Drug Interaction Potential of Pro-Inflammatory Conditions (DIPPIC)

Indiana University

Status

Enrolling

Conditions

Irritable Bowel Syndrome

End Stage Renal Disease

Diabetes Mellitus, Type 2

Treatments

Other: None (Observational)

Study type

Observational

Funder types

Other

Identifiers

NCT07360938

27983

Details and patient eligibility

About

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]).

Enrollment

150 estimated patients

Sex

All

Ages

12 to 99 years old

Volunteers

No Healthy Volunteers

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