What side effects are associated with this type of intervention?

Tacrolimus, an immunosuppressant used to prevent organ rejection, can cause nephrotoxicity, hyperglycemia, hypertension, neurotoxicity, and an increased risk of infections. Cannabidiol, known for its anti-inflammatory and immunomodulatory effects, is generally well-tolerated but may cause diarrhea, somnolence, fatigue, and elevated liver enzymes, particularly at high doses or when combined with other medications.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of transplant rejection, focusing primarily on immunosuppressants. Tacrolimus, cyclosporine, and sirolimus are key FDA-approved immunosuppressants used to prevent organ rejection. These drugs work by inhibiting the immune response that can lead to graft rejection. While cannabidiol, known for its anti-inflammatory and immunomodulatory effects, is not specifically FDA-approved for transplant rejection, it has shown potential in managing immune responses and inflammation, which are critical in the context of organ transplantation.

What other types of research exist?

Promising novel alternatives to Cannabidiol and Tacrolimus for transplant rejection patients include Sirolimus and Belatacept. Sirolimus is effective in reducing malignancies and nonmelanoma skin cancer, while Belatacept has shown long-term efficacy and safety in kidney transplantation.

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Cannabinoid

Cannabidiol + Tacrolimus for Transplant Rejection

Phase 1

Recruiting

Led By Michael Eadon, MD

Research Sponsored by Indiana University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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 (for Healthy volunteer study)

Age 18-65

Must not have

Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (tacrolimus or cannabidiol)

Are underweight (body mass index (BMI) less than 18.5) or overweight (body mass index (BMI) greater than 35)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 27 days

Awards & highlights

No Placebo-Only Group

Summary

This trial aims to understand how CBD, a cannabis compound, interacts with tacrolimus, a drug used by organ transplant patients to prevent rejection. Researchers will study these interactions to see if CBD affects the safety and effectiveness of tacrolimus. Tacrolimus is a strong medication used to prevent organ rejection in transplant patients, with precise dosing requirements. The goal is to help doctors adjust doses of both substances to improve patient health and long-term treatment success.

Who is the study for?

This trial is for adults aged 18-65 with either healthy kidneys or chronic kidney disease, not on dialysis. Participants must avoid certain medications, supplements, and substances like tobacco and marijuana that affect the study drugs' metabolism for two weeks before and during the study. Pregnant or breastfeeding individuals, those with compromised liver function, a history of drug abuse or intolerance to study drugs are excluded.

What is being tested?

The trial investigates how cannabidiol (Epidiolex) interacts with tacrolimus in people who have received transplants. It aims to find safe dosing levels that could improve health outcomes by studying single doses of each drug alone and together at steady-state conditions.

What are the potential side effects?

Potential side effects may include digestive issues due to Epidiolex; tacrolimus might cause problems such as high blood pressure, shaking hands, kidney problems, headaches, diarrhea, abdominal pain, insomnia or tingling in hands/feet.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function is good and I have low protein in my urine.

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I am between 18 and 65 years old.

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I agree not to take any medications or supplements that could affect the study drugs starting 2 weeks before the study.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am allergic or have had bad reactions to tacrolimus or cannabidiol.

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My BMI is either below 18.5 or above 35.

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My kidney function is very low or I am on dialysis.

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My liver tests show bilirubin or enzymes more than twice the normal limit.

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I do not have ongoing stomach issues that affect how I absorb pills.

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I am currently taking medication for sleep or anxiety.

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I am unable to understand and give consent for treatment.

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I have the CYP3A4 *22/*22 genotype.

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I have a history of seizures or currently experience them.

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I am currently taking medication that weakens my immune system.

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I have received an organ or stem cell transplant.

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I was hospitalized unexpectedly at least once in the past 6 months or twice in the past 2 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 27 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~27 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 27 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

Immune cell distribution and signaling as measured by scRNA sequencing

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Active Control

Group I: CYP3A5 expressers without chronic kidney diseaseActive Control3 Interventions

Group II: CYP3A5 non-expressers without chronic kidney diseaseActive Control3 Interventions

Group III: CYP3A5 expressers with chronic kidney diseaseActive Control3 Interventions

Group IV: CYP3A5 non-expressers with chronic kidney diseaseActive Control3 Interventions

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Tacrolimus is a calcineurin inhibitor that works by suppressing the immune system, specifically by inhibiting T-cell activation, which is essential in preventing organ rejection. Cannabidiol, while not a standard treatment for transplant rejection, has shown anti-inflammatory and immunomodulatory effects that could help in reducing inflammation and modulating immune responses. These mechanisms are vital for transplant rejection patients as they help in maintaining the transplanted organ's function and improving long-term health outcomes by preventing the immune system from attacking the new organ.

Tacrolimus. A review of its pharmacology, and therapeutic potential in hepatic and renal transplantation.Late presentation of posterior reversible encephalopathy syndrome following liver transplantation in the setting of tacrolimus and cannabis use.