PCB stands for the Partners Calciphylaxis Biobank. Calciphylaxis, a vascular calcification disorder, is a rare and serious disorder characterized by calcification of dermal arterioles. There are significant gaps in the understanding of the pathophysiology and risk factors for calciphylaxis. At present, there is no effective treatment. Uncertain pathobiology, rare incidence and lack of collaborative approach have been some of the major limiting factors towards treating calciphylaxis. The Partners Calciphylaxis Biorepository (PCB) aims to address these gaps within calciphylaxis research by utilizing existing and, when necessary, developing new infrastructure to support the consent of patients and the collection of dedicated samples for a calciphylaxis repository. ClinicalTrials.gov/NCT03032835
VitK-CUA stands for Evaluation of Vitamin K Supplementation for Calcific Uremic Arteriolopathy. Calcific uremic arteriolopathy a.k.a. calciphylaxis is a vascular calcification disorder seen in dialysis patients. Calcific uremic arteriolopathy has 60-80% one-year mortality and significant morbidity associated with non-healing and extremely painful skin lesions. At present, there is no effective treatment for calcific uremic arteriolopathy. Vitamin K is an important vitamin for inhibiting vascular calcification. It is known to increase the circulating levels of carboxylated Matrix Gla Protein, a potent inhibitor of vascular calcification. However, the effects of vitamin K supplementation in patients with calcific uremic arteriolopathy are unknown. The purpose of this study is to conduct a pilot randomized controlled trial to examine the effects of oral vitamin K supplementation on circulating levels of anti-calcification factor (carboxylated Matrix Gla Protein) and clinical outcomes in patients with calcific uremic arteriolopathy. Clinicaltrials.gov/NCT02278692
CarRAAT stands for CARbamylation in Renal Disease-modulation With Amino Acid Therapy. This is a pilot study to evaluate the effects of amino acid supplementation on the structure of certain proteins in the blood of dialysis patients. Patients with end stage renal disease (ESRD) usually have high levels of urea that may interact with blood proteins and change their structure by a process known as carbamylation. We are interested in investigating whether carbamylation is linked to adverse outcomes in dialysis patients and have hypothesized that supplementation with a balanced formulation of amino acids can reduce the amount of carbamylation that occurs. In this study we will evaluate the direct effects of amino acid therapy on protein carbamylation in a small group of dialysis patients. We are actively recruiting subjects for this study. ClinicalTrials.gov/NCT01612429
The NGAL Test is a study sponsored by BioPorto Diagnostics A/S in Denmark to determine the association of urine and plasma levels of NGAL (neutrophil gelatinase-associated lipocalin) with the clinical diagnosis of acute kidney injury (AKI) in intensive care patients. Secondary objectives of the study are 1) To determine any trends in NGAL values relating to gender, age, race or ethnicity; 2) To determine the association of the ratio of the urine and plasma levels of NGAL with the clinical diagnosis of AKI; 3) To determine the association of heparin plasma levels of NGAL with the clinical diagnosis of AKI; 4) To establish a biorepository of the leftover specimens to be used for further investigation.
CALISTA is a Phase 3, multi-center, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Thiosulfate Injection for treatment of acute calciphylaxis-associated pain in chronic hemodialysis patients. Acute calciphylaxis- associated pain intensity will be the primary outcome measure. We are actively recruiting subjects for this study. ClinicalTrials.gov/NCT03150420
PROMETHEUS stands for PRedictive BiOlogical Markers for The HEpatorenal Syndrome. It is challenging to differentiate hepatorenal syndrome (HRS) from other etiologies of renal failure in patients with liver disease. Therefore, HRS is usually diagnosed after several days once other renal failure etiologies have been excluded. PROMETHEUS is a prospective study enrolling patients with decompensated liver failure and acute kidney injury (AKI) at the MGH that aims to identify biological markers useful in the early diagnosis, prediction, and prognosis of hepatorenal syndrome (HRS). We are enrolling healthy subjects and subjects with sepsis to better understand the biology and natural history of the biomarkers. Dr. Ananth Karumanchi from BIDMC is a key collaborator for this study.
EMD Serono Lupus Study is a characterization of pathogenic factors and cells in the blood and urine from patients with Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN). The primary purpose is to prospectively collect and store bio-specimens (blood and urine) and clinical data on patients with SLE, with LN, and healthy controls. The goal is that through these studies, we will validate lead drug candidates, identify novel biomarkers and discover novel targets and/or pathways to treat SLE and LN.
AWAKIN stands for Assessment of Women after Acute Kidney INjury. The goal of this study is to assess for subclinical renal and vascular disease following acute kidney injury (AKI) in young women. AKI is a risk factor for future cardiovascular disease and chronic kidney disease. We have recently described that an episode of AKI results in higher rates of preeclampsia in subsequent pregnancies. AKI has not been studied in young women even though the consequences of AKI may be more immediate. AWAKIN is enrolling women with a history of AKI and healthy controls to undergo provocative physiologic renal and vascular testing in the MGH Clinical Research Center. Our goal is to identify pathways that are altered after AKI that can be targeted to prevent future disease. AWAKIN will begin enrollment in Spring 2017.
STORK stands for STudy Of Regulation of Kidney Function in Pregnancy. During normal pregnancy, there are profound changes in renal circulation including a 50% rise in glomerular filtration rate (GFR) by mid-gestation. Outside of pregnancy, GFR is known to vary with changes in physiological demands. The difference between an individual’s maximal and baseline GFR has been termed renal functional reserve (RFR). In this study we will use a novel method to quantify RFR in pregnancy and determine if differences in RFR affect late pregnancy outcomes like preeclampsia. STORK will begin enrollment in Spring/Summer 2017.
KINDRED stands for Kidney Information Network for Disease Research and Education. The demands for highly characterized human samples have grown in recent years, given the adoption of advanced techniques in genotyping and sequencing. Traditional methods of consenting patients and collecting samples are time-consuming and costly. There is a movement to develop methods to remotely consent subjects and collect samples, allowing for more efficiency and broader outreach efforts. However, comparable efforts in studies focused on diagnosing patients with rare diseases are absent. The KINDRED study intends to address these needs by creating a new infrastructure to support the consent of ESRD patients nationally, with the collection of dedicated samples for a tissue repository. This tissue repository will allow for genetic screening of a geographically diverse population, assist in identification of rare diseases in ESRD, such as Fabry, and collect research-quality information on risk factors and outcomes from an ethnically heterogeneous population of dialysis patients. KINDRED is a prospective, observational cohort study that will enroll up to 10,100 hemodialysis patients throughout the Unites States with and without known diagnosis of Fabry disease, but at risk for Fabry disease (e.g. end-stage renal disease of unknown etiology, younger male, initiating dialysis without a kidney biopsy, etc.) The plan for screening ~10,000 younger men is to recruit those without a known diagnosis so as to capture the frequency of undiagnosed/missed Fabry disease on dialysis in the US today. We will test patients for alpha galactosidase A enzyme activity using a dried blood spot test. If the blood spot test reveals low enzyme activity, we will then confirm using DNA analysis, which will have already been collected in all subjects. We also expect to enroll between 50-100 patients with a known diagnosis of Fabry disease utilizing our internet recruitment strategies to investigate genotype-phenotype correlations across renal, cardiac, cerebrovascular, and other clinical endpoints. Investigator Sponsored Study Funding: Sanofi Genzyme.
ARMORR stands for AcceleRated MOrtality in Renal Replacement. The United States Renal Data System (USRDS) is the largest epidemiological database of patients with end-stage renal disease (ESRD) throughout the US, and studies utilizing the USRDS and similar studies emanating from large dialysis providers have served as the benchmark for guiding the care of all dialysis patients in the US. While these databases have been an excellent resource for testing hypotheses, lack of concomitant blood samples has prevented a large-scale testing of hypotheses necessitating biological samples. To overcome this limitation, we established a USRDS-like clinical study with the largest US dialysis provider to prospectively acquire research quality demographic data and concomitant biological samples. ArMoRR is a prospective cohort study of incident hemodialysis patients living throughout the US (>1000 centers) with detailed demographic data updated daily, and research quality blood samples collected every 3 months from the initiation of chronic hemodialysis (HD). This study is closed to enrollment. ClinicalTrials.gov/NCT00505180
LUCID stands for Longitudinal US/Canada Incident Dialysis study. It is a large prospective multi-center observational study involving patients initiating chronic dialysis in the United States and Canada. This study collects research-quality information on risk factors and outcomes and stores biological specimens at baseline and in long-term follow-up. These stored specimens are a unique aspect of the study. Such specimens permit measurements of currently available biochemical markers, proteomic and genetic parameters (proteins and DNA) that are not measured as part of routine care. In addition, LUCID has a sub-study incorporated in its study design that tests independent relationships between biochemical and genetic markers and coronary artery calcification and left ventricular hypertrophy in the incident dialysis population. We are actively recruiting subjects for this study. ClinicalTrials.gov/NCT01427374
MACS stands for Metabolic Abnormalities in College Students. MACS is a study of healthy college-aged individuals with metabolic profiling done in collaboration with the Broad Institute. Subjects were admitted to the MIT CRC for detailed physiologic measurements including oral glucose tolerance testing and blood pressure monitoring. We are currently conducting a substudy on vitamin D metabolism. This study is closed to enrollment.
MOMS stands for MGH Obstetrical Maternal Study. MOMS is a large prospective cohort study of pregnant women which enrolled subjects between 1998 and 2006. We collected blood samples and clinical information on women receiving prenatal care at MGH and affiliated health centers. Although enrollment for the study has ended, we are conducting ongoing case-control and prospective cohort studies using the MOMS database and sample bank. We are interested in discovering bio markers which can be used to develop screening and diagnostic tests for preeclampsia, gestational diabetes, intrauterine growth restriction, and other related disorders. We frequently collaborate with the laboratory of S. Ananth Karumanchi at the Beth Israel Deaconess Medical Center in this work. In addition, we are interested in determining how complications during pregnancy predict the risk of future morbidity and mortality. This study is closed to enrollment.
DIVINE stands for Dialysis Infection and VItamin D In New England. It focuses on vitamin D and the immune system in humans, particularly in the setting of renal disease. DIVINE is a randomized placebo control trial of ergocalciferol in patients with end stage renal disease aimed at identifying the effects of 25-hydroxyvitamin D on various aspects of the inflammatory cascade as well as clinical outcomes. Translational studies on the effect of 25-hydroxyvitamin D on the activity of immune cells are being undertaken in collaboration with the lab of H. Shaw Warren, MD. This study is closed to enrollment. ClinicalTrials.gov/NCT00892099
PRIMO stands for Paricalcitol capsules benefits in Renal failure Induced cardiac MOrbidity (PRIMO) trial in CKD. It is an international multi-center randomized control trial of paricalcitol (active Vitamin D analog) in patients with chronic kidney disease. Its aim is to investigate the effects of paricalcitol capsules on changes in cardiac structure and function in subjects with Stage 3/4 Chronic Kidney Disease who have left ventricular hypertrophy. All subjects have been enrolled and are now being followed for primary and secondary outcomes. ClinicalTrials.gov/NCT00497146
VITAL-Echo Impact of VItamin D Supplementation on Cardiac Structure and Function. The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in 20,000 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or fish oil (1 gram of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study (VITAL-Echo) is being conducted among participants in VITAL and will examine whether vitamin D compared to placebo: (1) reduces left ventricular (LV) mass in elderly individuals as measured with 2-dimensional echocardiography and (2) improves LV systolic and diastolic function as measured with tissue Doppler echocardiography. As Co-Principal Investigators, Dr. Ravi Thadhani and Dr. Thomas Wang lead this effort. ClinicalTrials.gov/NCT01630213