NUDACC Collaborations

This randomized, double blind, placebo controlled clinical trial will evaluate the effectiveness of 81 mg v. 162 mg of aspirin for preventing hypertensive disorders of pregnancy in over 10,000 pregnant individuals who meet USPSTF criteria for aspirin therapy. The trial is formally powered to evaluate heterogeneity of treatment effects among subgroups defined by self-reported maternal race, obesity, age, social vulnerability index, gestational age at aspirin initiation, and other risk factors.

• Study Leaders: Maged Costantine, MD; Kara Rood, MD
• NUDACC Leaders: Denise Scholtens, PhD; Abigail R. Smith, PhD; Nathan Gill, PhD
• Planned Enrollment: 10,742
• Number of Sites: 11

MCD, FSGS, MN, and IgAN are rare glomerular diseases of the kidney that cause serious illness including kidney failure and high mortality, generating enormous individual and societal burden. CureGN has assembled nephrologists, researchers with expertise in different scientific disciplines, and patients in a consortium that maintains and analyzes a large, longitudinal observational dataset and biosamples like blood, urine and images of kidney biopsies. This initiative has developed a critical infrastructure that will advance our ability to study, classify, characterize, diagnose, and treat primary glomerular diseases of the kidney.

• Website: https://www.curegn.org/
• Study Leaders: Laura H. Mariani, MD, MSCE; Abigail R. Smith, PhD; Crystal A. Gadegbeku, MD
• NUDACC Leaders: Abigail R. Smith, PhD; Margaret M. Banker, PhD
• Planned Enrollment: 3,000 participants
• Number of Sites: 71
• Publications
  • CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease
  • Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes
  • Age of Onset and Disease Course in Biopsy-Proven Minimal Change Disease: An Analysis From the Cure Glomerulonephropathy Network
  • CureGN Consortium (2023). Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
  • Increased risk of kidney failure in patients with genetic kidney disorders
  • Proteinuria Trajectory and Disease Progression in Children and Adults with IgA Nephropathy/Vasculitis
  • Risk Factors for Disease Progression for Adults and Children With Membranous Nephropathy in the Cure Glomerulonephropathy Network (CureGN)
  • Full publication list here
• Media Coverage
  • Study Uncovers Glomerular Disease Outcomes Across the Lifespan
  • ​​NEPTUNE and CureGN Driving Precision Nephrology Forward, With Alessia Fornoni, MD, PhD

The Dementia Risk Prediction Project (DRPP) is a consortium of 11 cohorts spanning multiple sites across the US and Europe. This project provides harmonized data for all contributing cohorts and is focused on development and validation of dementia risk prediction tools.

• Website: https://drpp.northwestern.edu/
• Study Leaders: Norinna Allen, PhD
• NUDACC Leaders: Denise Scholtens, PhD
• Planned Enrollment: Analyses of large-scale multicenter extant data from over 53,000 participants
• Number of Sites: 14
• Publications:
  • Cohort Profile: Dementia Risk Prediction Project (DRPP)
  • psHarmonize: Facilitating reproducible large-scale pre-statistical data harmonization and documentation in R

This is a multi-site feasibility trial of an embedded emergency department (ED) physical therapy care model for low back pain at two EDs in the Northwestern Medicine and University of Utah Health systems. The study intervention (embedded ED physical therapy) is a reconceptualization of the traditional outpatient physical therapy care model in which we place a physical therapist directly in the ED to initiate timely care for patients with low back pain; we previously evaluated this intervention in a single center randomized trial.  This multi-site feasibility trial will be comprised of 9 months of active intervention and 12 months of longitudinal data collection. The two sites will be parallel randomized 1:1 to receive either the embedded ED physical therapy condition (intervention, n=1) or usual care (control, n=1) via simple randomization. This trial focuses on feasibility outcomes – such as our ability to enroll participants, deliver the intervention with fidelity, and collect longitudinal patient-reported outcome data and electronic health record data – but a future multi-site full-scale trial will focus on the outcomes of pain-interference and opioid use.

• Study Leaders: Howard S. Kim, MD, MS, Margaret M. Banker, PhD, Scott T. Youngquist, MD, MS
• NUDACC Leaders: Margaret M. Banker, PhD
• Planned Enrollment: 1650 participants
• Number of sites: 2

FIT-BRAIN is a phase 2/3, randomized, double-blind, placebo-controlled multicenter clinical trial to evaluate the efficacy of fresh frozen plasma injection in improving outcomes in subjects with moderate to severe traumatic brain injury

• Study Leaders: Hasan Alam, MD
• NUDACC Leaders: Nathan Gill, PhD; Denise Scholtens, PhD
• Planned Enrollment: 357 participants
• Number of Sites: 8

This multicenter observational study is designed to characterize the glycemic profile of pregnancy to understand potential early indicators of dysglycemia during pregnancy and long-term sequelae. Continuous glucose monitoring technology will be central for data collection. NUDACC is the Biostatistics Research Center for this new, NIDDK-supported consortium, serving as a central leadership hub for all project coordination and data related components of the study.

• Website: www.gomomsstudy.org
• ClinicalTrials.gov: NCT04860336
• Study Leaders: William Lowe, MD; Uma Reddy, MD, MPH
• NUDACC Leaders: Denise Scholtens, PhD; Margaret Banker, PhD
• Planned Enrollment: 2150 participants
• Number of sites: 7
• Publications
  • Design, rationale and protocol for Glycemic Observation and Metabolic Outcomes in Mothers and Offspring (GO MOMs): an observational cohort study
  • Imputation of Missing Continuous Glucose Monitor Data

The goal of the ancillary study Glycemic Observation Using A1C for Gestational Diabetes Diagnosis (GO A1C GDM) is to improve hemoglobin A1C (A1C)’s ability to detect hyperglycemia in pregnancy and predict associated complications by adjusting for gestational changes in red blood cell (RBC) kinetics. GO A1C GDM will use ongoing multicenter GO MOMs study measurements from continuous glucose monitoring (CGM), hemoglobin A1C, and complete blood counts (CBCs), while adding additional hematologic measurements (single cell hemoglobin and volume measurements from CBCs, reticulocyte counts, and ferritin) at each time point to make these personalized RBC adjustments. To achieve this, GO A1C GDM will use mechanistic modeling of GO MOMs data to improve A1C-based glycemia estimation for the purpose of predicting hyperglycemia-associated adverse pregnancy outcomes.

• Study Leaders: Camille Powe, MD; John Higgins, MD
• NUDACC Leaders: Adin-Cristian Andrei, PhD
• Planned Enrollment: 2150 participants
• Number of Sites: 7

The GROWTH Study, Glycemia Range and Offspring Weight and adiposity in response To Human milk, aims to understand how human milk (HM) susceptibility to maternal metabolism impacts offspring metabolism, identifying interventions to mitigate adverse developmental programming and to determine the impact of maternal glycemia in pregnancy on HM composition and effects of HM nutrients on offspring adiposity. Translational science approaches will determine how maternal glycemia alters mammary gland epithelial cell gene expression and how HM lipids across the range of maternal glycemia regulate infant adipoctyes. Capitalizing on the detailed metabolic phenotyping of the GO MOMs cohort, prospective HM profiling at 1, 2 and 6 months post-partum will be conducted in a cohort of 450 women to associate maternal glycemia during and after pregnancy, focusing on HM lipids known to regulate offspring adiposity (Aim 1). Mammary epithelial cells shed in expressed HM will be evaluated using transcriptomics (SubAim 1). For reproducibility, HM lipids will be compared to a separate validation cohort enrolling women with GDM. Offspring body composition will be measured to discern adiposity at months 1, 2, and 6 and 2 years, accounting for childhood diet (Aim 2). A human infant preadipocyte strain will be exposed to HM lipids collected and grouped by quartiles of maternal glycemia to determine mechanisms altering infant adipocyte development (Aim 3).

• Study Leaders: Jamie Josefson, MD, MS; Daniel Robinson, MD, MSc; Brigid Gregg, MD
• NUDACC Leaders: Adin-Cristian Andrei, PhD
• Planned Enrollment: 450 mother-infant dyads
• Number of Sites: 5

This observational cohort study will enroll 1,000 HAPO Follow-up study (FUS) offspring from 4 of the original HAPO centers. The study will encompass a comprehensive investigation of the cardiometabolic in utero environment and its association with cardiovascular health and arterial injury in young-adult offspring.

• Study Leaders: Wendy Brickman, MD; Donald Lloyd-Jones, MD, ScM
• NUDACC Leaders: Denise Scholtens, PhD; Lauren Balmert Bonner, PhD
• Planned Enrollment: 1,000 participants
• Number of Sites: 4

The overarching goal of the HeartShare program is to characterize mechanisms of disease and identify therapeutic targets in patients with heart failure with preserved ejection fraction via large-scale analyses of phenotypic data, images, and omics. 

• Website: www.heartsharestudy.org
• ClinicalTrials.gov: NCT05873634
• Study Leaders: Sanjiv Shah, MD; Abel Kho, MD; Yuan Luo, PhD; Denise Scholtens, PhD
• NUDACC Leaders: Denise Scholtens, PhD; Lauren Balmert Bonner, PhD
• Planned Enrollment: 10,000 low-touch registry; 1,000 deep-phenotyping participants
• Number of Sites: 6

This multicenter clinical trial is designed to confirm the treatment benefits of hyperbaric oxygen therapy for ulcerative colitis. The study will enroll participants with ulcerative colitis, hospitalized for an acute moderate to severe flare, from clinical sites across the Unites States. NUDACC is the Data Coordinating Center for this new, NIDDK-funded clinical trial.

• ClinicalTrials.gov: NCT05987852
• Study Leaders: Parambir Dulai, MD; Lauren Balmert Bonner, PhD
• NUDACC Leaders: Lauren Balmert Bonner, PhD
• Planned Enrollment: 126 participants
• Number of Sites: 17
• Publications: Clinical Trial Design Considerations for Hospitalised Patients With Ulcerative Colitis Flares and Application to Study Hyperbaric Oxygen Therapy in the NIDDK HBOT-UC Consortium

• Website: https://www.lcnstudy.org/
  
• ClinicalTrials.gov: NCT05740358
• Study Leaders: Jasmohan Bajaj, MD; Robert Brown, MD, MPH
• NUDACC Leaders: Abigail R. Smith; Daniela Ladner, MD, MPH
• Planned Enrollment: 1,200 participants
• Number of Sites: 13
• Publications: The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints

• ClinicalTrials.gov: NCT05832229
• Study Leaders: Elizabeth C. Verna, MD; Norah Terrault, MD, MPH
• NUDACC Leaders: Abigail R. Smith; Daniela Ladner, MD, MPH; Lauren Balmert Bonner, PhD
• Planned Enrollment: 204 participants
• Number of Sites: 12

Northwestern Embedded Emergency Department Physical Therapy Protocol for Acute Low Back Pain (NEED-PT) is a single center physician-randomized trial comparing a physical therapy intervention (pairing a physical therapist with an Emergency Department physician) vs. usual care in patients reporting to the Emergency Department with low back pain.

• ClinicalTrials.gov: NCT04921449
  
• Study Leaders: Howard Kim, MD, MS
• NUDACC Leaders: Jacob M. Schauer, PhD
• Planned Enrollment: 360 participants
• Number of sites: 1 (43 physicians across the Northwestern Emergency Department)
• Publications:
  • Embedded emergency department physical therapy versus usual care for acute low back pain: a protocol for the NEED-PT randomised trial
  • Cluster-Randomized Trials in Emergency Care Research

PREMEDIA is a multisite randomized noninferiority trial comparing a standard peroral endoscopic myotomy (POEM) to a personalized approach to POEM guided by clinical phenotypes and intraoperative physiologic measurement among patients with type I or II achalasia.

• Study Leaders: John Pandolfino, MD, Badih Joseph Elmnuzer, MD, MSc; Michael F. Vaezi, PhD, MD, MS; Jacob M. Schauer, PhD
• NUDACC Leaders: Jacob M. Schauer, PhD; Denise M. Scholtens, PhD
• Planned Enrollment: 370 participants for the noninferiority trial; 320 participants for the cohort study
• Number of Sites: 17
• ClinicalTrials.gov: NCT07293650
• Media: NIH Awards $12 Million to Northwestern Medicine for Precision Medicine in Achalasia

The DASH Study was part of the Rapid Acceleration of Diagnostics (RADx) initiative sponsored by the NIH, and was designed to evaluate the validity and accuracy of a point-of-care PCR test for the diagnosis of SARS-CoV-2 infection in symptomatic and asymptomatic individuals.

• Study Leaders: Chad Achenbach, MD, MPH
• NUDACC Leaders: Lauren Balmert Bonner, PhD
• Enrollment: 315 participants
• Number of Sites: 4
• Publications: Clinical Evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): a point-of-care PCR test for rapid detection of SARS-CoV-2 infection
• Media: Rapid PCR test receives FDA emergency use authorization

The GO MOMs Nutrition Study is an observational substudy nested within the GO MOMs parent study. Participants will complete 6 dietary recalls via the Automated Self-Administered 24-hour (ASA24) Dietary Assessment Tool during their pregnancies. The goal is to evaluate associations between dietary carbohydrate content at <22 weeks’ gestation and maternal glycemia 24-28 weeks’ gestation and neonatal birthweight.

• Study Leaders: Camille Powe, MD; Erin LeBlanc, MD, MPH
• NUDACC Leaders: Adin-Cristian Andrei, PhD
• Planned Enrollment: 840 participants
• Number of Sites: 7

The observational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study was designed to investigate associations of maternal glycemia during pregnancy with maternal glucose metabolism and child adiposity 11-14 years after delivery. HAPO Follow-Up involved oral glucose tolerance tests and physical exams in over 4800 mother-offspring pairs at 10 international study sites.

• Study Leaders: Boyd Metzger, MD; William Lowe, MD; Alan Dyer, PhD; Lynn Lowe, PhD
• NUDACC Leaders: Denise Scholtens, PhD
• Enrollment: 4,500 mother/offspring pairs
• Number of Sites: 10 international field centers
• Publications:
  • Primary findings published in JAMA: Association of Gestational Diabetes With Maternal Disorders of Glucose Metabolism and Childhood Adiposity
  • Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism
  • Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study
  • Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism
  • The Joint Associations of Maternal BMI and Glycemia with Childhood Adiposity

The Healthy Hearts for Michigan project aims to intervene in primary care clinics in Michigan via practice facilitation to help promote overall cardiovascular health for their patients; areas of focus are blood pressure control for patients with hypertension and smoking cessation for patients who are currently smoking.

• Website: https://www.healthyheartsformichigan.org/
• Study Leaders: Theresa Walunas, PhD; Anya Day, MPH
• NUDACC Leaders: Amy Krefman, MS; Jody Ciolino, PhD
  
• Actual Enrollment: 50 practices
• Publications:
  • Rationale and design for Healthy Hearts for Michigan (HH4M): A pragmatic single-arm hybrid effectiveness-implementation study
  • An Approach to Evaluating Multisector Partnerships to Support Evidence-Based Quality Improvement in Primary Care

This NIH/NIA-funded clinical trial was designed to investigate HIW in frail, older adults and involves 14 study sites.

• ClinicalTrials.gov: NCT03654807
• Study Leaders: Margaret Danilovich, PT, DPT, PhD
• NUDACC Leaders: Lauren Balmert Bonner, PhD
• Enrollment: 165 participants
• Number of Sites: 14 retirement communities

This Type II hybrid stepped wedge study is designed to evaluate effectiveness and implementation of patient-centered symptom management information for individuals with cancer. The study involves all Northwestern-affiliated regional centers. Implementation outcomes are evaluated across the health system; effectiveness patient-report outcomes will be evaluated on a subset of individuals who are randomized to usual or enhanced care symptom management systems.

• ClinicalTrials.gov: NCT03988543
• Study Leaders: Dave Cella, PhD
• NUDACC Leaders: Denise Scholtens, PhD
• Planned Enrollment: 12,000 system-wide implementation outcomes; 1,000 effectiveness outcomes
• Number of Sites: 7 regional Northwestern clusters of sites
• Publications: Implementation and evaluation of an expanded electronic health record-integrated bilingual electronic symptom management program across a multi-site Comprehensive Cancer Center: The NU IMPACT protocol

The QUARTET USA trial was a randomized clinical trial designed to investigate treatment of hypertension in the Federally Qualified Health Center (FQHC) Access Community Health Network in Chicago, Illinois.

• ClinicalTrials.gov: NCT03640312
• Study Leaders: Mark Huffman, MD, MPH; Jody Ciolino, PhD
• NUDACC Leaders: Jody Ciolino, PhD
• Enrollment: 62 participants
• Number of Sites: 2
• Publications:
  • Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial
  • Process Evaluation of a Double‐Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra‐Low‐Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA)
  • Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial

The SuperAging Research Initiative unites a network of sites across the US and Canada dedicated to identifying the biologic, genetic and psychosocial factors associated with SuperAging. SuperAgers are 80+ year-olds with episodic memory performance that is at least as good as what would be considered normal for 50-60 year-olds. NUDACC is partnering with the SuperAging group for data capture, quality assessment and statistical analyses of cutting-edge genetics, imaging and sensor data.

• Website: www.brain.northwestern.edu/join/SuperAging.html
• Study Leaders: Emily Rogalski, PhD
• NUDACC Leaders: Nathan Gill, PhD; Denise Scholtens, PhD
• Number of Sites: 5
•  Publications:
  • The SuperAging Research Initiative: A multisite consortium focused on identifying factors promoting extraordinary cognitive aging
  • Enrollment and Scientific Progress of the Multisite SuperAging Research Initiative
• Media:
  • 4 Habits of 'SuperAgers'
  • What Makes Someone a SuperAger?

VIVID is a Phase II Study designed to evaluate preliminary efficacy of a novel imaging device to reduce the positive margin rate after surgical resection of breast cancers.

• ClinicalTrials.gov: NCT05545150
• Study Leaders: Swati Kulkarni, MD; Xiao Han, PhD
• NUDACC Leaders: Denise Scholtens, PhD
• Planned Enrollment: 100 participants
• Number of Sites: 4

• Factorial Clinical Trial Designs
  • NUDACC authors: Jody D. Ciolino, Dense M. Scholtens, Lauren B. Bonner
• Covariate-Constrained Randomization
  • NUDACC authors: Jody D. Ciolino, Jacob M. Schauer, Lauren B. Bonner
• Power considerations for the win ratio: A rank-based simulation approach
  • NUDACC authors: Lauren B. Bonner, Jody D. Ciolino, Denise M. Scholtens
• Going beyond the technology: Considerations in translating electronic case report forms
  • NUDACC authors: Amy E. Krefman, Luke V. Rasmussen, Crystal Santillanes, Mary Beth Tull, Patricia Bustamante, Alan Kuang, Lauren B. Bonner, Jody D. Ciolino
• Workflows to automate covariate-adaptive randomization in REDCap via data entry triggers
  • NUDACC authors: Jacob M. Schauer, Luke V. Rasmussen, Jody D. Ciolino

• Guidance on interim analysis methods in clinical trials
  • NUDACC authors: Jody D. Ciolino, Lauren Balmert Bonner

• Society for Clinical Trials
• Website: https://www.sctweb.org/

• UNIversity data COoRdinating ceNters
• Website: https://unicorn-dcc.org/

• Association for Clinical and Translational Science
• Website: https://www.actscience.org/

• American Statistical Association
• Website: https://www.amstat.org/

• Association of Clinical Research Professionals
• Website: https://acrpnet.org/ 

• Society of Clinical Research Associates
• Website: https://www.socra.org/