cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.58020/h3m1-z998
title: The Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment

description: Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of the disease, which results in cirrhosis, liver failure, and death in a substantial proportion of patients. Treatment approaches to NAFLD in adults and children target reduction in insulin resistance and oxidative stress. Several agents have been found to be promising as therapy of NAFLD in small clinical trials, but none have been proven to alter its natural history or outcome, and none are approved for general use in this disorder.  The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was established by the NIDDK in 2002 to investigate the natural history, pathogenesis, and therapy of NAFLD and NASH in both children and adults. The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis (NASH) Treatment (FLINT) trial was a multicenter, randomized, placebo-controlled clinical trial conducted by the NASH CRN to investigate the safety and efficacy of treatment of obeticholic acid compared to placebo in adults with nonalcoholic fatty liver disease.

Individuals with histologic evidence of NASH, based on a liver biopsy and a disease activity score (NAS) of at least 4 (with a score of at least 1 in each component of the NAS 8-point scale), were enrolled and randomized to treatment with either obeticholic acid (25 mg) or placebo for 72 weeks. Each participant received a baseline oral glucose tolerance test and a baseline MRI scan to determine liver fat content. Additionally, information was collected on demographics, alcohol consumption, and medication use. The primary outcome measure was improvement in the NAS score by at least 2 points with no worsening of liver fibrosis and was assessed by liver biopsy at 72 weeks. Secondary outcome measures included change in NASH diagnosis (from determinate or indeterminate to not-NASH), fibrosis score, hepatocellular ballooning score, hepatic fat fraction, serum aminotransferase and gamma-glutamyl transpeptidase (GGT) levels, fasting glucose levels, and health related quality of life scores.

A planned interim analysis of end-of-treatment liver biopsies from 58% (164/283) of enrolled patient demonstrated that the primary endpoint had been reached and the statistical significance crossed the preset boundry set for efficacy (p ≤ 0.0031). Accordingly, further liver biopsies were not performed. Additionally, because of the observation of disproportionate lipid abnormalities among patients receiving OCA and in the context of the study having met its primary endpoint, further treatment with OCA and placebo was discontinued and remaining patients completed a 24-week follow-up off treatment.
DOI: 10.58020/vj89-zr33
title: The Genetics of Kidneys in Diabetes

description: The Genetics of Kidneys in Diabetes (GoKinD) study was an initiative that aimed to identify genes that are involved in diabetic nephropathy. A large number of individuals with type 1 diabetes were screened to identify two subsets, one with clear-cut kidney disease and another with normal renal status despite long-term diabetes. Those who met additional entry criteria and consented to participate were enrolled. When possible, both parents also were enrolled to form family trios. DNA, serum, plasma, and urine samples and clinical information were collected from participants. A repository of genetic and clinical information was created for use in genetic analysis to investigate the genetic risk factors of the renal disease of Type 1 diabetes, with the ultimate aim of determining pathways for intervention to prevent diabetic kidney disease and allow targeting of preventive therapies.

GWAS data must be requested through dbGAP.
DOI: 10.58020/d1m7-ye92
title: The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial

description: The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C) is a randomized clinical trial of long-term use of peginterferon alfa-2a in patients with chronic hepatitis C. The study investigated whether long-term antiviral therapy could prevent progressive liver disease—including cirrhosis, liver failure, hepatocellular carcinoma, and death—in chronic hepatitis C patients. Patients with chronic hepatitis C and advanced fibrosis who failed to respond to prior treatment with peginterferon and ribavirin were enrolled in the study. The participants, who were stratified according to stage of fibrosis, were randomly assigned to receive either peginterferon or no therapy for 3.5 years. The primary outcome measure was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Results showed that the level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly with treatment, but there was no significant difference between the groups in the rate of disease progression.

Some of the patients with hepatitis C-related advanced liver disease developed hepatocellular carcinoma (HCC), and there is an existing matched set of samples from these patients and controls. Please see the <a href="https://repository.niddk.nih.gov/studies/halt-c/HCC_Documents/">HCC Documents</a> link to download the documents detailing the description of this set of samples and guidelines for its use in validating serum biomarkers. Investigators interested in using this set should make sure to refer to it specifically in their requests.
DOI: 10.58020/ryre-f394
title: The Stress Incontinence Surgical Treatment Efficacy Trial

description: Among women with urinary incontinence, 50 to 80% are identified as having stress urinary incontinence (SUI), or involuntary leakage of urine resulting from physical exertion, sneezing, or coughing. The Burch colposuspension and the autologous rectus fascial sling are two surgical procedures frequently used to treat SUI. Both procedures are believed to have similar “cure” rates, yet have not been compared directly to each other in a large, randomized clinical trial. The Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) is a multicenter, randomized study that was conducted to compare the efficacy and safety of the sling and Burch procedures. Complications, quality of life, sexual function, patient satisfaction, costs, and the need for additional treatments or surgery were also compared for the two procedures as secondary objectives. 

Women with documented symptoms of SUI for at least 3 months and a positive standardized urinary stress test who were planning to undergo surgery as treatment were enrolled and randomly assigned in the operating room to either a sling or Burch procedure. Key elements of the two surgical procedures were standardized among all clinical centers and participating surgeons. Data were collected preoperatively and postoperatively and included information on demographics, risk factors for urinary incontinence, clinical characteristics of urinary incontinence, findings on physical examination, and urodynamic evaluation. The two primary outcome measures consisted of composite measures of success of treatment in both overall urinary incontinence and specific stress incontinence. 

Results showed that the pubovaginal fascial sling had significantly higher rates of success for both overall and stress-specific incontinence than did the Burch colposuspension in women with predominant SI at 24 months. Additionally, the frequency of surgical retreatment for SI was greater in the Burch group than in the sling group, although these higher success rates were offset by increased morbidity in the sling group.  

Data from the E-SISTEr 5 year follow-up are now included in the data package.
DOI: 10.58020/jak2-r752
title: The Study of Tamsulosin for Urolithiasis in the Emergency Department

description: The Study of Tamsulosin for Urolithiasis in the Emergency Department (STONE) was initiated at a single site with 109 participants who were randomized from 2008 to 2009. This first phase allowed an assessment of the feasibility of recruitment and provided the opportunity to determine the rate of stone passage in the placebo group. The primary outcome was not analyzed at the end of phase 1. The second phase of the study was conducted from 2013 to 2016 at 6 emergency department recruiting sites, including the original site in phase 1. The data from participants enrolled in both phases were analyzed together.

Eligible patients were randomized to either tamsulosin at a dose of 0.4 mg daily or a matching placebo in a 1:1 allocation. Both treatments consisted of identically encapsulated pills with identical packaging (1 bottle with 30 capsules per patient). Neither the participant nor the study staff knew to which group the participant was randomized. The randomization sequence was generated using the simple urn method, stratified by site. Study participants were contacted by telephone to collect data at 2, 7, 15, 20, 29, and 90 days after randomization. Study participants enrolled in the second phase were also asked to undergo a follow-up CT scan after the 28-day treatment period to determine whether their stone had passed based on this imaging modality.
DOI: 10.58020/q43e-6489
title: Time to Reduce Mortality in End-Stage Renal Disease

description: The TiME trial was a cluster-randomized, parallel-group pragmatic clinical trial for patients initiating treatment with maintenance hemodialysis. Facilities were randomized in a 1:1 distribution to the Intervention arm or the Usual Care arm. The facilities randomized to the Intervention arm adopted the practice of recommending dialysis session durations of at least 4.25 hours for all patients, while the facilities randomized to the Usual Care arm maintained their existing recommendations for dialysis session durations. The TiME trial follow-up lasted 3 years where the primary endpoint was mortality and secondary endpoints included hospitalization and quality of life. Features of the TiME trial included high generalizability due to non-restrictive eligibility criteria, implementation of the intervention by clinical care providers instead of research personnel, and data collection conducted through routine clinical care rather than through research activities.
DOI: 10.58020/vwa2-e568
title: TN10 Anti-CD3 Prevention

description: Up to ten percent of all diagnosed diabetics have type 1 diabetes. Type 1 diabetes is a condition that develops due to an autoimmune attack against beta cells in the pancreas, which causes the body to stop producing insulin. Occurring most often in children and young adults, this type of diabetes appears suddenly and can lead to lifelong health complications. Relatives of people with type 1 diabetes have a greater risk of developing the disease. Type 1 Diabetes TrialNet is an international clinical trials network sponsored by NIH which conducts studies to find ways to prevent or delay the development of the disease and to enhance treatment for the newly diagnosed. 

Teplizumab (Anti-CD3) is a monoclonal antibody that interferes in the autoimmune attack of pancreatic beta cells. Previous studies have shown that teplizumab reduces the loss of insulin production in type 1 diabetics during the first year after diagnosis. TrialNet 10 is a phase 2 prevention trial of TrialNet, studying the effect of teplizumab on insulin production in the relatives of type 1 diabetics who are at high risk of developing the disease. TrialNet 10 is projected to last 4-6 years with an enrollment period of 2-3 years. The approximate enrollment of the study is 140-170 individuals between the ages of 8-45 years. Subjects will be randomly assigned to either the active or placebo group of the study, and monitored and tested over time until diagnosed with diabetes.
DOI: 10.58020/pr1r-5t62
title: TODAY2 Control Echocardiogram Sample Data Collection Study

description: The TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study was a multi-center randomized clinical trial (2004-2011). Youth aged 10-17 years diagnosed with type 2 diabetes (T2D) for less than 2 years were enrolled. The trial compared the efficacy of three treatment arms: (1) metformin alone, (2) metformin plus rosiglitazone, and (3) metformin plus an intensive lifestyle intervention. The TODAY trial concluded in February 2011 and was followed by TODAY2 (2011-2020), an observational longitudinal study to continue follow-up of the TODAY cohort to document the progression of diabetes and its complications and related comorbidities. 

In the last year of the TODAY study, the cohort was assessed by echocardiography. A follow-up echocardiogram was completed 5 years later during the TODAY2 study. During TODAY2, the study also collected comparative echocardiogram control data in individuals without diabetes and hypertension, and also performed a one-time collection of data and blood for storage of serum and plasma in these consented control participants.
DOI: 10.58020/a35t-am89
title: TODAY Genetics Study

description: The rise in childhood obesity has been accompanied by an increased prevalence of type 2 diabetes (T2D) mellitus in children and adolescents. Research has shown the importance of adequate treatment and management on the vascular disease progression of T2D in adults, but research on the treatment and clinical course of T2D in youth has been limited. The TODAY (Treatment Options for Type 2 Diabetes in Adolescents & Youth) study was a 3-arm, prospective, randomized, partially blinded clinical trial of treatment for adolescents diagnosed with T2D.

The TODAY Genetics study was an ancillary study of the TODAY interventional trial conducted under the auspices of the TODAY study group. 

Individuals diagnosed with T2D before the age of 18 and had BMI ≥ 85th percentile were recruited from TODAY clinical centers and collaborators. Once enrolled, participants were asked to provide a one-time blood sample collection for analysis of diabetes type and DNA extraction. Information on participant and family medical history was also collected.

Note: Given that the TODAY Genetics study was an extension of the main TODAY study, any requestors interested in TODAY Genetics are strongly encouraged to review the TODAY study (https://repository.niddk.nih.gov/studies/today/).
DOI: 10.58020/m30b-w253
title: Treatment of Nonalcoholic Fatty Liver Disease in Children

description: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological diagnosis in which more than 5% of hepatocytes demonstrate macrovesicular steatosis in an individual without significant history of alcohol intake. NAFLD has become the most common cause of chronic liver disease in children in the United States, and encompasses a range of severity from bland steatosis to nonalcoholic steatohepatitis (NASH) that may ultimately result in advanced fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD was selected as the histologic entry criterion for this study because of a lack of knowledge about the natural history in the pediatric subset.<br><br>Treatment approaches to NAFLD in adults and children target reduction in insulin resistance and oxidative stress. Based on pediatric pilot data demonstrating potential efficacy of metformin or vitamin E, the NASH Clinical Research Network (NASH CRN), initiated a phase 3, multicenter, randomized, double-blinded, placebo-controlled trial evaluating vitamin E or metformin for the Treatment of NAFLD in Children (TONIC). The purpose of this study was to determine if therapeutic modification of insulin resistance or oxidative stress leads to improvement in serum or histologic indicators of liver injury or quality of life.<br><br>173 eligible patients were randomized in permuted blocks of treatments stratified by clinical center. Patients were assigned in a 1:1:1 ratio to 1 of 3 groups for 96 weeks of treatment, either (1) oral metformin (500 mg twice daily) and vitamin E placebo twice daily, (2) vitamin E (400 IU twice daily) and metformin placebo twice daily, or (3) vitamin E placebo and metformin placebo, each twice daily. 

The complete TONIC data is now available.
DOI: 10.58020/2w6w-pv88
title: Treatment Options for Type 2 Diabetes in Adolescents & Youth

description: Increases in childhood obesity have been accompanied by an increased prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents. Research has shown the importance of adequate treatment and management on the vascular disease progression of T2DM in adults, but research on the treatment and clinical course of T2DM in youth has been limited. the TODAY (Treatment Options for Type 2 Diabetes in Adolescents & Youth) study, was a randomized clinical trial of treatment for adolescents diagnosed with T2DM.

The TODAY study tested the hypothesis that an aggressive approach to reducing insulin resistance early in the course of T2DM would prolong glycemic control and improve associated risk factors. The trial consisted of three treatment arms: metformin alone, metformin with rosiglitazone, and metformin with an intensive lifestyle intervention program (called the TODAY Lifestyle Program or TLP). Individuals between 10 and 17 years old with a diagnosis of T2DM for less than two years, a body mass index (BMI) ≥ 85th percentile, and an absence of diabetes-related autoimmunity were eligible for the study. Upon enrollment, participants entered a run-in period of 2 to 6 months, with the goals of weaning them from non-study diabetes medications, initiating treatment with metformin, providing standard diabetes education, and documenting adherence to the medication regimen. Participants were required to attain glycemic control, defined as a glycated hemoglobin level of less than 8% and measured monthly for at least 2 months, with metformin alone before proceeding. Following successful completion of the run-in period, participants were randomized to treatment with metformin and either placebo or rosiglitazone as appropriate. For those assigned to treatment with the TLP, the program was delivered in a series of in-person visits and focused on weight loss through family-based changes in eating and activity behaviors. The primary outcome measure compared between groups was time to treatment failure, defined as a persistently elevated glycated hemoglobin level (≥8%) over a period of 6 months or persistent metabolic decompensation (defined as either the inability to wean the participant from insulin within 3 months after its initiation for decompensation or the occurrence of a second episode of decompensation within 3 months after discontinuation of insulin).

Results showed rates of failure of 51.7% (120 of 232 participants) for metformin alone, 38.6% (90 of 233) for metformin plus rosiglitazone, and 46.6% (109 of 234) for metformin plus lifestyle intervention. The study found that metformin with the addition of rosiglitazone, but not the intervention program, was superior to metformin alone.
DOI: 10.58020/z6n1-wc73
title: Treatment Options for Type 2 Diabetes in Adolescents & Youth Long Term Follow-Up

description: The TODAY2 study was a longitudinal follow-up study to the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study that continued the care and observation of the TODAY cohort participants beyond the end of the TODAY intervention trial. The TODAY2 study had two phases: 1) Transition of TODAY participants to non-blinded, non-randomized standard diabetes care and management with monitoring and follow-up for up to 24 months, and 2) Long-term longitudinal follow-up of the TODAY cohort based on findings from TODAY.
DOI: 10.58020/fpry-c314
title: TrialNet 06: Nutritional Intervention to Prevent (NIP) Type 1 Diabetes Pilot Trial

description: Type 1 diabetes (T1D) is a common childhood disease caused by islet cell autoimmunity.  Reports suggest omega-3 fatty acids may decrease the risk of T1D by suppressing the inflammatory immune responses that initiate the process of islet autoimmunity.  Various epidemiological studies and observations have concluded that the intake of omega-3 fatty acids is associated with a decreased risk of the development of T1D in children with an increased genetic risk for the disease.  

The TrialNet 06 study hypothesized that islet autoimmunity could be prevented in infants, with an increased risk for T1D, through the consumption of DHA, an omega-3 fatty acid.  Participants were enrolled during pregnancy or after birth, and randomized into the treatment or control group.  During the study, subjects in the treatment group received a vegetarian DHA substance while those in the control group received a placebo.  Treatments were administered daily for at least 36 months from the date of birth or the date of randomization.  Participants were regularly tested for DHA and inflammatory cytokine levels.  Additionally, TrialNet 06 was used as a pilot trial in order to determine the feasibility of a full-scale DHA supplementation study.
DOI: 10.58020/3wjj-nb81
title: TrialNet 08: Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of Type 1 Diabetes in New Onset Subjects

description: This multicenter, double-masked, randomized, controlled trial evaluated whether treatment of with a target antigen (glutamic acid decarboxylase) could modulate aggressive autoimmunity effects in subjects recently diagnosed with type 1 diabetes mellitus. Subjects were randomized via a 1:1:1 ratio into one of three treatment groups: three injections of 20 μg GAD-alum, two injections of GAD-alum and one of aluminum hydroxide alone (placebo), or three injections of aluminum hydroxide. These subcutaneous injections were completed at baseline, four weeks, and twelve weeks. All subjects received intensive diabetes management with the goal of achieving excellent glycemic control. Stimulated C-peptide levels were measured at the year 1 visit via a mixed meal tolerance test (MMTT). Subjects continued follow up for a second year including the performance of a MMTT every 6 months.
DOI: 10.58020/8nsj-w073
title: TrialNet 09: Effects of CTLA-4 IG (Abatacept) on the Progression of Type 1 Diabetes in New Onset Subjects

description: The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. Therefore, this multicenter, double-blind, randomized, controlled trial evaluated the effect of abatacept in subjects with recently diagnosed type 1 diabetes mellitus. Subjects were randomly assigned in a 2:1 ratio to receive either the experimental treatment of 30 minute intravenous infusion of 10 mg/kg of CTLA-4 Ig (abatacept) or an intravenous saline solution (placebo). The treatments were administered on days 1, 14, 28, and then every 28 days for a total of 27 doses over 700 days. All subjects received intensive diabetes management with the goal of achieving excellent glycemic control. 2 hour mixed meal tolerance tests (MMTT) were performed at 3, 6, 12 and 18 months. Four hour MMTTs were performed at baseline and at 24 months. Safety and efficacy were assessed over a two year follow-up period.