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.
The commercial availability of cannabidiol, or CBD oil, has increased in the United Stated and this supplement has the potential to cause a variety of drug-drug interactions, including in solid organ transplant recipients who receive tacrolimus to prevent rejection. Through a series of pharmacokinetic and pharmacodynamics assays, this proposal will identify gene-drug and drug-drug interactions (DDI), including those that place transplant recipients at risk for increased toxicity related to their immunosuppression. The information learned in these studies will help to inform practitioners as to whether cannabidiol needs to be avoided in transplant recipients and how to appropriately adjust doses of CBD and immunosuppression in order to improve health outcomes and long-term treatment success in this high-risk population.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
57
5 mg once
Epidiolex 5 mg/kg
Epidiolex at up to 5 mg/kg twice daily (for 14 days) and tacrolimus 5 mg once on day 12 of period
IU Health University Hospital
Indianapolis, Indiana, United States
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.
Time frame: 27 days
Immune cell distribution and signaling as measured by scRNA sequencing
Immune cell distribution and signaling as measured by scRNA sequencing. The hypothesis tested is that cannabidiol will induce T regulatory lymphocytes (Tregs) and reduce overall cytokine signaling as compared to tacrolimus alone. Period 1 and Period 3 will be compared.
Time frame: 27 days
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