Genomic Resources for Enhancing Available Therapies (GREAT1.0) Study (GREAT1)

This is a prospective, descriptive, observational research study designed to observe and document the clinical practice by domain experts, and how the knowledge of new findings that are published in the medical literature affect clinical decision making.

The study will evaluate risk factors and co-variants, including genetic variants that are associated with disease progression such as pain, inflammation, organ dysfunction, disability and quality of life.

Study Overview

• Status: Suspended
• Conditions: Multiple Sclerosis; Diabetes Mellitus; Chronic Kidney Diseases; Gastritis; Rheumatoid Arthritis; Chronic Pain; Irritable Bowel Syndrome; Hepatitis; Inflammatory Bowel Diseases; Dyslipidemias; Chronic Disease; Celiac Disease; Cholecystitis; Crohn Disease; Cystic Fibrosis; Chronic Pancreatitis; NASH - Nonalcoholic Steatohepatitis; Acute Pancreatitis; Biliary Cirrhosis; Bile Acid Synthesis Defect; Cholelithiases; IPMN; Cyst Pancreas; Pancreatic Exocrine Insufficiency; Diarrhea Chronic; Constipation - Functional; Constipation Chronic Idiopathic
• Intervention / Treatment: Other: venipuncture; Behavioral: Questionnaires; Other: Additional Sample Collections

Detailed Description

The Genomic Resource to Enhance Available Therapies (GREAT1.0) Study is a research program for personalized medicine. It is a highly annotated genetic and biosample resource for multiple nested observational cohort studies. It is designed to begin to understand the mechanisms underlying complex diseases using clinical information from the UPMC electronic health record (EHR), from case-report forms, and from biological samples.

Aim 1. To test the hypothesis that point-of-care electronic health record (EHR)-based phenotyping and clinical measures will be useful for classifying patient by disease risk, subtype, activity, complications, quality of life or using statistical or systems approaches.

Aim 2. To test the hypothesis that common diseases can be subtyped using genotype data.

Aim 3. To test the hypothesis biological samples will provide additional functional and mechanistic information about subject health, disease or state.

The study will be conducted using UPMC patients and population controls. Consent will allow EHR and/or case report form data, plus biological samples to be given a unique code number and transferred to researchers for analysis. Consent will also allow for a secure link to be maintained allowing the research data or samples to be updated, and to contact the clinical team and/or subject to provide them with additional information.

• Study Type: Observational
• Enrollment (Estimated): 120000

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients seen in a UPMC facility with available electronic health records

Description

Inclusion Criteria:

Case Subjects

• Clinical diagnosis of a chronic disease or disorder (ex. pancreatitis, hepatitis or fatty liver, inflammatory bowel disease, irritable bowel syndrome, diarrhea, constipation, chronic pain syndromes, diabetes, hypertension, cardiovascular disease, chronic kidney disease, chronic neurologic disorders, rheumatological disorders, endocrine disorders, chronic pulmonary diseases, sinorespiratory disorders, chronic skin diseases, cancers and related disorders)
• Ability to read and write in English;
• Ability to provide informed consent

Control Subjects

• UPMC patients age 12 years without a chronic disorder.

Exclusion Criteria:

• Chronic infectious disease as the primary medical problem
• Less than 12 years of age
• Inability of the subject to understand the protocol
• Inability to the subject provide informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case/Chronic complex disorders; Chronic complex disorders are composed of multiple population sub classifications - many of which have not been fully defined. Thus, all eligible patients should be included to maximize study power. Sufficient numbers of controls, those individuals in the general population, who may or may not have complex disorders are needed to match future comparison studies for a subset of questions, and so should also be included.	Other: venipuncture; Research blood collection is also an option via venipuncture if the subject is not scheduled for clinical testing. This will also be limited to 21cc of blood, up to 4 time a year, and with the approval of the attending physician.; Behavioral: Questionnaires; PROMIS-43 Profile, PROMIS-29 Profile, Global Health Scale and Hospital Anxiety and Depression Scale (HADS). Additional assessments can be approved and administered per specific disease sub-category.; Other: Additional Sample Collections; We may also contact subjects to request additional blood, saliva, cheek swab, hair, urine, or stool with their permission. This will be limited to no more than 4 teaspoons of blood and will happen no more than 4 times per year.
Control; The number of controls that are anticipated for this study is less than patient numbers since they will not be needed for calculating the minor allele frequency of the majority of genetic polymorphism of interest in genetic association studies. This data is already available in public and research databases. Controls will be useful for evaluating case report form questions, providing assessment of the local genetic pool, and for possibly participating in future studies as provided by the consent.	Other: venipuncture; Research blood collection is also an option via venipuncture if the subject is not scheduled for clinical testing. This will also be limited to 21cc of blood, up to 4 time a year, and with the approval of the attending physician.; Behavioral: Questionnaires; PROMIS-43 Profile, PROMIS-29 Profile, Global Health Scale and Hospital Anxiety and Depression Scale (HADS). Additional assessments can be approved and administered per specific disease sub-category.; Other: Additional Sample Collections; We may also contact subjects to request additional blood, saliva, cheek swab, hair, urine, or stool with their permission. This will be limited to no more than 4 teaspoons of blood and will happen no more than 4 times per year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define the molecular disorders contributing to clinicopathological disease definitions for common complex disorders	Diseases are defined by symptoms and pathologic features in specific tissues. The study uses genetic variants associated with disease to define the underlying genes associated with disease, and uses cell biology methods to understand which mechanisms within the specialized cells lead to disease under specific conditions.	through study completion, an average of 1 year
Define risk factors for disease progression, severity, complications and poor quality of life.	Life-style (e.g. alcohol, smoking, diet, exercise), medications, metabolic, genetic and epigenetic factors alter the features of disease. Nested studies, subgroup analysis, stepwise regression, statistical and machine learning will be used to develop disease models where early intervention may alter disease progression and severity.	through study completion, an average of 1 year
Common disease mechanisms and repurposing of medications.	Many chronic diseases, including inflammatory and autoimmune diseases, have similar disease features that arise in different organs. Harmonization of similar disease processes in different organs will be used to increase study power, and to determine if there is evidence that therapeutic interventions for one disease may be effective in another disease, providing evidences to consider drug repurposing and new treatment approaches.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain profile	Pain is measured using visual analogue scales, pain quality, pattern and interference using standardized questionnaires. Patients with similar disease stages and severity often have markedly different levels of pain. Validated tools will be used to observe responses to disease treatments between similar patients, and to observe factors that may be targetable to lessen pain in future intervention studies.	through study completion, an average of 1 year
Patient Reported Global Health Assessment	PROMIS29 It is a comprehensive measure in that it is assessing multiple aspects of mental, physical, and social health.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Study Chair: David C Whitcomb, MD, PhD, University of Pittsburgh

Publications and helpful links

General Publications

• Whitcomb DC. Primer on Precision Medicine for Complex Chronic Disorders. Clin Transl Gastroenterol. 2019 Jul;10(7):e00067. doi: 10.14309/ctg.0000000000000067.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: fibrosis; chronic inflammation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Lung Diseases; Urologic Diseases; Pain; Neurologic Manifestations; Disease Attributes; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Infant, Newborn, Diseases; Liver Diseases; Renal Insufficiency; Genetic Diseases, Inborn; Gastroenteritis; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Lipid Metabolism Disorders; Malabsorption Syndromes; Gallbladder Diseases; Biliary Tract Diseases; Pancreatic Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Fibrosis; Multiple Sclerosis; Kidney Diseases; Renal Insufficiency, Chronic; Gastritis; Irritable Bowel Syndrome; Chronic Pain; Inflammatory Bowel Diseases; Fatty Liver; Diarrhea; Dyslipidemias; Chronic Disease; Celiac Disease; Non-alcoholic Fatty Liver Disease; Cholecystitis; Crohn Disease; Constipation; Cystic Fibrosis; Pancreatitis; Pancreatitis, Chronic; Cholelithiasis; Liver Cirrhosis, Biliary; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: STUDY19020035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No