Exploring how yohimbine is processed in men and women based on genetics
Kinetics of Yohimbine in Humans to Explore Sex and CYP2D6 Genotype Interactions - YOKI-1 Study
This study is testing how different people process yohimbine based on their sex and genetics to see how it affects their bodies.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years to 40 Years |
| Sex | All |
| Sponsor | University Medicine Greifswald Academic / other |
| Locations | 1 site (Greifswald, Mecklenburg-Vorpommern) |
| Trial ID | NCT06939608 on ClinicalTrials.gov |
What this trial studies
This study investigates how yohimbine is metabolized in healthy volunteers aged 18 to 40, focusing on sex-specific differences and genetic variations in the CYP2D6 enzyme. Participants will be categorized into four groups based on their sex and CYP2D6 genotype, receiving a single oral dose of yohimbine and ¹³C₃-caffeine. Blood and urine samples will be collected at various time points to analyze the pharmacokinetics of yohimbine and its metabolites. The study aims to assess yohimbine's effectiveness as a probe for evaluating CYP2D6 activity and to explore interactions with other metabolic pathways.
Who should consider this trial
Good fit: Ideal candidates are healthy men and women aged 18 to 40 who are classified as either extensive or poor metabolizers based on their CYP2D6 genotype.
Not a fit: Patients with a BMI outside the range of 18 to 30 kg/m² or those with significant health issues may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could enhance personalized medicine by improving our understanding of how genetic factors influence drug metabolism.
How similar studies have performed: While studies on pharmacogenetics are common, this specific investigation into yohimbine's pharmacokinetics based on sex and CYP2D6 genotype is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. individuals of both biological sexes, assigned as women or men at birth 2. age: ≥ 18 and ≤ 40 years 3. possesses the ability to understand the study purpose and design 4. contractually capable and provides signed informed consent form 5. in good general health or with mild and/or well-managed conditions such as allergies, asthma, hypertension or orthopedic diseases 6. taking no more than three chronic medications 7. individuals classified as either extensive metabolizers (EM) or poor metabolizers (PM) based on their CYP2D6 genotype: Extensive Metabolizers (EM): homozygous for CYP2D6 \*1,CYP2D6 \*2, CYP2D6 \*35, or heterozygous combination of any of these alleles Poor Metabolizers (PM): homozygous for CYP2D6 \*3, CYP2D6 \*4, CYP2D6 \*5, CYP2D6 \*6, or heterozygous combination of any of these alleles Exclusion Criteria: 1. BMI \> 30 kg/m2 and \< 18 kg/m2 2. body weight \< 48 kg 3. women: known pregnancy or lactation period; positive urine pregnancy test at screening or kinetic visit 4. men: hemoglobin \< 13 g/dl (8,07 mmol/l) women: hemoglobin \< 12 g/dl (7,45 mmol/l) 5. elevated liver function tests (1 or more of ALAT, ASAT, yGT, Bilirubin \> 2x ULN) 6. reduced renal function (eGFRMDRD \< 60 mL/min/1,7 m2) 7. QTcF \> 450 ms in screening ECG 8. current or recent psychiatric disorders requiring treatment including depression, bipolar disorder, schizophrenia, psychosis or severe anxiety disorders 9. drug dependency at the time of visit 10. use of recreational drugs more than twice a week 11. any known hypersensitivity or allergic reactions to yohimbine or caffeine 12. history of severe hypersensitivity reactions and/or anaphylaxis 13. poor venous conditions that make it impossible to place a peripheral venous catheter and regularly draw blood through it o) intake of drugs interfering with CYP2D6 and/or CYP1A2 during the past seven days p) intake of yohimbine within 48 hours and caffeine within 16 hours prior to study participation q) engagement in extreme physical activity within 48 hours prior to study participation
Where this trial is running
Greifswald, Mecklenburg-Vorpommern
- University Medicine Greifswald, Institute of Pharmacology — Greifswald, Mecklenburg-Vorpommern, Germany (Recruiting)
Study contacts
- Study coordinator: Stefan Engeli, Prof. Dr.
- Email: stefan.engeli@med.uni-greifswald.de
- Phone: +49 3834 86 5633
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.