Clinical Research Directory

KF2025#1 Trial: Ketamine, Cannabidiol and Cobicistat Interaction Study

Ketamine is a dissociative anesthetic developed approximately 60 years ago. Both ketamine and its isomer, esketamine, have been used for over 20 years in the treatment of treatment-resistant depression. Other treatment options for this type of depression include combinations of antidepressants, other medications used in depression treatment (such as lithium), psychotherapy, electroconvulsive therapy, and repetitive transcranial magnetic stimulation. The advantage of ketamine and its stereoisomer, esketamine, over other treatment options is their rapidly emerging antidepressant effect, which becomes apparent within the first few days of treatment. Ketamine is primarily metabolized by the cytochrome P450 (CYP) 3A4 enzyme, but also by the CYP2B6 and CYP2C9 enzymes. However, information on the significance of these different enzymes in ketamine metabolism is incomplete. Due to extensive first-pass metabolism, the bioavailability of orally administered ketamine varies significantly and is, on average, only 8-24%. This makes ketamine unsuitable for oral administration. In the treatment of depression, ketamine is administered as a slow intravenous infusion. The concurrent use of medications that inhibit ketamine metabolism can significantly increase the bioavailability of orally administered ketamine. Cobicistat is a potent inhibitor of the CYP3A4 enzyme, which can significantly increase ketamine bioavailability and reduce interindividual variability by inhibiting ketamine's CYP3A4-mediated metabolism. This might enable the oral use of ketamine. Cannabidiol is a cannabinoid that does not have addictive effects, but may have antidepressant and anxiolytic effects. Cannabidiol might reduce the dissociative side effects associated with ketamine treatment. Clinically, cannabidiol appears to moderately inhibit CYP enzymes in the order of potency: CYP2C19 \> CYP2C9 \> CYP3A \> CYP1A2, and based on in vitro data, it also somewhat inhibits the CYP2B6 enzyme, which is involved in ketamine metabolism. However, its effect on ketamine concentrations cannot be assessed based on current knowledge. The purpose of this study is to investigate the potential effects of cannabidiol, cobicistat, and their concurrent administration on the pharmacokinetics of orally administered ketamine. A secondary objective is to study the effect of cannabidiol on ketamine-induced side effects. Study Methodology: This is a four-phase, randomized, open-label, crossover study involving 12 healthy volunteers. On study days, participants will receive a 56 mg oral dose of ketamine in the research facility, alternately with water, cannabidiol, cobicistat, or both cannabidiol and cobicistat. There will be at least a two-week washout period between study days. The pharmacokinetics of ketamine and other study drugs will be investigated by taking blood samples according to a separate schedule for 11 hours after administration on the study day and the following morning. Pharmacokinetic parameters will be calculated from plasma concentrations of ketamine, cobicistat, cannabidiol, and their metabolites. The primary outcome measure is the total area under the curve (AUC0-∞) of ketamine. Additionally, the effects of the drugs on blood pressure, heart rate, and subjective adverse feeling of the study participants will be examined.

Association Between Geriatric Frailty and Medication Related Problems in the Emergency Department to Help Clinical Pharmacists Prioritise Patients

The healthcare systems are under increasing pressure due to a rise in emergency consultations, staff shortages, an ageing population and rising costs. Emergency departments are seeing more vulnerable patients, including elderly people, who are often on multiple medications and at risk of medication errors. To improve safety, the integration of pharmacists specialising in emergency medicine has proven beneficial: their presence in the team improves the detection of medication-related problems, speeds up and optimises treatment, reduces rehospitalisations and lowers healthcare costs. However, in most countries, these pharmacists are still rarely found in emergency departments, mainly due to a lack of resources and clinical prioritisation criteria tailored for them and adapted to this environment. Frailty screening tools and scores, such as ISAR, can be used to identify the elderly patients most at risk, predict adverse events such as fall or mortality, and thus adapt their care in the emergency department. Indeed, elderly frail patients often take many medications and consequently are at risk of medication errors, adverse events, inappropriate prescriptions or serious drug interactions. These patients may therefore require a specialised review on their medication by clinical pharmacists when they are admitted to the emergency department, but their high number make it impossible to care for all of them. We aim thus to evaluate the association between frailty (according to the ISAR score) and medication-related problems among elderly patients admitted to the emergency department. Researchers will examine whether this score can predict the presence of inappropriate prescribing and high-risk drug interactions. If so, pharmacists would then have a quick and easy tool to prioritise patients who would benefit most from a specialised review of their medications when they visit the emergency department. There will not be any intervention and this study will not influence patients care. Once patients agree to participate, researchers will prospectively collect medical data from elderly patients admitted to the emergency department and analyse their medical history, home medication, reason for admission, frailty score using ISAR, and perform a pharmaceutical analysis based on these data.

B-free Multistage Trial

The primary objective of the study is to evaluate the efficacy of a booster-free regimen including DOR/DTG/3TC among HIV-suppressed PLWH with previous virological failure. The key secondary objectives are i) to determine whether switching to DOR / DTG / 3TC leads to lower burden of DDI compared to continuing a booster-containing regimen, and ii) to assess changes in patient perception on treatment acceptability and satisfaction, as well as health-related quality of life after a switch to booster-free ART. Qualitative sub-study: Qualitative objectives will be met using semi-structured interviews. Thirty people (15 from the intervention arm, 15 from the control arm) will be interviewed twice, at week 0 and week 48. Additional 15 individuals from the observational cohort will be interviewed once. Interviews will take place following study visits and performed using semi-structured guides. The guide for the interviews at week 48 will be based on results from analyses of the interviews conducted at week 0.