cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.58020/5tam-z580
title: Restoring Insulin Secretion - Adult Medication Study

description: Approximately 10 percent of Americans have diabetes and at least 33 percent of American adults are considered prediabetic.  The increasing loss of beta-cell function is one of the key factors in the pathogenesis of type 2 diabetes.  Over time, increased insulin resistance and beta-cell dysfunction can lead to serious health complications in diabetics.  Research efforts have begun to focus on the effects of certain interventions on insulin resistance and beta-cell function at the early stages of the disease.  The Restoring Insulin Secretion (RISE) Adult Medication Study was established to determine if pharmaceutical treatment could preserve or improve beta-cell function in adults with prediabetes or recent onset type 2 diabetes.

The RISE Adult Medication Study was a partially double-blind, placebo-controlled, four-arm clinical trial.  Study participants were randomized into four groups and received treatment for 12 months.  During the treatment period, the first group received Metformin alone; the second group received Glargine for three months, followed by Metformin for the remaining nine months; the third group received Liraglutide in combination with Metformin; and the fourth group was treated with placebo.  Following the 12-month treatment period, each group underwent treatment withdrawal for three months.  Insulin sensitivity and beta-cell function was evaluated at baseline, the end of the treatment period, and the end of the withdrawal period.
DOI: 10.58020/ytrv-a816
title: Restoring Insulin Secretion – Pediatric Medication Study

description: Although type 2 diabetes is more common in adults, there has been an increase in the number of children with the disease, primarily due to the obesity epidemic. As with adults, the decline of beta-cell function and insulin sensitivity are precursors of type 2 diabetes in children. There are several treatments for adults with type 2 diabetes, however insulin and metformin are the only approved treatments for children with type 2 diabetes. The purpose of the Restoring Insulin Secretion (RISE) Pediatric Medication Study was to determine whether metformin or insulin combined with metformin could be used to sustain or improve beta-cell function in children with prediabetes or recently diagnosed type 2 diabetes.

The RISE Pediatric Medication Study was a two-arm, multi-center clinical trial.  Study participants were enrolled at four recruitment centers and randomized into two treatment groups. The first group received metformin alone for 12 months. The second group received glargine, a man-made insulin, for three months followed by metformin for the remaining nine months of the treatment period. Beta-cell function and insulin sensitivity were assessed at baseline, the end of the active treatment period, and three months after treatment was withdrawn.
DOI: 10.58020/v6zz-1r31
title: Safety and Effectiveness of Low Molecular Weight Sulfated Dextran in Islet Transplantation

description: The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population is individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. CIT01 participants were randomized to study treatment including Low Molecular Weight Sulfated Dextran (LMW-DS) and study treatment without LMW-DS. Subjects in both arms received induction and maintenance immunosuppression consisting of ATG (basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable), etanercept, sirolimus, and tacrolimus. CIT01 subjects randomized to the LMW-DS arm also received LMW-DS before and during islet transplant.
DOI: 10.58020/axdh-3c73
title: Safety Study of Ornithine Phenylacetate to Treat Patients With Acute Liver Failure/Severe Acute Liver Injury

description: There is strong experimental and clinical rationale for the use of ammonia-lowering therapies in ALF. Ammonia is normally produced in the gut and transformed by the liver into urea. As the liver fails, ammonia increases in the systemic circulation and enters into the brain. The result of a rapid rise in ammonia or related compounds in the cerebral circulation is hepatic encephalopathy (HE), a reversible neuropsychiatric condition that ranges in severity from mild impairment in attention, to delirium, the development of cerebral edema, coma and death. This is a Phase 2a, multi-center, open-label study, conducted in two cohorts in patients diagnosed with acute liver failure/acute liver injury (ALF/ALI) who meet inclusion/exclusion criteria. 

This study is designed to provide data on OCR-002 with regards to the effect on circulating ammonia levels in patients with acute liver failure with and without impaired renal function at different doses after single and continuous infusion safety and dose tolerability as well as providing data on the metabolites, glutamine and phenylacetylglutamine in this patient population.

It is anticipated that this early efficacy, safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) and dose-ranging study will lead to a Phase 3 development program for the use of OCR-002 in the treatment of hyperammonemia due to ALF. No clinical outcome measures will be formally studied because of the small sample size.
DOI: 10.58020/4tqk-j164
title: SEARCH for Diabetes in Youth

description: The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000 to address major knowledge gaps in the understanding of childhood diabetes. The SEARCH study (SEARCH 1-3) was conducted at five sites across the U.S. and established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. The cohort study (SEARCH 4) was developed by recruiting incident cases in 2002 to 2006, 2008, and 2012 that had a baseline visit near diagnosis and at least 5 years of diabetes duration at the cohort visit assessment.  In the first two phases of SEARCH (SEARCH 1 and 2), individuals newly diagnosed with diabetes in 2002– 2006 and 2008 were recruited for a baseline research visit. Incident cases from 2002–2005 were also asked to return for visits at 12, 24, and 60 months after their baseline visit to measure risk factors for diabetes complications. In the third phase (SEARCH 3), a subset of SEARCH participants with a duration of diabetes >5 years were recruited for an outcome visit between 2011 and 2015. In addition, individuals incident in 2012 were invited for a baseline visit. In the fourth phase (SEARCH 4), a subset of SEARCH participants aged >10 years with at least 5 years of diabetes duration were invited to another study visit between 2015 and 2019. Those invited to the in-person research visit included all individuals with type 2 diabetes, all non-Whites, and a random sample of non-Hispanic Whites with type 1 diabetes.
DOI: 10.58020/p1s1-tv84
title: Silymarin Trial for Hepatitis C and NASH

description: The Silymarin Trial for Hepatitis C and NASH (SyNCH) is a randomized, double-masked, placebo-controlled phase II study that assessed the safety and efficacy of a standardized orally administered silymarin preparation (Legalon®) for the treatment of patients with chronic hepatitis C virus (HCV) who failed conventional antiviral therapy. The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease, despite scant and conflicting evidence of its efficacy. In light of inconclusive past clinical trials, the SyNCH study aimed to determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus (HCV). In the phase I trial, an initial dose-ranging study was performed to identify silymarin doses for further study. Two doses, 3 and 5 times higher than the customary dose, were selected for the phase II trial based on this early testing.

The study enrolled participants with chronic HCV infection and serum alanine aminotransferase (ALT) levels of at least 65 U/L who were previously unsuccessfully treated with interferon-based therapy were enrolled. Participants were randomly assigned to 1 of 3 groups: 420-mg silymarin, 700-mg silymarin, or matching placebo gelatin capsules administered 3 times daily for 24 weeks, a standard duration of treatment for which effective therapies for HCV have regularly demonstrated improvement in disease activity. The primary outcome measure for efficacy was serum ALT level of 45 U/L or less (approximate normal range) or attainment of at least 50% decline of ALT level to less than 65 U/L after the 24-week treatment period. 
Results showed that after 24 weeks of treatment, only 2 participants in each treatment group met the primary outcome measure: 3.8% for placebo, 4.0% for 420-mg silymarin, and 3.8% for 700-mg silymarin. Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy.
DOI: 10.58020/4dx3-7587
title: Steroids in the Treatment of Biliary Atresia

description: Biliary atresia is a condition in which the common hepatic bile duct becomes blocked, preventing bile drainage from the liver. Biliary atresia occurs in infants and requires portoenterostomy, a surgical procedure, in order to re-establish bile flow from the liver to the small intestine. Despite the surgical intervention, about half of the children will need a liver transplant before the age of five. The aim of the START study was to determine whether corticosteroid treatment after portoenterostomy would improve bile drainage and reduce the need for liver transplantation, compared to surgery alone. 

The START study participants were recruited from the ChiLDREN prospective observational database study and randomized into either the corticosteroid or placebo group within 72 hours after the portoenterostomy procedure. Patients were given their assigned treatments daily over the course of 13 weeks. After the treatment period, patients underwent follow-up testing and assessments until age 24 months.

The data package now includes analysis datasets (Bezerra) from a publication.
DOI: 10.58020/vpj2-xq84
title: Strategies to Improve Long Term Islet Graft Survival and Extended Follow Up after Islet Transplantation in Type 1 Diabetes

description: The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population was individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. The CIT02 protocol focused on treating islets pre-transplant, and subjects were randomized to receive islets prepared with either Lisofylline or Exenatide. For induction and maintenance immunosuppression, the subjects received rabbit anti-thymocyte globulin (ATG; basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable), etanercept, sirolimus, and tacrolimus in an open-label fashion.
DOI: 10.58020/0zjd-vz86
title: Symptoms of Lower Urinary Tract Dysfunction Phenotyping Study

description: Lower urinary tract dysfunction (LUTD) is a condition related to the functions and/or structures of the lower urinary tract.  LUTD affects both men and women, and becomes more common and frequent with age.  Patients tend to exhibit a range of lower urinary tract symptoms (LUTS), but there has been a lack of understanding regarding which biological and psychosocial factors cause the symptoms to manifest and worsen.  As a result, treatment and management methods for LUTS and LUTD have been unsatisfactory.  

The Symptoms of Lower Urinary Tract Dysfunction Phenotyping Study (LURN) was established to gain a better understanding of lower urinary tract symptoms in an effort to improve the lives of those with LUTD.  LURN participants were enrolled at multiple sites within the United States.  Patients were assigned to one of four subgroups, based on their symptoms, the outcomes of clinical assessments, and other characteristics.  Biological samples were collected from study participants and patients were required to complete certain assessments and examinations at standard time-points during the study period.
DOI: 10.58020/63vn-7d44
title: T1DGC HLA Reference Panel for Imputation with SNP2HLA

description: The [T1DGC Immunochip/HLA Reference Panel](http://www.ncbi.nlm.nih.gov/pubmed/23762245) (described in Jia et al., PLoS ONE 2013; Jun 6;8(6):e64683) enables accurate imputation of classical HLA types starting from SNP genotype data. Exploiting long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC) region, a computational strategy, called SNP2HLA, has been developed to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C) and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1) loci. A European ancestry reference panel was constructed based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals). For validation, HLA alleles were imputed in the British 1958 Birth Cohort (N = 918) with gold-standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500K and Illumina ImmunoChip microarrays. Using the T1DGC reference panel, the average accuracy at four-digit resolution is 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, accuracy was 99.3% using the Illumina ImmunoChip. A link to the SNP2HLA software via the Broad institute is located below. The T1DGC reference panel can be accessed by submitting a request from this page.

* [The SNP2HLA software package](http://www.broadinstitute.org/mpg/snp2hla/) 
* [T1DGC main study](/studies/t1dgc/) 

<b>Note: The panel may only be used for research in the areas of diabetes, autoimmune diseases and diabetes complications.</b>
DOI: 10.58020/db9d-0n41
title: Targeting INflammation using SALsalate for Type 2 Diabetes

description: The National Institutes of Health–sponsored TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) trials determine whether this generic and inexpensive drug is safe, tolerated, and efficacious in diabetes.  Stage 1 was a dose-ranging study whereas stage 2 of TINSAL-T2D is a larger study to assess the magnitude and durability of glycemic efficacy over 1 year, tolerability, and an array of safety variables relevant to patients with diabetes.

This trial evaluated glycemic effects of salicylate compared with placebo as add-on therapy for patients with inadequately treated, established T2DM.  Salicylate is one of the oldest drugs in clinical practice, with documented use of relevant plant extracts for treating pain and inflammation dating back at least 3500 years.  Nevertheless, its medicinal properties and mechanisms of action remain incompletely understood.  When salicylate is acetylated by chemists, it yields aspirin.   However, pure salicylate lacks an acetyl group and, thus, must have a different mechanism of action. Salicylate has not been tested previously for efficacy and safety under what regulatory agencies now consider to be current standard practice in clinical trials.
DOI: 10.58020/dzq8-ct80
title: The Chronic Kidney Disease in Children Cohort Study

description: Chronic kidney disease (CKD) is a life-long condition that often results in substantial morbidity and premature death due to complications from a progressive decrease in kidney function. The early detection of, and initiation of therapy for, CKD is key to delaying or preventing progression to end-stage renal disease (ESRD). The CKiD (Chronic Kidney Disease in Children, https://statepi.jhsph.edu/ckid/) study is a prospective cohort study of children with CKD that investigates risk factors and outcomes of the disease.

The study population consists of two cohorts. Cohort 1 includes 586 racially and ethnically diverse children recruited between the ages of 1 and 16 years with mild to moderately impaired kidney function (defined by an estimated GFR between 30-90 ml/min/1.73m<sup>2</sup>). Cohort 2 includes 305 children with mildly impaired kidney function (defined as an estimated GFR between 45-90 ml/min/1.73m<sup>2</sup>). At baseline, participants underwent a physical examination, in addition to assessments of kidney, cardiovascular, and neurocognitive symptoms and function. Similar measures of kidney function, neurocognitive function, markers of risk factors for cardiovascular disease, growth and other co-morbid conditions are assessed at regularly scheduled study visits. Biospecimens, including serum, plasma, and urine are also collected. The primary outcome measure is the rate of decline of GFR, which is measured repeatedly over time in cohort participants. A secondary outcome measure is the time to ESRD, defined by transplantation, dialysis, or a 50% decrease in GFR.

Baseline and follow-up biospecimens and data through July 31, 2018 are available from the Repository. The most recent data contains additional summary files related to nutrients and grip strength.
DOI: 10.58020/e4nx-6v60
title: The CKD Optimal Management With BInders and NicotinamidE

description: Phosphorus, a mineral found in many foods, works with calcium and vitamin D to keep bones healthy. Healthy kidneys keep the right balance of phosphorus in the body. Fibroblast growth factor 23 (FGF23) is a hormone that helps the kidneys to control the blood levels of phosphorus. 
 
In people with chronic kidney disease, kidneys struggle to get rid of enough phosphorus, so FGF23 levels increase in the blood to help get rid of extra phosphorus. Over time, with progressive loss of kidney function, both phosphorus and FGF23 can build up in the blood simultaneously. Researchers believe that too much phosphorus and FGF23 in the blood may lead to weak bones, increase the risk of heart problems, and accelerate progression of kidney disease. However, the best way to control phosphorus and FGF23 levels in the blood in patients with chronic kidney disease is not known.

COMBINE is a study to determine new methods to lower serum phosphorus levels and levels of FGF23 in chronic kidney disease patients.
DOI: 10.58020/1bv7-0y43
title: The Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects

description: Type 1 diabetes (T1D) is a chronic, slowly progressive autoimmune disease characterized by the destruction of β-cells in the pancreas. Although the presence of autoantibodies is a diagnostic criterion, the immunopathogenesis of β-cell destruction in T1D is typically associated with T-lymphocyte autoimmunity.  B lymphocytes play a crucial role as antigen-presenting cells in the mechanism of T lymphocyte activation. The Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects (TN05 antiCD20) is a randomized, placebo-controlled clinical trial that was established by TrialNet, a network of 18 clinical centers that conducts research on T1D, to test whether transient elimination of B lymphocytes with the anti-CD20 monoclonal antibody rituximab would decrease immune-mediated destruction of β-cells and thus preserve β-cell function in patients with T1D of recent onset. 

Patients between the ages of 8 and 45 years who had T1D were screened for the presence of at least one type of detectable diabetes autoantibody (microinsulin autoantibody, glutamic acid decarboxylase 65, islet-cell antigen 512, or islet-cell autoantibody). Eligible patients were randomized to treatment with rituximab via intravenous infusion or placebo. The primary outcome measure was the mean area under the curve (AUC) for the stimulated C-peptide response during the first 2 hours of a 4-hour mixed-meal tolerance test conducted at 12 months, with the response expressed in picomoles per milliliter. Safety outcome measures included infusion reactions (occurring within 24 hours after an infusion), infections, and laboratory assessments of white-cell counts and immunoglobulin levels. Patients were followed for an additional year after evaluation of the primary outcome at 12 months. 

Results showed that the mean AUC for the level of C peptide was significantly higher for the rituximab group than for the placebo group at 12 months. Additionally, the glycated hemoglobin level and the insulin dose were both significantly lower in the treatment group than in the placebo group. The group treated with rituximab showed higher rates of adverse events.  Findings support the hypothesis that B lymphocytes play a role in the pathogenesis of T1D and that therapy targeting B cells may have a beneficial effect on β-cell function in early T1D. While initial improvements in C-peptide levels following rituximab administration resumed decline after 12 months, treatment with other anti-B-lymphocyte agents may open a new pathway for exploration in the treatment of patients with this condition.