Evaluating the Pharmacokinetics and Drug Interaction Potential of the Botanical Dietary Supplement Cinnamon

NCT05157672 | Unknown Early Phase 1 FDA Drug

• 2 other identifiers: 18686U54AT008909
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate a well-characterized, commercially available cinnamon dietary supplement as a precipitant of pharmacokinetic interactions with cytochrome P450 (CYP) 2A6 drug substrates in healthy volunteers. Nicotine gum will be used as the CYP2A6 probe drug (i.e., positive control) and letrozole as a high-impact object drug. Results will be used to inform future research on the potential use of cinnamon as a smoking cessation agent, as well as the clinical impact on pharmacotherapeutic regimens involving letrozole in cancer patients.

Conditions

Interaction Drug Food

Keywords

pharmacokinetics; interaction; cinnamon; letrozole; nicotine; cinnamaldehyde; cinnamomum verum; natural product

Outcome Measures

Primary Outcomes (1)

• Nicotine area under the concentration vs. time curve (AUC) ratio (exposure/baseline)

  Ratio of the AUC of nicotine in the presence to absence of cinnamon.

  0-12 hours

Secondary Outcomes (8)

• Cinnamon constituent area under the concentration vs. time curve (AUC)

  0-48 hours

• Cinnamon constituent maximum concentration (Cmax)

  0-48 hours

• Cinnamon constituent half-life

  0-48 hours

• Cinnamon renal clearance

  0-24 hours

• Letrozole area under the concentration vs. time curve (AUC) ratio (exposure/baseline)

  0-240 hours

Study Arms (5)

Cinnamon

EXPERIMENTAL

Arm 1 will consist of administration of a single dose of cinnamon (2 g) with water by mouth to 6 subjects (3 biological men, 3 biological women). Blood will be drawn from 0-48 hours. Urine will be collected from 0-24 hours. The subjects may or may not elect to participate in Arms 2-5. If they do, a washout of at least 7 days will occur between Arm 1 administration of cinnamon and the Arm 2 administration of nicotine.

Dietary Supplement: Cinnamon (2 g)

Nicotine

EXPERIMENTAL

Arm 2 will consist of administration of a single dose of nicotine gum (2 mg) to 16 subjects (8 biological men, 8 biological women). If these subjects participated in Arm 1, they will have completed a washout of 7 days since administration of cinnamon before starting Arm 2. Blood and urine will be collected from 0-12 hours relative to nicotine administration. Participants will undergo a washout of at least 4 days before beginning Arm 3.

Drug: Nicotine gum (2.5 mg)

Letrozole

EXPERIMENTAL

Arm 3 will consist of administration of a single oral dose of letrozole (2.5 mg) to the same 16 subjects who participate in Arm 2. Blood and urine will be collected from 0-240 hours and 0-24 hours, respectively, relative to letrozole administration. Participants will undergo a washout of at least 14 days before beginning Arm 4.

Drug: Letrozole (2.5 mg)

Cinnamon + Nicotine

EXPERIMENTAL

The same 16 subjects will self-administer the cinnamon product (2 g) three times daily for five consecutive days. On the sixth day, subjects will be administered cinnamon (2 g) and nicotine gum (2 mg). Cinnamon will be administered two additional times. Blood and urine will be collected from 0-12 hours relative to nicotine administration. Participants will undergo a washout of at least 4 days before beginning Arm 5.

Dietary Supplement: Cinnamon (2 g); Drug: Nicotine gum (2.5 mg)

Cinnamon + Letrozole

EXPERIMENTAL

The same 16 subjects will self-administer the cinnamon product (2 g) three times daily for five consecutive days. On the sixth day, subjects will be administered cinnamon (2 g) and letrozole (2.5 mg). Cinnamon will be administered two additional times. Blood and urine will be collected from 0-240 hours and 0-24 hours, respectively, relative to letrozole administration.

Dietary Supplement: Cinnamon (2 g); Drug: Letrozole (2.5 mg)

Interventions

Cinnamon (2 g) DIETARY_SUPPLEMENT

oral capsules, 2 g

Cinnamon; Cinnamon + Letrozole; Cinnamon + Nicotine

Nicotine gum (2.5 mg) DRUG

gum, 2.5 mg

Also known as: Nicorette

Cinnamon + Nicotine; Nicotine

Letrozole (2.5 mg) DRUG

tablet, 2.5 mg

Also known as: Femara

Cinnamon + Letrozole; Letrozole

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Biological men and women, aged from 18-64 years and healthy
• Not taking any medications (prescription and non-prescription) or dietary/herbal supplements known to alter the pharmacokinetics of either study drug or cinnamon constituents
• Willing to abstain from consuming dietary/herbal supplements and citrus juices for several weeks
• Willing to abstain from consuming caffeinated beverages or other caffeine-containing products the evening before and morning of the first day of a study arm
• Willing to abstain from consuming any alcoholic beverages for one day prior to any study day, during the 14-hour inpatient days, and for the outpatient visit(s) following the 14-hour visit
• Willing to use an acceptable method of contraception that does not include oral contraceptive pills or patches (such as abstinence, copper IUD, condom)
• Have the time to participate
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for the subject to comply with the requirements of the study

You may not qualify if:

• Under the age of 18 or 65+ years
• Any current major illness or chronic illness such as (but not limited to) kidney disease, hepatic disease, diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, cancer, or HIV/AIDS
• History of anemia or any other significant hematologic disorder
• History of drug or alcohol addiction or major psychiatric illness
• Pregnant or nursing
• History of allergy to cinnamon, letrozole, or nicotine
• Taking concomitant medications, both prescription and non-prescription (including dietary supplements/herbal products), known to alter the pharmacokinetics of either study drug or cinnamon constituents
• Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data
• Recreational drug use such as amphetamines, benzodiazepines, cocaine, marijuana, MDMA, opioids, and PCP
• History of intolerance to cinnamon
• Out-of-range clinical laboratory value that the study physician considers participation in the study a health risk

Sponsors & Collaborators

• Washington State University: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• Office of Dietary Supplements (ODS): collaborator

Study Sites (1)

Washington State University College of Pharmacy and Pharmaceutical Sciences

Spokane, Washington, 99202, United States

Location

Related Publications (6)

• Smith T, Majid F, Eckl V, and Reynolds CM (2021) Herbal Supplement Sales in US Increase by Record-Breaking 17.3% in 2020. HerbalGram 131:52-65.

  BACKGROUND

• Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD007170. doi: 10.1002/14651858.CD007170.pub2.

  PMID: 22972104 BACKGROUND

• Chan J, Oshiro T, Thomas S, Higa A, Black S, Todorovic A, Elbarbry F, Harrelson JP. Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. Drug Metab Dispos. 2016 Apr;44(4):534-43. doi: 10.1124/dmd.115.067942. Epub 2016 Feb 5.

  PMID: 26851241 BACKGROUND

• Espiritu MJ, Chen J, Yadav J, Larkin M, Pelletier RD, Chan JM, Gc JB, Natesan S, Harrelson JP. Mechanisms of Herb-Drug Interactions Involving Cinnamon and CYP2A6: Focus on Time-Dependent Inhibition by Cinnamaldehyde and 2-Methoxycinnamaldehyde. Drug Metab Dispos. 2020 Oct;48(10):1028-1043. doi: 10.1124/dmd.120.000087. Epub 2020 Aug 12.

  PMID: 32788161 BACKGROUND

• FDA (2020) Drug Interactions: Relevant Regulatory Guidance and Policy Documents

  BACKGROUND

• Paine MF, Shen DD, McCune JS. Recommended Approaches for Pharmacokinetic Natural Product-Drug Interaction Research: a NaPDI Center Commentary. Drug Metab Dispos. 2018 Jul;46(7):1041-1045. doi: 10.1124/dmd.117.079962. Epub 2018 May 7.

  PMID: 29735755 BACKGROUND

MeSH Terms

Interventions

Nicotine Chewing Gum; Letrozole

Intervention Hierarchy (Ancestors)

Chewing Gum; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Tobacco Use Cessation Devices; Therapeutics; Candy; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: December 15, 2021
• Study Start: December 14, 2021
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2024
• Last Updated: December 7, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)