Drug Interaction Potential of Pro-Inflammatory Conditions (DIPPIC)

Pro-inflammatory cytokines, which are elevated in pro-inflammatory disease states (e.g., type II diabetes mellitus [T2DM], irritable bowel diseases [IBD], and end stage renal disease [ESRD]) have been shown to inhibit hepatic drug-metabolizing enzymes, including members of the cytochrome P450 (CYP) family, and drug transporters; resultantly, pro-inflammatory diseases have been demonstrated to increase the exposure and potential for adverse drug events with co-administered CYP and drug transporter substrates. However, the clinical relevance of pro-inflammatory disease-drug interactions has not been systematically evaluated. The long-term goal of this research is to establish clinical strategies to mitigate pro-inflammatory disease-drug interactions and associated adverse drug events. The specific objective of this study is to determine the clinical relevance of pro-inflammatory disease-drug interactions, including establishment of the effect of pro-inflammatory diseases on drug disposition throughout disease trajectories (i.e., determining the differential effects on drug disposition based on the severity of disease). Towards this objective, this study will investigate the extent of increases in inflammation in patients with varying severities of pro-inflammatory diseases and estimate the resulting effects on drug disposition. Cytokine/chemokine concentrations and immune cell profiles will be assayed from blood samples of adult and pediatric patients with differing severities of pro-inflammatory diseases, using established disease monitoring parameters (e.g., glycosylated hemoglobin [HbA1C] for T2DM, C-reactive protein [CRP] for IBD, proteinuria for ESRD). The effect of changes in inflammation during differing severities of these pro-inflammatory diseases on drug disposition will then be estimated using established pharmacokinetic modeling approaches (e.g., physiologically-based pharmacokinetic modeling [PBPK]).

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Irritable Bowel Syndrome; End Stage Renal Disease
• Intervention / Treatment: Other: None (Observational)

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Ross C Robinson; Phone Number: 3172742744; Email: rossrobi@iu.edu
• Study Contact Backup: Name: Tyler A Shugg, PharmD, PhD; Phone Number: 9856304594; Email: tshugg@iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Hospital
      • Contact: Ross Robinson; Phone Number: 3172742744; Email: rossrobi@iu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This is a prospective observational study that will collect blood samples at 1-3 timepoints per patient. The study will not include any therapeutic intervention, and no study visits will involve patient interaction with the health system solely for study participation. The study will enroll up to 150 patients. All enrolled patients will undergo the study procedures, which will enable quantification of plasma cytokine concentrations and immune cell profiles at 1-3 timepoints.

Description

Inclusion Criteria:

• Diagnosed with a pro-inflammatory disease, including T2DM, IBD, and ESRD
• Ability to provide written informed consent and HIPAA authorization

Exclusion Criteria:

• Diagnosis or past medical history of non-IBD autoimmune disorder, including systemic lupus erythematosus, Sjogren's syndrome, multiple sclerosis, type 1 diabetes mellitus, Behcet's disease, and ankylosing spondylitis
• Current infection requiring medical treatment (note: if a prospective patient's infection resolves, they can be re-screened for trial inclusion)
• Concomitant treatment with systemic immunosuppressant drugs

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Type 2 Diabetes Mellitus	Other: None (Observational); This observational study will not involve any interventions. Instead, the study will collect blood samples at one or multiple time points.
End Stage Renal Disease	Other: None (Observational); This observational study will not involve any interventions. Instead, the study will collect blood samples at one or multiple time points.
Irritable Bowel Syndrome	Other: None (Observational); This observational study will not involve any interventions. Instead, the study will collect blood samples at one or multiple time points.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of Plasma Cytokine Concentrations	The first primary objective will involve quantification of plasma cytokine concentrations from patient blood samples.	Through study completion, up to 2 years post enrollment
Phenotyping of Patient Immune Cells	The second primary objective will involve phenotyping of patient immune cells from patient blood samples.	Through study completion, up to 2 years post enrollment
Quantification of the Plasma Concentrations of Endogenous Biomarkers of Drug Metabolism and Transport	The third primary objective will involve quantification of the plasma concentrations of endogenous biomarkers of drug metabolism and transport from patient blood samples	Through study completion, up to 2 years post enrollment
Measures of Inflammatory Disease Severity	The fourth primary objective will involve collecting measures of inflammatory disease severity based on information collected from patients' electronic health records.	Through study completion, up to 2 years post enrollment
Development of Adverse Events Attributable to CYP/Transporter Substrate Medications	The fifth primary objective will involve collecting the development of adverse drug events attributable to CYP/transporter substrate medications based on information collected from patients' electronic health records.	Through study completion, up to 2 years post enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Genomic Markers	The secondary objective will involve determining patient genomic markers (using whole genome sequencing).	Through study completion, up to 2 years post enrollment

Collaborators and Investigators

• Sponsor: Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 14, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Colonic Diseases; Renal Insufficiency; Colonic Diseases, Functional; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Irritable Bowel Syndrome; Diabetes Mellitus, Type 2; Kidney Failure, Chronic
• Other Study ID Numbers: 27983

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There are Material Transfer Agreements and Data Use Agreements in place to share IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No