cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.58020/mn8k-ms49
title: Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications

description: The Diabetes Control and Complications Trial (DCCT) was a multicenter, randomized clinical trial designed to compare intensive with conventional diabetes therapy with regard to their effects on the development and progression of the early vascular and neurologic complications of type 1 insulin-dependent diabetes mellitus. The DCCT study involved 1,441 participants, ages 13 to 39, with type 1 diabetes and either no or minimal background retinopathy. Participants were required to have had diabetes for at least 1 year but no longer than 15 years.

Once enrolled, patients were randomized to receive standard therapy, consisting of not more than two injections of insulin per day, or intensive therapy, consisting of either subcutaneous insulin infusion by pump or at least three subcutaneous injections of insulin daily, targeting near-normal glycemia. Both groups received the same dietary management and education program. Blood glucose and hemoglobin A1c measurements were used as primary indicators of metabolic control. The primary outcome measure was diabetic retinopathy. Other outcome measures included diabetic nephropathy, diabetic neuropathy, and cardiovascular events or their known or putative risk factors. The DCCT study found that intensive therapy showed beneficial effects on retinopathy, nephropathy, and neuropathy when compared with conventional therapy.

Following these findings, the Epidemiology of Diabetes Interventions and Complications (EDIC) study was initiated as follow-up to examine the long-term effects of the original DCCT interventions on diabetic complications such as cardiovascular events and advanced retinal and renal disease. Over 90 percent of participants from the DCCT study were followed by the EDIC study. Similar to the DCCT study, glycosylated hemoglobin values, fasting lipid levels, serum creatinine values, and other risk factors for cardiovascular disease were measured at different intervals for participants. Cardiovascular complications were assessed with standardized means and classified by an independent committee. The EDIC study has found that intensive diabetes therapy reduced risk of cardiovascular disease in patients with type 1 diabetes and that the differences in outcomes between the intensive and conventional therapy groups persist after long-term study.

Data from the DCCT/EDIC study up to June 2017 (the end of EDIC Year 24) are available from the Repository. GWAS data may be requested through dbGAP.
DOI: 10.58020/3hw5-cf91
title: Diabetes Prevention Program

description: The Diabetes Prevention Program (DPP) is a clinical trial that investigated whether modest weight loss through dietary changes and increased physical activity or treatment with the oral diabetes drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in high risk individuals with prediabetes.

The study enrolled overweight persons with elevated fasting and post-load plasma glucose concentrations. Participants were randomized to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The primary outcome measure was development of diabetes, diagnosed on the basis of an annual oral glucose-tolerance test or a semiannual fasting plasma glucose test, according to the 1997 criteria of the American Diabetes Association: a value for plasma glucose of 126 mg per deciliter (7.0 mmol per liter) or higher in the fasting state, or 200 mg per deciliter (11.1 mmol per liter) or higher two hours after a 75-g oral glucose load. Participation in DPP continued after a diagnosis of diabetes was made, although study medication was discontinued and participants were sent to their local primary care provider for treatment of diabetes once fasting glucose was > 140 mg/dl.

Results showed that both lifestyle changes and treatment with metformin reduced the incidence of diabetes in persons at high risk compared with placebo. Furthermore, the lifestyle intervention was more effective than metformin in preventing the onset of diabetes.

Supplemental measurements were collected using biospecimens that were obtained during the original DPP clinical trial. These measurements included antibodies, biomarkers, hormones, and vitamin D levels to assess the relationships between sex hormones, diabetes risk factors, and the progression to diabetes. The supplemental data showed that sex hormones were associated with diabetes risk in men, but these associations were not found in women. Furthermore, obesity and glycemia were more important predictors of diabetes risk than sex hormones.
DOI: 10.58020/66x5-8y21
title: Diabetes Prevention Program Outcomes Study

description: The Diabetes Prevention Program (DPP) was a multicenter trial examining the ability of an intensive lifestyle program or treatment with metformin to prevent or delay the development of type 2 diabetes in high risk individuals with prediabetes. The DPP study showed that both interventions reduced the incidence of diabetes in participants, compared with placebo; the lifestyle intervention proved more effective than metformin in preventing the onset of diabetes. The Diabetes Prevention Program Outcomes Study (DPPOS) is the long-term follow-up of the original DPP study. The DPPOS study sought to evaluate the effects of the interventions on the further development of diabetes and diabetes complications, including retinopathy, microangiopathy, and cardiovascular disease.
 
All active DPP participants were eligible for continued follow-up, and 88% of DPP participants enrolled in DPPOS (910 participants from the lifestyle, 924 from the metformin, and 932 from the original placebo groups). On the basis of the benefits from the intensive lifestyle intervention in the DPP, all three groups were offered group-implemented lifestyle intervention. Placebo was discontinued in the placebo group, metformin treatment was continued in the original metformin group, with participants unmasked to assignment, and the original lifestyle intervention group was offered additional lifestyle support. Comprehensive annual and semi-annual assessments similar to those done in the DPP study continued in DPPOS and included physical measurements, medical history updates, adverse event assessment, medication adherence and dispensing, questionnaires, and an annual oral glucose tolerance test (OGTT). OGTTs were discontinued after a confirmed diagnosis of diabetes.
 
The study found that prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years; the cumulative incidence of diabetes remained lowest in the lifestyle group.

Data collected after the final DPP Bridge visits in 2002 through January 2014 are available from the Repository.
DOI: 10.58020/5njz-sc54
title: Diabetes Prevention Trial of Type 1 Diabetes

description: The Diabetes Prevention Trial—Type 1 Diabetes (DPT-1) consisted of two randomized clinical trials to determine whether insulin could prevent or delay the onset of overt diabetes in relatives of patients with diabetes. One study investigated the effects of parenteral insulin in relatives with a projected five-year risk of diabetes higher than 50 percent, while the other looked at the effects of oral insulin in relatives with a projected five-year risk of 26 to 50 percent.
 
First and second-degree relatives were screened for islet-cell antibody (ICA) titer ≥ 10 and then staged to assess risk of diabetes. Those with a high risk were eligible for the parenteral insulin trial, and those with a low risk were eligible for the oral insulin trial. In the parenteral insulin trial, subjects in the intervention group received parenteral insulin subcutaneous injections twice daily, plus annual intravenous infusions; the control group received no treatment. In the oral insulin trial, subjects were assigned to receive capsules of either oral insulin or matched placebo. For both trials, participants were seen every 6 months, and at those visits an oral glucose tolerance (OGT) test was performed to assess glycemic status, the primary study end point. Other assessments included intravenous glucose tolerance tests and mixed-meal tolerance tests performed at baseline, as well as at various points during the study. Results showed that neither parenteral nor oral insulin succeeded in delaying or preventing the development of diabetes in high-risk relatives of current diabetes patients. Long-term follow-up to detect any effects on the course of diabetes was initiated.
DOI: 10.58020/mp1g-4b68
title: Dialysis Access Consortium GRAFT

description: The Dialysis Access Consortium (DAC) was developed to investigate interventions to improve hemodialysis vascular access outcomes in patients with end-stage renal disease (ESRD). The Aggrenox Prevention of Access Stenosis Study (GRAFT) was one of two major clinical trials conducted under the DAC.  Surgically created arteriovenous (AV) grafts are the most common type of hemodialysis vascular access in the United States, but fail frequently due to the development of venous stenosis. The GRAFT study was a double-blind, placebo-controlled randomized clinical trial designed to test whether treatment with Aggrenox (dipyridamole and low-dose aspirin) prolonged the primary unassisted patency of newly placed grafts. Participants undergoing placement of a new AV graft for hemodialysis were randomly assigned to receive treatment with Aggrenox or placebo immediately following access surgery. The primary outcome measure was loss of primary unassisted patency, defined as the time from access placement until thrombosis or requirement for intervention to maintain or restore patency. Major secondary outcome measures included cumulative access failure and death. The GRAFT study found that treatment with Aggrenox had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts.
DOI: 10.58020/rs4w-6k77
title: DILIN: Prospective

description: The Drug-Induced Liver Injury Network (DILIN) was established in 2003 as a cooperative agreement among the National Institutes of Health, 5 academic clinical centers, and a data coordinating center. A major emphasis of DILIN has been to establish a protocol for the identification and enrollment of patients with clinically significant DILI into a prospective observational study and to create a registry and specimen repository of biological samples that could be used for mechanistic studies on the etiology and prevention of DILI. <br><br>The DILIN prospective study is an ongoing multicenter observational study. Patients (2 years of age or older) were enrolled in this study if there was a strong clinical suspicion that a liver injury event was caused by a medication or an herbal agent occurring within 6 months before enrollment. Additionally, patients must meet one of the biochemical criteria for enrollment into this study. 

Data from the DILIN Prospective study through the grant 3 cycle (2018) are available from the Repository.
DOI: 10.58020/2v81-5f48
title: DILIN: Retrospective

description: Drug-induced liver injury (DILI) is the single most common reason for regulatory actions concerning drugs, including failure to gain approval for marketing, removal from the market place, and restriction of prescribing indications. DILI is also a significant cause of morbidity and mortality in many patient populations. To stimulate and facilitate research into DILI, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has recently established the Drug-Induced Liver Injury Network (DILIN). One of the initial projects to be conducted by the network is to retrospectively establish a nationwide registry of patients who have suffered severe idiosyncratic liver injury associated with drugs (ILIAD), and to collect, and store serum, DNA from these patients (hereafter referred to as the “ILIAD protocol”). This ILIAD protocol will serve as a resource for subsequent mechanistic investigations of the basis for susceptibility to severe idiosyncratic DILI. 

Data from the DILIN Retrospective study through the grant 3 cycle (2018) are available from the Repository.
DOI: 10.58020/vxr2-3131
title: Effect of Clopidogrel on Early Failure of Arteriovenous Fistulas for Hemodialysis

description: The Dialysis Access Consortium (DAC) was developed to investigate interventions to improve hemodialysis vascular access outcomes in patients with end-stage renal disease (ESRD). The Clopidogrel Prevention of Early AV Fistula Thrombosis (FISTULA) study was one of two major clinical trials conducted under the DAC.  The study was a randomized, double-blind, placebo-controlled trial of clopidogrel administered following fistula creation in a large group of patients with advanced chronic kidney disease or ESRD. The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters; however, early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis. The FISTULA study aimed to investigate the ability of platelet inhibition to prevent early fistula failure and increase the number of fistulas that ultimately become usable for hemodialysis access.

Participants with chronic kidney disease or ESRD who underwent creation of a new native arteriovenous (AV) fistula were randomized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery.  The primary outcome was fistula thrombosis, determined by physical examination at 6 weeks. The secondary outcome was failure of the fistula to become suitable for dialysis. The study found that clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis.
DOI: 10.58020/hqfv-a985
title: Effect of Metabolic Control at Onset of Diabetes on Progression of Type 1 Diabetes

description: The purpose of this study is to find out if very tight blood glucose control from the onset of Type 1 Diabetes can preserve beta cell function. Study subjects will be randomly assigned to receive either standard diabetes management or intensive diabetes management, which involves several days of closed loop therapy followed by home use of a continuous glucose monitor and insulin pump.
DOI: 10.58020/mpam-ae97
title: Efficacy of Amitriptyline for the Treatment of Painful Bladder Syndrome (PBS) in Newly Diagnosed Patients

description: The Interstitial Cystitis Clinical Trials Group (ICCTG) RCT1 was a pilot clinical trial using a 2x2 factorial study design with double masked drug treatment to evaluate the feasibility of oral pentosan polysulfate (PPS) and oral hydroxyzine in patients with interstitial cystitis (IC).  IC is a bladder syndrome characterized as painful, debilitating and chronic, with no widely accepted effective treatment. Characteristic symptoms include pain with bladder filling, and marked urinary frequency (to relieve pain). The presentation of symptoms can be quite variable among patients, suggesting that IC is a multi-factorial syndrome with several proposed etiologies, some of which may be interrelated.
Subjects with IC were randomized over 18 months and followed for 24 weeks. The primary endpoint was a patient reported global response assessment (GRA) of overall symptoms. Secondary endpoints included symptom indexes and patient reports of urinary pain, urgency and frequency.  The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC.
DOI: 10.58020/s147-rh61
title: Evaluate the Efficacy of Intravesical Bacillus Calmette Guerin (BCG), for the Treatment of Interstitial Cystitis (IC)

description: The ICCTG RCT2 study was a randomized, placebo-controlled, two-arm clinical trial that investigated the efficacy and safety of intravesical Bacillus Calmette-Guerin (BCG) therapy in treating patients with treatment refractory Interstitial Cystitis (IC). IC is a bladder syndrome characterized as painful, debilitating and chronic, with no widely accepted effective treatment. Characteristic symptoms include pain with bladder filling, and marked urinary frequency (to relieve pain). The presentation of symptoms can be quite variable among patients, suggesting that IC is a multi-factorial syndrome with several proposed etiologies, some of which may be interrelated.

Subjects with IC were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34 recorded in a diary. Although the safety profile for BCG was acceptable, the therapy did not show significant benefit compared to placebo.
DOI: 10.58020/9kxb-yv28
title: Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction

description: Postcolecystectomy pain is a common clinical problem for the more than 70,000 patients who undergo this procedure annually.  Of those 70,000 patients, at least 10% report experiencing pain following the procedure.  Patients who have no significant abnormalities on imaging or laboratory testing often undergo endoscopic retrograde cholangiopancreatography (ERCP) in hopes of finding stones or other pathology.  The current practice of performing ERCP in these patients is not supported by evidence, causing several authors to express concerns about the procedure.  Patients who do not benefit from the procedure often undergo more ERCPs and surgical interventions.    

The EPISOD trial is a parallel, randomized, double-blinded, sham-controlled, multicenter Phase III clinical trial of endoscopic sphincterotomy as treatment for adults 18 to 65 years of age diagnosed with SOD III.
DOI: 10.58020/jdgh-kg90
title: Family Investigation of Nephropathy and Diabetes

description: The Family Investigation of Nephropathy and Diabetes (FIND) was a multicenter observational study designed to identify genetic determinants of diabetic kidney disease. Study subjects were recruited from eleven centers and in many ethnic groups throughout the United States for a genome-wide association study (GWAS). Two additional strategies were also used to localize susceptibility genes: a family-based linkage study and a case-control study using mapping by admixture linkage disequilibrium (MALD).
In the family-based study, participants with diabetic nephropathy were recruited with their parents and selected siblings. Linkage analyses were conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy and related quantitative traits.  Subsequently, a GWAS was carried out.

Two types of MALD studies were done. The first was a case-control study of unrelated individuals of Mexican American heritage in which both cases and controls had diabetes, but only the case had nephropathy. The second was a case-control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring were genotyped when available to provide haplotype data.
Through the family and MALD studies, the FIND study identified several genes that contribute to diabetic nephropathy, albuminuria, and glomerular filtration rate (GFR), including ApoL1.
DOI: 10.58020/180m-qa11
title: FibroScan in Pediatric Cholestatic Liver Disease

description: Non-invasive monitoring of liver fibrosis is an unmet and critical need within the clinical management of children with chronic liver disease. While liver biopsy is often used in the initial diagnostic evaluation of children with liver disease, subsequent surveillance liver biopsy is rarely performed in children because of its inherent invasiveness and risks. Therefore, our understanding of the natural history of fibrosis progression in children is limited. The patchy nature of fibrosis in many important pediatric liver diseases (e.g., biliary atresia (BA) and cystic fibrosis liver disease (CFLD)) limits the utility of sequential liver biopsy even if it were to be employed in clinical practice in pediatrics. Thus, non-invasive means of assessing liver fibrosis throughout the liver would be highly desirable and clinically useful in pediatric hepatology. The Childhood Liver Disease Research Network (ChiLDReN) is poised and uniquely qualified to conduct a comprehensive longitudinal assessment of the utility of FibroScan™-specific elastography, liver stiffness measurement (LSM) as a measure of hepatic fibrosis in children with serious chronic cholestatic liver disease.

The FibroScan in Pediatric Cholestatic Liver Disease (FORCE) study, a natural history study within ChiLDReN, was a cross-sectional and longitudinal assessment of the utility of LSM in children with chronic cholestatic liver disease. Study participants were from 13 ChiLDReN sites in the U.S. and Canada, and were also enrolled in the PROBE, BASIC, or LOGIC studies. FORCE participants were evaluated for a period of up to 24 months to assess the non-invasive ultrasound tool (FibroScan™) to detect and quantify global liver fibrosis in children with biliary atresia (BA), alpha-1 antitrypsin deficiency (A1ATD), and Alagille syndrome (ALGS). The participants were non-fasted and non-sedated during data collection. There were three visits in the study: baseline, 12-month follow-up, and 24-month follow-up. Clinical data and biosamples were collected at each visit along with repeated FibroScan measurements such as liver stiffness measurements (LSM) to quantify liver fibrosis, and controlled attenuation parameter (CAP) to quantify liver steatosis.

Baseline data are available from the Repository.
DOI: 10.58020/235v-4k70
title: FL3X: An Adaptive Intervention to Improve Outcomes for Youth With Type 1 Diabetes

description: The FL3X Adaptive Intervention was designed to increase adherence to T1D self-management including medical management (blood sugar testing and insulin dosing), diet, and physical activity. FL3X relies on MI, and problem-solving skills training (PSST) as the basis for the counseling strategy, and creates a coherent integration across three key components of 1) behavior family systems therapy focused on family communications and teamwork; 2) individualized diabetes education in response to knowledge gaps relevant to behavioral goal attainment; and 3) use of currently available communications technology to support behavioral goal attainment through participant-defined reminders and motivational boosters, and/or peer support.

All FL3X intervention participants received "FL3X-Basic", which was the initial 3-month intervention that includes 4 sessions (40-60 min), supplemented with short additional contacts (via text, email, or web-based communication) as needed. Thereafter, applying principles of adaptive interventions, based on a decision rule using A1c values measured at defined intervals, participants are iteratively assigned to "FL3X-Check-in" or "FL3X-Regular", both of which continue with MI and PSST for the underlying counseling strategy. In FL3X-Check-in, participants who are doing well ("responders") will receive minimal ongoing support to reinforce successful strategies through brief monthly "touch-base" contacts. In FL3X-Regular, those who are "Regular-responders" will have a minimum of 3-4 in-person full-length sessions (40-60 min) over each 6-month interval, with additional brief contacts as needed (e.g., text, voice, or internet). FL3X participants randomized to the control group received usual care.