Dataset Information

Longitudinal Study of the Porphyrias

ABSTRACT:

This is an observational, longitudinal study of approximately 800 individuals with various types of porphyria. Those participants will be evaluated annually for 5 years, or longer if they agree.
Participation in this project will include:

Participating in annual visits or contacts.
Providing samples, including blood, buccal cells (cells from inside of the mouth), saliva, and urine. The type of samples and amounts may vary from person to person, depending on the type of porphyria.
Giving permission for samples to be stored and used for porphyrias research.
Granting permission to obtain your medical records.
Providing information about your medical history and family history.
Completing a questionnaire about your porphyria symptoms and quality of life.

PROVIDER: phs001278 | dbGaP |

SECONDARY ACCESSION(S): PRJNA369451PRJNA369452

REPOSITORIES: dbGaP

ACCESS DATA

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Project description:Reprinted from http://www.haltctrial.org/ Purpose The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial is a randomized controlled trial designed to evaluate the safety and efficacy of long-term use of pegylated interferon for the treatment of chronic hepatitis C in patients who failed to respond to previous interferon therapy. The HALT-C Trial was developed to determine whether prolonged interferon therapy altered histological and clinical outcomes in a group of patients who had failed to eradicate hepatitis C virus with previous interferon treatment. Study Hypotheses <ol> <li>In patients with chronic hepatitis C and bridging fibrosis who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can prevent progression to cirrhosis.</li> <li>In patients with cirrhosis secondary to chronic hepatitis C who failed to eradicate the virus with previous interferon therapy, long-term treatment with interferon is safe and can reduce the risks of hepatic decompensation or of hepatocellular carcinoma.</li> </ol> Study Design 1145 patients with chronic HCV and advanced hepatic fibrosis (Ishak stage 3-6) who failed to respond to previous treatment with interferon were enrolled at 10 clinical centers and entered into a Lead-in phase. They were treated with a combination of pegylated interferon (Pegasys®, Hoffmann-La Roche) 180 µg/week and ribavirin (1000-1200 mg/day) for 24 weeks. Patients who had no detectable HCV-RNA at week 20 continued on combination therapy until week 48. 662 patients who did not clear virus were randomly assigned at week 24 to either continue treatment with pegylated interferon alone (90 µg/week) for an additional 42 months, or to have treatment discontinued. All patients were followed at 3-month intervals following randomization. Liver biopsy was performed at baseline and after 1.5 and 3.5 years of treatment. Because of slower than expected enrollment and the approval by the FDA of peginterferon alfa-2b after the start of the trial, we modified the study protocol in three ways. First, criteria for admission to the trial were liberalized to allow patients to enter the trial with lower platelet and white blood cell counts than had been initially considered safe or tolerable. Second, 151 Lead-in patients and those continuing on therapy after 24 weeks who demonstrated return of viremia during or after their 48-week treatment period (called "Breakthrough" or "Relapse" patients, respectively) were allowed to return to enter the randomized trial. Third, 237 patients treated with peginterferon alfa-2b (or with peginterferon alfa-2a in licensing trials) outside the HALT-C Trial who in other respects met all study criteria, having received the equivalent of Trial Lead-in period therapy, were allowed to enter the long-term trial as "Express" patients. A total 1050 patients were randomized. Those patients who completed Month 48 were offered an "extended follow-up (observation only)" until October 2009. These visits will primarily be to identify outcome events, and to provide information to patients concerning the current status of the trial. Some questionnaires, blood tests, and an ultrasonogram will be performed. Quarterly (every 3 months) <ul> <li>Interval history of complications, adverse events</li> <li>Current medications</li> <li>Brief physical examination</li> <li>Laboratory tests: liver panel, CBC, INR, AFP</li> <li>Child-Pugh Score</li> <li>Stored serum</li> </ul> Annual <ul> <li>Complete physical examination</li> <li>Ultrasound of liver</li> </ul> 1.5 years (M24 visit, middle of study) <ul> <li>Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)</li> </ul> 3.5 years (M48, end of study) <ul> <li>Liver biopsy: formalin fixed histology, frozen liver tissue (subset of patients)</li> <li>Endoscopy: evaluate esophageal varices and portal hypertension</li> </ul> After Month 48 <ul> <li>Observation only (no treatment) to determine clinical outcomes</li> <li>Clinic visit every 6 months with current medications, brief PE, liver panel, CBC, AFP, stored</li> <li>Serum</li> <li>Ultrasound of liver every 6 months</li> </ul> Outcome Variables Primary outcome variables to be assessed in the two groups of patients include: <ul> <li>Development of cirrhosis on liver biopsy (progression of Ishak fibrosis score by 2 points or more)</li> <li>Development of hepatic decompensation, as shown by:</li> <ul> <li>Sustained increase in the Child-Turcotte-Pugh score to 7 points or higher</li> <li>Variceal hemorrhage</li> <li>Ascites</li> <li>Spontaneous bacterial peritonitis</li> <li>Hepatic encephalopathy</li> <li>Development of hepatocellular carcinoma</li> <li>Death</li> </ul> </ul> Secondary outcomes include quality of life, serious adverse events, events requiring dose reductions, and development of presumed hepatocellular carcinoma.

Project description:Genome-wide DNA methylation profile of human spermatozoa using the meDIP technique and massively parallel sequencing. DNA methylation is an indispensible epigenetic modification required for regulating the expression of mammalian genomes. Immunoprecipitation-based methods for DNA methylome analysis are rapidly shifting the bottleneck in this field from data generation to data analysis, necessitating the development of better analytical tools. In particular, an inability to estimate absolute methylation levels remains a major analytical difficulty associated with immunoprecipitation-based DNA methylation profiling. To address this issue, we developed a cross-platform algorithm-Bayesian tool for methylation analysis (Batman)-for analyzing methylated DNA immunoprecipitation (MeDIP) profiles generated using oligonucleotide arrays (MeDIP-chip) or next-generation sequencing (MeDIP-seq). We developed the latter approach to provide a high-resolution whole-genome DNA methylation profile (DNA methylome) of a mammalian genome. Strong correlation of our data, obtained using mature human spermatozoa, with those obtained using bisulfite sequencing suggest that combining MeDIP-seq or MeDIP-chip with Batman provides a robust, quantitative and cost-effective functional genomic strategy for elucidating the function of DNA methylation. ArrayExpress Release Date: 2008-06-10 Publication Title: A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis Publication Author List: Thomas A Down; Vardhman K Rakyan; Daniel J Turner; Paul Flicek; Heng Li; Eugene Kulesha; Stefan GrÃ¤f; Nathan Johnson; Javier Herrero; Eleni M Tomazou; Natalie P Thorne; Liselotte BÃ¤ckdahl; Marlis Herberth; Kevin L Howe; David K Jackson; Marcos M Miretti; John C Marioni; Ewan Birney; Tim J P Hubbard; Richard Durbin; Simon TavarÃ©; Stephan Beck Person Roles: submitter; investigator Person Last Name: Flicek Person First Name: Paul Person Mid Initial Person Email: flicek@ebi.ac.uk Person Address: Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK Person Affiliation: European Bioinformatics Institute