The National Institute of Diabetes & Digestive & Kidney Diseases

The ALFSG is collecting biosamples and information on the natural history, causes and outcomes of Acute Liver Failure (ALF) in the United States. In addition to the database, a clinical trial was conducted to test whether the drug N-acetylcysteine improves outcome (survival) for patients with ALF not caused by acetaminophen overdose has recently been published. Results can be found at:http://www.ncbi.nlm.nih.gov/pubmed/19524577?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract
Additional information can be obtained at: www8.utsouthwestern.edu/utsw/cda/dept25203/files/89624.html

Adolescent Bariatrics: Assessing Health Benefits and Risks (Teen-LABS)

The Teen-LABS consortium is made up of five clinical centers and a data coordinating center. The goal of Teen-LABS is to facilitate coordinated clinical, epidemiological, and behavioral research in the field of adolescent bariatric surgery, through an observational study protocol for uniform data collection pre-operative, at surgery, and through 2 years post-operative at participating centers performing bariatric surgery on teenagers. The use of standardized definitions and data-collection instruments for sequential patients scheduled for surgery at each site will yield meaningful evidence-based recommendations for patient evaluation, selection, and follow-up care. In addition to investigating surgical outcomes, another broader goal of Teen-LABS is to better understand the etiology, pathophysiology, and behavioral aspects of severe obesity in youth and how this condition affects human beings over time. Additional information can be found at: www.cincinnatichildrens.org/research/project/teen-labs/

For more information, contact Dr. Mary Horlick, DDN, Director, Pediatric Clinical Obesity Program.

This study supports nine liver transplant centers with expertise in adult living-donor liver transplantation (LDLT) and a central data coordinating center. The major aims of A2ALL are as follows:

• Quantify the impact of choosing LDLT on the candidate for transplantation
• Characterize the difference between LDLT and deceased donor liver transplant (DDLT) in terms of post-transplant outcomes, including patient and graft survival, surgical morbidity, and resource utilization on the recipient of a transplant
• Determine the short- and long-term health and quality of life (QOL) impact of donation, including (a) morbidity after liver donation and (b) long-term health-related QOL of donors.
• Standardize and assess the role of "informed consent" in affecting the decision to donate and satisfaction after living liver donation
• Other aims include comparison of the severity of recurrence of hepatocellular carcinoma for DDLT versus LDLT, the systematic characterization of liver regeneration and function in donors and recipients, the evaluation of the differences in the immune response to LDLT versus DDLT, and the establishment of a robust data and sample repository on liver transplantation that may be used to study clinical and biological questions as new technologies and resources become available. Patients enrolled in the study will be followed and managed in a standardized fashion. Additional information can be obtained at: http://www.nih-a2all.org/
  

Childhood Liver Disease Research and Education Network (ChiLDREN)

The overall goal of ChiLDREN is to establish a database of clinical information and serum and tissue samples from children across the United States and Canada with Biliary Atresia, Idiopathic Neonatal Hepatitis, Cystic Fibrosis Liver Disease, Alagille Syndrome, Alpha-1 Antitrypsin Deficiency, Bile Acid Synthesis Defects, Mitochondrial Hepatopathies, and Progressive Familial Intrahepatic Cholestasis in order to facilitate research and to perform clinical, epidemiological, and therapeutic trials in these important pediatric liver diseases. Three NIDDK-funded consortia, Biliary Atresia Research Consortium (BARC), Cholestatic Liver Disease Consortium (CLiC), and the Cystic Fibrosis Liver Disease (CFLD) Network were consolidated to form ChiLDREN. Additional information can be obtained at:
http://www.childrennetwork.org

For more information, contact Dr. Averell Sherker, DDN, Senior Scientific Advisor, Viral Hepatitis and Liver Diseases.

Efficacy and Mechanisms of Glutamine Dipeptide in the Surgical Intensive Care Unit (GLND)

The GLND trial is a multi-center, double-blind, placebo-controlled, intent-to-treat Phase III trial, designed to determine the effect of parenteral glutamine (GLN) dipeptide on important clinical outcomes in patients requiring surgical intensive care unit (SICU) care and parenteral nutrition after cardiac, vascular, or intestinal surgery. Patients who required PN and SICU care will receive either standard glutamine (GLN)-free PN (STD-PN) or isocaloric, isonitrogenous alanyl-glutamine dipeptide (AG)-PN until enteral feedings are established. The study will determine whether AG-PN decreases hospital mortality, nosocomial infection and other important indices of morbidity and will obtain mechanistically relevant observational data in the subjects on whether AG-PN a) increases serial blood concentrations of glutathione (GSH), heat shock proteins (HSP)-70 and -27, and glutamine; b) decreases the serum presence of the bacterial products flagellin and lipopolysaccharide (LPS) and the adaptive immune response to these mediators; and c) improves key indices of innate and adaptive immunity. Additional information can be obtained at: http://www.sph.emory.edu/GLND

For more information, contact Dr. Mary Evans, DDN, Director, Special Projects in Nutrition, Obesity, and Digestive Diseases.

An observational study examining the risk factors associated with the long-term complications of type 1 diabetes. The study began in 1994 and follows the 1441 participants previously enrolled in the Diabetes Control and Complications Trial (DCCT).

For more information, contact Dr. Catherine Cowie, DEM, Director, Diabetes Epidemiology Program.

Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD)

The EPISOD study is a prospective, double-blind, randomized, sham-controlled, multi-center clinical trial. The EPISOD study enrolls subjects who have received a prior cholecystectomy and are diagnosed with the clinical syndrome of Sphincter of Oddi Dysfunction III (SOD III) as defined by the Rome III criteria. The goal of the EPISOD study is to asses the value of endoscopic sphincterotomy as a treatment for adult subjects categorized as SOD III suffering from pain after cholecystectomy and to define the role of manometry in treating these patients. Additional information can be obtained at: www.episod.org

For more information, contact Dr. Averell Sherker, DDN, Senior Scientific Advisor, Viral Hepatitis and Liver Diseases.

Gastroparesis Clinical Research Consortium (GpCRC)

The GpCRC is focusing on the etiology, natural history, and therapy of gastroparesis. The goal of this consortium is to perform clinical, epidemiological, and therapeutic research in gastroparesis and provide an infrastructure that can rapidly and efficiently design and conduct clinical trials for effective medical, surgical, or other interventions to improve treatment of patients with gastroparesis. The GpCRC studies comprise well characterized individuals with diabetic, surgical, and idiopathic gastroparesis. Additional information can be obtained at: www.jhucct.com/gpcrc

For more information, contact Dr. Frank Hamilton, DDN, Director, Gastrointestinal Motility Program.

Hepatitis B Research Network (HBRN)

The Hepatitis B Research Network (HBRN) brings together clinical centers with expertise in caring for patients with chronic hepatitis B virus (HBV) infection. An estimated 2 billion people worldwide have been infected with HBV and about 400 million persons are living with chronic HBV infection. Of those with childhood-acquired chronic HBV infection, it is estimated that 25% will later succumb to liver-related complications of cancer and cirrhosis if left untreated. The prevalence of HBV infection is uneven throughout the world, with significant burdens in Asia and the Pacific Islands, sub-Saharan Africa, the Amazon Basin, and Eastern Europe. The goal of the Network is to conduct research on chronic hepatitis B, in order to better understand the physiological effects of the disease and develop effective treatment strategies with the currently available therapies. Additional information can be obtained at: www.hepbnet.org

This prospective, randomized, controlled clinical trial studied long-term therapy with peginterferon in patients with chronic hepatitis C. Patient enrollment began in 2000 and was completed in 2003 at 10 clinical centers, which were supported by a data coordinating center, virological testing center, and central sample repository. Patients with chronic hepatitis C and advanced fibrosis or cirrhosis on liver biopsy who failed to respond to a previous course of interferon alfa were enrolled in this study. Patients were initially treated with a 24-week course of peginterferon alfa-2a and ribavirin. Patients who remained hepatitis C virus RNA positive were then randomized to receive maintenance, low-dose peginterferon or to be followed on no treatment. Liver biopsies were done before enrollment and after 2 and 4 years of treatment or follow-up. The endpoints were development of cirrhosis, hepatic decompensation, hepatocellular carcinoma, death, or liver transplantation. 1050 patients were randomized and followed through the 4 year randomized phase of the trial and as long as 4 years off treatment. Serum samples collected at multiple time points, DNA and liver tissue are available for scientific investigation. Additional information can be obtained at: www.haltctrial.org

High-dose Ursodiol Therapy of Primary Sclerosing Cholangitis (HUSC)

HUSC is a multi-center placebo-controlled trial of ursodiol in primary sclerosing cholangitis (PSC). A total of 150 patients with previously untreated PSC without cirrhosis were randomly assigned to receive high doses of ursodiol (20-25 mg/kg/day) or placebo for two years. Patients underwent medical evaluation, endoscopic retrograde cholangiography, and liver biopsy before randomization and again at two-year intervals. The endpoints of therapy were progression of hepatic fibrosis, liver decompensation, liver transplantation, or death. The treatment phase of the study was stopped for futility in June 2008; however, patients continue to be followed. Ongoing mechanistic studies are underway. Results from this study can be obtained at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758780/?tool=pubmed

Irritable Bowel Syndrome Outcome Study (IBSOS)

This multi-center clinical trial is designed to assess the short-term and long-term efficacy of cognitive behavior therapy (CBT) for irritable bowel syndrome (IBS) using two treatment delivery systems: self administered CBT and therapist administered CBT. Long term project goals are to develop an effective self-administered behavioral treatment program that can enhance the quality of patient care, improve clinical outcomes, and decrease the economic and personal costs of one of the most prevalent and intractable gastrointestinal disorders.

For more information, contact Dr. Frank Hamilton, DDN, Director, Gastrointestinal Motility Program, Gastrointestinal Mucosa and Immunology Program, and Gastrointestinal and Nutrition AIDS Program.

Longitudinal Assessment of Bariatric Surgery (LABS) Consortium

The LABS consortium comprises six clinical centers and a data coordinating center. The goal of LABS is to facilitate coordinated clinical, epidemiological, and behavioral research in the field of bariatric surgery, through the cooperative development of common clinical protocols and a bariatric surgery database that will collect information from participating clinical centers. LABS will help pool the necessary clinical expertise and administrative resources to facilitate the conduct of multiple clinical studies in a timely, efficient manner. Also, the use of standardized definitions, clinical protocols, and data-collection instruments will enhance the investigator's ability to provide meaningful evidence-based recommendations for patient evaluation, selection, and follow-up care. The consortium was funded in September 2003. The investigators have collaboratively developed a core database and clinical protocols, and subject enrollment began in early 2005. Additional information can be obtained at: www.niddklabs.org

For more information, contact Dr. Mary Evans, DDN, Director, Special Projects in Nutrition, Obesity, and Digestive Diseases.

Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

The NASH CRN researches the nature and underlying cause of NASH and conducts clinical studies on prevention and treatment. Approximately 1,500 pediatric and adult participants throughout the United States and Canada with nonalcoholic fatty liver disease (NAFLD) have enrolled into a database which began in late 2003. The NASH CRN has recently reopened the database to enroll additional pediatric and adult participants with NAFLD. Serum, liver tissue, and genomic DNA samples are being collected and stored in the NIDDK repository for ongoing as well as future studies. A three-arm randomized, placebo-controlled clinical trial of pioglitazone versus vitamin E completed enrollment in 2009. In addition to this adult trial, a similar trial in pediatric NASH patients randomized 180 children to receive treatment with vitamin E, metformin, or placebo. Additional information can be obtained at: www.nashcrn.com

Pediatric Acute Liver Failure (PALF) Study

This multi-center, multi-national collaborative group of pediatric clinical liver centers is aimed at identifying, characterizing, and developing management strategies for infants, children, and adolescents who present with acute liver failure (ALF). In addition to a database of pediatric patients with ALF, a clinical trial is being conducted to test whether the drug N-acetylcysteine (NAC) improves outcome (survival) for patients with ALF not caused by acetaminophen overdose. Additional information can be obtained at: www.palfstudy.org

For more information, contact Dr. Averell Sherker, DDN, Senior Scientific Advisor, Viral Hepatitis and Liver Diseases.

Peginterferon and Ribavirin for Pediatric Patients with Chronic Hepatitis C (Peds-C)

This prospective, randomized controlled trial was completed in 2008 and studied peginterferon therapy, with or without ribavirin, in children with chronic hepatitis C. Approximately 120 children were randomly assigned to receive peginterferon alfa-2a alone or peginterferon with ribavirin for 48 weeks. Samples of blood, genomic DNA, and liver tissue are stored in the NIDDK repositories. A long-term follow up study of the clinical trial participants is underway. Additional information can be obtained at: www.pedsc.org

Study of Nutrition in Acute Pancreatitis (SNAP)

SNAP is a randomized multi-center clinical trial designed to test whether duodenojejunal (DJ) feeding is more effective than nasogastric (NG) feeding in providing enteral nutrition to patients with severe acute pancreatitis. SNAP will enroll participants with severe acute pancreatitis admitted to the intensive care unit at eight clinical centers. Upon enrollment, participants are assigned to NG or DJ feeding and managed for up to 28 days or until weaned on to solid food. Follow-up continues until participants are discharged from the hospital or for a maximum of 60 days. Outcomes relate to feeding tolerance and failure, nutritional status, risk for life-threatening pancreatic/systemic complications, and hospital mortality. Additional information can be found at: www.snaptrial.org

The network is a group of collaborating investigators who conduct long-term studies and clinical trials of the most commonly used surgical, pharmacological, and behavioral approaches for management of urinary incontinence in women diagnosed with stress and mixed incontinence.