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

Suspended

• Conditions: Chronic Pancreatitis; Irritable Bowel Syndrome; Chronic Kidney Diseases; Crohn Disease; Celiac Disease; Cystic Fibrosis; Diarrhea Chronic; Constipation - Functional; Inflammatory Bowel Diseases; Diabetes Mellitus
• Interventions: Other: venipuncture; Behavioral: Questionnaires; Other: Additional Sample Collections

• Registration Number: NCT04306939
• Lead Sponsor: University of Pittsburgh

Brief Summary

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.

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 Timeline

• Study Start: 2014-11-01
• Study First Submitted: 2019-12-16
• Study First Submitted QC: 2020-03-10
• Study First Posted: 2020-03-13
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-08
• Last Update Posted: 2024-07-09
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 120000

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Case/Chronic complex disorders	venipuncture	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.
Case/Chronic complex disorders	Questionnaires	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.
Case/Chronic complex disorders	Additional Sample Collections	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.
Control	venipuncture	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.
Control	Questionnaires	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.
Control	Additional Sample Collections	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.

Primary Outcome Measures

Name	Time	Method
Common disease mechanisms and repurposing of medications.	through study completion, an average of 1 year	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.
Define the molecular disorders contributing to clinicopathological disease definitions for common complex disorders	through study completion, an average of 1 year	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.
Define risk factors for disease progression, severity, complications and poor quality of life.	through study completion, an average of 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Pain profile	through study completion, an average of 1 year	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.
Patient Reported Global Health Assessment	through study completion, an average of 1 year	PROMIS29 It is a comprehensive measure in that it is assessing multiple aspects of mental, physical, and social health.

Trial Locations

Locations (1)

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States