Smoking
Conditions
Brief summary
This is a non-therapeutic, Phase 1 clinical trial to examine the safety, pharmacokinetic (PK) characteristics, and pharmacodynamics (PD) effect of indole-3-carbinol (I3C) and silibinin (Sil) in healthy subjects.
Interventions
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Adult ≥ 18 years old * Current smoker of ≥ 8 cigarettes per day for at least the last 6 months by self-report * Adequate blood counts, and adequate liver and kidney function defined as follows: * Hemoglobin ≥ 9 g/dL for women, ≥ 10 g/dL for men * Platelet count ≥ 100 x 10\^9/L * Total bilirubin ≤ Institutional upper limit of normal (≤ 1.3 mg/dL for UMMC) * ALT ≤ 1.5 times institutional upper limit of normal * Creatinine ≤ 1.4 g/dL and estimated GFR ≥ 80 mL/min/1.7m2 * Able to understand the experimental nature of the study and provide informed written consent
Exclusion criteria
* Chronic proton pump inhibitor, H2-blocker (i.e., ranitidine, famotidine), and/or calcium carbonate use * History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect gastric or intestinal absorption of nutrients * Current use of tobacco products other than cigarettes (i.e. snuff, snuz, smokeless tobacco, cigars, pipes), or use of these products within 3 months of study registration * Major or chronic medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator * Known active malignancy * History of aerodigestive malignancies * Women who are pregnant, intend to become pregnant within 3 months of study registration, or who are lactating. Women of childbearing potential must have a negative urine pregnancy test within 14 days of starting the assigned intervention * Antibiotic use within 2 months of study registration by self-report * History of respiratory tract cancer * Known allergy to I3C, Sil, or its components * Psychiatric and/or social situations that would potentially limit compliance with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of the combination of I3C + Sil | Week 8 | Incidence of Dose Limiting Toxicities (DLTs) |
| Pharmacokinetic profile of I3C + Sil | Week 8 | AUC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of I3C, Sil, or I3C + Sil on protein expression of phosphorylated-Akt (pAkt), pERK, pSTAT3 and NF-kB from peripheral blood mononuclear cells (PBMC) | Week 8 | Change in protein expression of phosphorylated-Akt (pAkt), pERK, pSTAT3 and NF-kB from peripheral blood mononuclear cells (PBMC) |
| Effect of I3C, Sil, or I3C + Sil on RNA sequencing from PBMC | Week 8 | Change in of I3C, Sil, or I3C + Sil on |
| Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in buccal cells | Week 8 | Change in PIK3CA pathway signaling in buccal cells |
| Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in oral cavity cells | Week 8 | Change in PIK3CA pathway signaling in oral cavity cells |
| Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in nasal mucosa | Week 8 | Change in PIK3CA pathway signaling in nasal mucosa |
| Effect of I3C, Sil, or I3C + Sil on circulating inflammatory markers | Week 8 | Change in inflammatory markers IL-1B, TNF-a, IL-6, IL-8, Cox-2, prostaglandin E, and C-reactive protein |
| Effect of I3C, Sil, or I3C + Sil on fasting insulin | Week 8 | Change in fasting insulin |
| Effect of I3C, Sil, or I3C + Sil on lipid profile | Week 8 | Change in lipid profile |
| Effect of I3C, Sil, or I3C + Sil on leptin | Week 8 | Change in leptin |
| Effect of I3C, Sil, or I3C + Sil on body weight | Week 8 | Change in body weight |
| Effect of I3C, Sil, or I3C + Sil on waist circumference | Week 8 | Change in waist circumference |
| Effect of I3C, Sil, or I3C + Sil on fasting glucose | Week 8 | Change in fasting glucose |
| Effect of I3C, Sil, or I3C + Sil on circulating immunophenotype | Week 8 | Change in circulating immunophenotype |
Countries
United States
Outcome results
None listed