aerobic Nordic walking programme, their DNA in order to, based on two candidate genes, analyse the role of genetic polymorphisms associated with increased VO2 max training, compared to a healthy control group. To assess the blood lactic acid level pre and post exercise in a group of patients with persistent covid pre and post aerobic Nordic walking programme. Patients and Methods: 33 patients with CP and 33 healthy controls will follow a Nordic walking programme for 12 weeks. QIAGEN Cube automatic extractor and lactic acid meter will be used.

Phaeochromocytomas and paragangliomas (PPGLs) are tumours of the adrenal medulla and extra-adrenal sympathetic nervous system, some which can become metastatic. It is a very rare disease and the tumours are often detected late. Approximately 50 % of the tumours are caused by germline genetic variants screening programmes are recommended for patients and their family members; however, they are not yet well-targeted with respect to individual prognosis. In this study the investigatorscaim to characterize the genotype-phenotype associations in all Danish patients (n=400) diagnosed with PPGLs who have been followed in tertiary centres using medical records and national registries. To this end novel immunohistochemical, genetic, and epigenetic biomarkers in tumour tissues samples from biobank material (blood samples and tumour tissue) will be investigated to develop a comprehensive predictive algorithm for disease prognosis. The study will provide a clinical tool for an improved targeted screening program and subsequently prevention of disease development.

The purpose of this research study is to learn more about the inherited risk for developing lung cancer.

This is a clinical, epidemiologic, genetic, and laboratory study of individuals and families at high risk of cancer and selected tumors to investigate the genetic susceptibility and environmental exposures which may alter cancer risk. Families with multiple members who have an unusual pattern or number of cancers or tumors are evaluated clinically. This evaluation is specific for the type of cancer or tumor predominant in the family in order to determine the affection status of each individual for genetic epidemiologic studies. Genetic and environmental risk factor information specific for the tumor type is obtained. Individuals with, or at high risk of, cancer because of their personal, familial, or environmental histories are identified by healthcare worker referral or by personal inquiry. Relevant etiologic risk factor information is documented through review of pathology specimens and medical, vital, and genealogical records. Selected individuals and family members are asked to complete questionnaires and to undergo clinical evaluations specific for the tumor of interest. They are also asked to donate biologic specimens to be used in the search for cancer etiology and mechanisms of carcinogenesis. No therapy beyond counseling and education for cancer prevention, risk reduction, and early detection will be given. Genetic testing for tumor susceptibility gene(s) mutations and risk notification will be offered to study participants for whom a specific mutation predictive of disease has been identified in his/her family. This testing will only be offered when reasonable individual cancer risk estimates can be delivered, and only to those participants who choose to know their individual genetic status after appropriate education and counseling. The testing will be conducted exclusively in Clinical Laboratory Improvement Amendments (CLIA)-licensed laboratories. Genetic testing and risk notification are entirely optional and do not affect participation in other aspects of the protocol. A separate consent procedure and consent form will be used for genetic testing and risk notification related to these specific genes. Once enrolled, study participants are monitored prospectively for the development of outcomes of interest, typically by means of periodic mail or telephone contact. In selected instances, subjects may return to the Clinical Center periodically for study-specific follow-up examinations. Although we do not offer specific anti-cancer therapy as part of this protocol, we provide assistance to insure that study participants who require treatment for tumor-related problems that develop during the course of the study are referred to appropriate healthcare providers. We remain available to study participants and their healthcare providers for advice and consultation related to the management of familial cancer/tumor predisposition.