Health TrialsbyHealthPanel

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

ConditionPharmacokinetic Study in Healthy Volunteers
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-40
SponsorUniversity Medicine Greifswald

About this trial

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. To evaluate the suitability of the SSDA/solanidine and m414/solanidine metabolic ratio as an exogenous biomarker to phenotype CYP2D6 activity in humans. 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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • Consumption of a defined potato-rich meal

    Other intervention

    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).

Treatment groups

30 Participants
are divided into 4 treatment groups
Group A: Poor Metabolizers (PM):Active comparator 2 interventions
Group B: Low Intermediate Metabolizer (LIM)Active comparator 2 interventions
Group C: Extensive Metabolizer (EM)Active comparator 2 interventions
Group D: Ultrarapid MetabolizerActive comparator 2 interventions

Trial outcomes

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)

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

Secondary outcomes

1

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

Plasma concentrations expressed as area under the curve (AUC) will be determined for solanidine, its CYP2D6-dependent metabolites SSDA and m414, and its parent molecules α-solanine and α-chaconine for each metabolizer status cohort (PM, LIM, EM, UM).

Time frame
60 hours
2

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

The maximum concentration (Cmax) will be determined for solanidine, its CYP2D6-dependent metabolites SSDA and m414, and its parent molecules α-solanine and α-chaconine for each metabolizer status cohort (PM, LIM, EM, UM).

Time frame
60 hours
3

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

Time to maximum concentration (tmax) of solanidine, its CYP2D6-dependent metabolites SSDA and m414, and its parent molecules α-solanine and α-chaconine will be determined for each metabolizer status cohort (PM, LIM, EM, UM).

Time frame
60 hours

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Medicine Greifswald

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: