Drug Interaction Potential of Pro-Inflammatory Conditions

NCT07360938 | Recruiting DMC

• 1 other identifier: 27983
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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 \[PBPK\]).

Conditions

End Stage Renal Disease; Irritable Bowel Syndrome; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Patient Genomic Markers

  Through study completion, up to 2 years post enrollment

Study Arms (3)

Type 2 Diabetes Mellitus

Other: None (Observational)

End Stage Renal Disease

Other: None (Observational)

Irritable Bowel Syndrome

Other: None (Observational)

Interventions

None (Observational) OTHER

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; Irritable Bowel Syndrome; Type 2 Diabetes Mellitus

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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
• Concomitant treatment with systemic immunosuppressant drugs

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Kidney Failure, Chronic; Irritable Bowel Syndrome

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Central Study Contacts

Ross C Robinson

CONTACT

3172742744; rossrobi@iu.edu

Tyler A Shugg, PharmD, PhD

CONTACT

9856304594; tshugg@iu.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 22, 2026
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)