Evaluation of Solanidine as an Exogenous Biomarker to Phenotype CYP2D6 Activity in Humans

NCT07817030 | Not Yet Recruiting

• 1 other identifier: IPHA-2026-12
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the evaluation of solanidine as an exogenous biomarker to phenotype CYP2D6-activity in humans. Participants will be classified by their CYP2D6 genotype into poor metabolizers (PM), low intermediate metabolizers (LIM), extensive metabolizers (EM) and ultra-rapid metabolizers (UM), forming four distinct study arms: Arm 1) Poor Metabolizers (PM) n=10 Arm 2) Low Intermediate Metabolizers (LIM) n=5 Arm 3) Extensive Metabolizers (EM) n=10 Arm 4) Ultra-rapid Metabolizers (UM) n=5 Participants will be given a standardized potato-rich meal, serving as the natural source of solanidine, and will be phenotyped for CYP2D6 activity with a single oral microdose of the probe drug yohimbine. The objectives of the study are as follows:

1. 1.To evaluate the suitability of the SSDA/solanidine and m414/solanidine metabolic ratio as an exogenous biomarker to phenotype CYP2D6 activity in humans.
2. 2.To characterize the postprandial plasma concentration profile of solanidine, its CYP2D6-dependent metabolites, and its parent molecules α-solanine and α-chaconine following a potato-rich meal.

Conditions

Pharmacokinetic Study in Healthy Volunteers

Keywords

genetic polymorphisms; pharmacokinetics; CYP2D6; yohimbine; drug metabolism; solanidine

Outcome Measures

Primary Outcomes (1)

• Metabolic ratio of SSDA/solanidine

  This study determines the sensitivity of the metabolic ratio of SSDA/solanidine and the metabolic ratio of m414/solanidine to correctly identify the CYP2D6 metabolizer status. Each MR will be considered separately in order to identify the most suitable one. As we will recruit individuals from the lowest and highest level of CYP2D6 activity, we will test the sensitivity independently for the prediction of the lowest activity level (PM + LIM) and the highest activity level (EM + UM). The "true" CYP2D6 metabolizer status will be determined by the combination of the CYP2D6 genotype and the yohimbine-determined phenotype in recruited individuals. Those individuals with a perfect match of genotype and phenotype are considered the controls to which the solanidine results are then compared as the ratio of phenotype predicted (by solandine MR)/ phenotype determined (by genotyping + yohimbine-phenotyping)

  From enrollment to 60 hours after eating the potato-rich meal.

Secondary Outcomes (3)

• AUC for solanidine, SSDA, m414, α-solanine and α-chaconine

  60 hours

• Cmax for solanidine, SSDA, m414, α-solanine and α-chaconine

  60 hours

• Tmax for solanidine, SSDA, m414, α-solanine and α-chaconine

  60 hours

Study Arms (4)

Poor Metabolizers (PM):

ACTIVE COMPARATOR

Participants in this arm are classified as poor metabolizers (PM, Gene-Score 0) based on their CYP2D6 genotype. Poor metabolizers are homozygous or compound heterozygous for CYP2D6 \*3, CYP2D6 \*4, CYP2D6 \*5, CYP2D6 \*6. Participants were selected to achieve best matching between arms according to age, BMI, alcohol consumption and smoking.

Dietary Supplement: Yohimbine; Other: Consumption of a defined potato-rich meal

Low Intermediate Metabolizer (LIM)

ACTIVE COMPARATOR

Low intermediae metabolizers (LIM, Gene-Score 0,25 or 0,5) are homozygous or compound heterozygous for CYP2D6 \*9, \*10, \*41 or compound heterozygous with one allele of CYP2D6 \*3, CYP2D6 \*4, CYP2D6\*5, or CYP2D6 \*6 and one allele of CYP2D6 \*17 (0,5) or CYP2D6 \*9, \*10, or \*41 (0,25). Participants were selected to achieve best matching between arms according to age, BMI, alcohol consumption and smoking.

Dietary Supplement: Yohimbine; Other: Consumption of a defined potato-rich meal

Extensive Metabolizer (EM)

ACTIVE COMPARATOR

Extensive Metabolizer (EM, Gene-Score 2) are homozygous or compound heterozygous for CYP2D6 \*1, CYP2D6 \*2, CYP2D6\*35. Participants were selected to achieve best matching between arms according to age, BMI, alcohol consumption and smoking.

Dietary Supplement: Yohimbine; Other: Consumption of a defined potato-rich meal

Ultrarapid Metabolizer

ACTIVE COMPARATOR

Ultrarapid Metabolizer (UM, Gen-Score ≥ 3) are homozygous or compound heterozygous for CYP2D6 \*1, CYP2D6 \*2, CYP2D6\*35 with at least one allele duplicated or multiplied. Participants were selected to achieve best matching between arms according to age, BMI, alcohol consumption and smoking.

Dietary Supplement: Yohimbine; Other: Consumption of a defined potato-rich meal

Interventions

Yohimbine DIETARY_SUPPLEMENT

A single oral dose of 50 µg yohimbine, administered as 2 x 1 tablets of Yohimbinum hydrochloricum D4® will be administered as drinking solution with 240mL of water under overnight fasting conditions. A total of 6 blood samples will be collected at defined time points (baseline; 10; 20; 30; 60; 120 min). At each time point, 5 mL of blood will be drawn for plasma separation to determine yohimbine and the primary metabolite 11-OH-yohimbine.

Extensive Metabolizer (EM); Low Intermediate Metabolizer (LIM); Poor Metabolizers (PM):; Ultrarapid Metabolizer

Consumption of a defined potato-rich meal OTHER

Potato Intervention (2 phases): Diet restriction: No potato products 3 days before and until 60h after each meal. Ad libitum food intake is allowed from 6h post-meal. Blood will be analyzed for solanidine, its metabolites and its parent molecules α-solanine, and α-chaconine. Phase 1 (0-12h postprandial): Baseline blood draw at 8:00 AM, followed by supervised ingestion of a potato-rich meal. A total of 7 blood samples will be collected (baseline, 2, 4, 6, 8, 10, 12h) before discharge from the CRU. Phase 2 (12-60h postprandial): Baseline blood draw at 7:30 PM, identical meal ingestion at 8:00 PM. Participants can go home afterwards and return to the CRU the next morning at 8:00 AM for their 12 hour post meal blood draw. A total of 10 blood samples will be collected (baseline, 12, 14, 16, 18, 20, 22, 24h, 36h next morning, 60h subsequent morning).

Also known as: potato-rich meal, potato

Extensive Metabolizer (EM); Low Intermediate Metabolizer (LIM); Poor Metabolizers (PM):; Ultrarapid Metabolizer

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• individuals of both biological sexes, assigned as women or men at birth
• age: ≥ 18 and ≤ 40 years
• possesses the ability to understand the study purpose and design
• contractually capable and provides signed informed consent form
• in good general health or with mild and/or well-managed conditions such as allergies, asthma, hypertension or orthopedic diseases
• taking no more than three chronic medications
• ability to maintain and record a detailed dietary protocol focusing on the consumption of potato-based products for the specified duration of the study
• individuals classified as either ultrarapid metabolizers (UM), extensive metabolizers (EM), low intermediate metabolizers (LIM) or poor metabolizers (PM) based on their CYP2D6 genotype:
• Poor Metabolizer (PM, Gen-Score 0):
• homozygous or compound heterozygous for CYP2D6 \*3, CYP2D6 \*4, CYP2D6\*5, CYP2D6 \*6
• Low Intermediate Metabolizer (LIM, Gen-Score 0,25 or 0,5):
• Homozygous or compound heterozygous for CYP2D6 \*9, \*10, \*41 or compound heterozygous with one allele of CYP2D6 \*3, CYP2D6 \*4, CYP2D6\*5, or CYP2D6\*6 and one allele of CYP2D6 \*17 (0,5) or CYP2D6 \*9, \*10, or \*41 (0,25)
• Extensive Metabolizer (EM, Gene-Score 2):
• homozygous or compound heterozygous for CYP2D6 \*1, CYP2D6 \*2, CYP2D6\*35
• Ultrarapid Metabolizer (UM, Gen-Score ≥ 3):

You may not qualify if:

• BMI \> 30 kg/m2 and \< 18 kg/m2
• body weight \< 48 kg
• women: known pregnancy or lactation period; positive urine pregnancy test at screening or kinetic visit
• men: hemoglobin \< 13 g/dl (8,07 mmol/l) women: hemoglobin \< 12 g/dl (7,45 mmol/l)
• elevated liver function tests (1 or more of ALAT, ASAT, yGT, Bilirubin \> 2x ULN)
• reduced renal function (eGFRMDRD \< 60 mL/min/1,7 m2)
• QTcF \> 450 ms in screening ECG
• current or recent psychiatric disorders requiring treatment including depression, bipolar disorder, schizophrenia, psychosis or severe anxiety disorders
• drug dependency at the time of visit
• use of recreational drugs more than twice a week
• intake of drugs interfering with CYP2D6 during the past seven days
• any known hypersensitivity or allergic reactions to yohimbine
• intake of yohimbine within 48 hours prior to study participation
• history of hypersensitivity or allergy to potatoes or nightshade vegetables
• intake of potato-containing meals during the three days before and after eating the potato-rich test meal

Sponsors & Collaborators

• University Medicine Greifswald: lead

Study Sites (1)

University Medicine Greifswald

Greifswald, Mecklenburg-Vorpommern, 17489, Germany

Location

MeSH Terms

Interventions

Yohimbine

Intervention Hierarchy (Ancestors)

Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Central Study Contacts

Stefan Engeli, Prof. Dr.

CONTACT

+49 3834 86 5633; stefan.engeli@med.uni-greifswald.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study; no parties involved are masked.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med Stefan Engeli

Model Details: The study is designed as an open-label, controlled, parallel-cohort design with four study arms based on CYP2D6 genotype.

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: September 14, 2026
• Study Start: September 21, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)