Clinical trial NCT03687073: Trial of Indole-3-Carbinol and Silibinin
Official title: Trial of Indole-3-Carbinol & Silibinin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Smoking
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2018-09-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety of the combination of I3C + Sil
timeFrame: Week 8
measure: Pharmacokinetic profile of I3C + Sil
timeFrame: Week 8
measure: Pharmacokinetic profile of I3C + Sil
timeFrame: Week 8
measure: Pharmacokinetic profile of I3C + Sil
timeFrame: Week 8
measure: Pharmacokinetic profile of I3C + Sil
timeFrame: Week 8
measure: Pharmacokinetic profile of I3C + Sil
timeFrame: Week 8
measure: Pharmacokinetic profile of I3C + Sil
timeFrame: Week 8
measure: Pharmacokinetic profile of I3C + Sil
timeFrame: Week 8
Secondary outcomes:
measure: Effect of I3C, Sil, or I3C + Sil on circulating inflammatory markers
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on circulating immunophenotype
timeFrame: Week 8
measure: 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)
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on RNA sequencing from PBMC
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in buccal cells
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in oral cavity cells
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in nasal mucosa
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on fasting glucose
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on fasting insulin
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on lipid profile
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on leptin
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on body weight
timeFrame: Week 8
measure: Effect of I3C, Sil, or I3C + Sil on waist circumference
timeFrame: Week 8
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota
name: Naomi Fujioka, MD
role: PRINCIPAL_INVESTIGATOR
References: