Drug-gene-nutraceutical Interactions of Cannabidiol and Tacrolimus

NCT05490511 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 127635R01AT011463-02
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The information learned in these studies will help to inform doctors as to how to appropriately adjust doses of cannabidiol and tacrolimus in order to improve health outcomes and long-term treatment success for transplant recipients.

Conditions

Kidney Disease, Chronic; CBD; Transplant Complication

Keywords

cannabidiol; tacrolimus; CYP3A5

Outcome Measures

Primary Outcomes (1)

• The AUC0-Infinity ratio of tacrolimus with cannabidiol divided by tacrolimus alone

  The primary outcome is the AUC0-Infinity ratio of tacrolimus with cannabidiol divided by tacrolimus alone between CYP3A5 expressers and non-expressers in subjects with and without chronic kidney disease (CKD). Subjects with and without CKD will be analyzed separately.

  27 days

Secondary Outcomes (1)

• Immune cell distribution and signaling as measured by scRNA sequencing

  27 days

Study Arms (4)

CYP3A5 expressers without chronic kidney disease

ACTIVE COMPARATOR

Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose

CYP3A5 non-expressers without chronic kidney disease

ACTIVE COMPARATOR

Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose

CYP3A5 expressers with chronic kidney disease

ACTIVE COMPARATOR

Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose

CYP3A5 non-expressers with chronic kidney disease

ACTIVE COMPARATOR

Drug: Tacrolimus single dose; Drug: Epidiolex single dose; Drug: Epidiolex steady-state and tacrolimus single dose

Interventions

Tacrolimus single dose DRUG

5 mg once

Also known as: Period 1

CYP3A5 expressers with chronic kidney disease; CYP3A5 expressers without chronic kidney disease; CYP3A5 non-expressers with chronic kidney disease; CYP3A5 non-expressers without chronic kidney disease

Epidiolex single dose DRUG

Epidiolex 5 mg/kg

Also known as: Period 2

CYP3A5 expressers with chronic kidney disease; CYP3A5 expressers without chronic kidney disease; CYP3A5 non-expressers with chronic kidney disease; CYP3A5 non-expressers without chronic kidney disease

Epidiolex steady-state and tacrolimus single dose DRUG

Epidiolex at up to 5 mg/kg twice daily (for 14 days) and tacrolimus 5 mg once on day 12 of period

Also known as: Period 3

CYP3A5 expressers with chronic kidney disease; CYP3A5 expressers without chronic kidney disease; CYP3A5 non-expressers with chronic kidney disease; CYP3A5 non-expressers without chronic kidney disease

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75
• Are judged healthy enough to participate as determined by and decided from a pre-enrollment screening session that includes medical history and laboratory tests such as blood and urine tests, and electrocardiography (EKG).
• Agree to refrain from taking any prescription medications, over-the-counter medications, and herbal, dietary, and alternative supplements that may interact with the metabolism of the study drugs at least 2 weeks prior to the start of the study and until study completion.
• Are willing to commit the time requested for this study
• Are willing to refrain from smoking or use of tobacco or marijuana for at least two weeks prior to and until the completion of the study (the entire study lasts for approximately 26 days).
• Additional Criteria for the Healthy volunteer study:
• Have a GFR above 60 ml/min/1.73m2 with proteinuria less than 0.3 grams by urine protein to creatinine ratio or 24 hour urine collection
• Additional Criteria for the CKD study:
• Have either:
• A GFR less than or equal to 60 ml/min/1.73m2 or
• The presence of greater than 0.3 grams of proteinuria by urine protein to creatinine ratio or 24 hour urine collection, but less than 3.5 gm of nephrotic range proteinuria as hypoalbuminemia may impact protein binding.

You may not qualify if:

• Unable to provide informed consent
• Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (tacrolimus or cannabidiol);
• Are currently taking sedative agents, including agents for insomnia
• Are underweight (body mass index (BMI) less than 18.5) or overweight \[body mass index (BMI) greater than 35\]
• Have a positive pregnancy serum or urine test obtained just prior to each study, or are breast feeding
• Are night shift workers
• Are on dialysis
• Have compromised liver function as defined by pre-screening bilirubin, AST and ALT testing including any elevation of bilirubin or AST/ALT more than 2x the upper limit of normal.
• Are not willing to refrain from smoking or use of marijuana for at least two weeks prior to and until the completion of the study
• Have a Hgb \< 10.0 g/dL
• Have gastrointestinal (digestive) disorders such as persistent diarrhea or malabsorption that would interfere with the absorption of orally administered drugs
• Have a history of or current seizure disorder
• Are currently on immunosuppression or are immunosuppressed.
• Are recipients of a current allograft (heart, kidney, pancreas, liver, intestine, lung, stem cell transplant).
• Have baseline EKG readings that are abnormal that could place the patient at the high risk.

Sponsors & Collaborators

• Indiana University: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Related Publications (3)

• Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, Wang D, Vinks AA, He Y, Swen JJ, Leeder JS, van Schaik R, Thummel KE, Klein TE, Caudle KE, MacPhee IA. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015 Jul;98(1):19-24. doi: 10.1002/cpt.113. Epub 2015 Jun 3.

  PMID: 25801146 BACKGROUND

• Brown JD, Winterstein AG. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. J Clin Med. 2019 Jul 8;8(7):989. doi: 10.3390/jcm8070989.

  PMID: 31288397 BACKGROUND

• Gisch DL, Koyama S, Etkins J, So GC, Fehrenbach DJ, Lu JBL, Cheng YH, Ferreira RM, Rajadhyaksha E, McClara K, Asghari M, Sharfuddin AA, Dagher PC, Snell LM, Madhur MS, Polidoro RB, Desta Z, Eadon MT. Cannabidiol exerts antiinflammatory effects but maintains T effector memory cell differentiation in humans. JCI Insight. 2025 Nov 18;11(1):e198590. doi: 10.1172/jci.insight.198590. eCollection 2026 Jan 9.

  PMID: 41252210 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Tacrolimus; Cannabidiol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cannabinoids; Terpenes; Hydrocarbons

Study Officials

• Michael Eadon, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

• Zeruesenay Desta, PhD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Subjects participate in a 3-phase fixed sequence pharmacokinetic study to evaluate the interaction between tacrolimus, cannabidiol, and genotype on tacrolimus AUC and immune system pharmacodynamic outcomes. Subjects with and without CKD will be enrolled in parallel arms.

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 5, 2022
• Study Start: October 31, 2022
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: February 13, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)