Evaluation of Solanidine as an Exogenous Biomarker to Phenotype CYP2D6 Activity in Humans (SOLA-1)
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:
- To evaluate the suitability of the SSDA/solanidine and m414/solanidine metabolic ratio as an exogenous biomarker to phenotype CYP2D6 activity in humans.
- 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.
調査の概要
状態
詳細な説明
The study follows an open-label, controlled, parallel-cohort design with four study arms based on CYP2D6 genotype. The study consists of two parts: a Yohimbine and a Potato Part.
Yohimbine Part:
Participants will receive a single oral microdose of 50 μg of yohimbine, administered in a fasted state as 2 x 1 tablets of Yohimbinum hydrochloricum D4® (Deutsche Homöopathie Union, Karlsruhe, Germany, containing 25 μg per tablet). 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. The blood sampling protocol is based on the findings of the YOKI-1 study (protocol number: IPHA-2025-011, Greifswald Ethics Committee Registration number BB 069/25). At baseline, an additional blood sample will be collected for a random determination of solanidine and its metabolites. During the 2.5-hour stay in the CRU, participants will be asked to stay in bed.
Potato Part:
Between the Potato and the Yohimbine Part, a period of 4 weeks in any order is acceptable. The Potato Part is divided into two sequential phases: Phase 1 and Phase 2, both featuring supervised meal ingestion at the clincal research unit. During the three days before each Potato Phase and up to 60 hours afterward, no potato products should be eaten. Otherwise, ad libitum food intake is permitted beginning six hours after the potato-rich meal. Blood samples will be analyzed for solanidine, its CYP2D6-dependent metabolites, and its parent molecules α-solanine and α-chaconine in both Potato Phases. Both Potato Phases must be separated by at least one week.
Phase 1 (0-12 hours postprandial):
An initial baseline blood sample will be collected prior to the ingestion of the potato-rich meal. Participants will receive the potato-rich meal at 8 a.m., and a total of 7 blood samples will be collected at defined time points (baseline, 2, 4, 6, 8, 10, and 12 h).Upon successful completion of the 12-hour blood draw, participants will be discharged from the CRU.
Phase 2 (12-60 hours postprandial):
On a separate scheduled study day, participants will report to the CRU at 7:30 p.m. A baseline blood sample will be collected prior to meal ingestion. Participants will then ingest an identical, defined potato-rich meal at 8:00 p.m. Following meal consumption, participants are permitted to go home for the night. The next morning, starting at 7:30 a.m., blood sampling collections will begin at the designated time points. A total of ten blood samples will be collected at defined time points (baseline, 12, 14, 16, 18, 20, 22, 24 h, 36 h in the next morning and at 60 h in the morning thereafter).
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Stefan Engeli, Prof. Dr.
- 電話番号：+49 3834 86 5633
- メール：stefan.engeli@med.uni-greifswald.de
研究場所
-
-
Mecklenburg-Vorpommern
-
Greifswald、Mecklenburg-Vorpommern、ドイツ、17489
- University Medicine Greifswald
-
コンタクト：
- Stefan Engeli, Prof. Dr.
- 電話番号：+49 3834 86 5633
- メール：stefan.engeli@med.uni-greifswald.de
-
主任研究者：
- Stefan Engeli, Prof. Dr.
-
-
参加基準
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 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):
homozygous or compound heterozygous for CYP2D6 *1, CYP2D6 *2, CYP2D6*35 with at least one allele duplicated or multiplied
Exclusion Criteria:
- 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
- history of severe hypersensitivity reactions and/or anaphylaxis
- poor venous conditions that make it impossible to place a peripheral venous catheter and regularly draw blood through it
- engagement in extreme physical activity within 48 hours prior to study participation
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：Poor Metabolizers (PM):
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.
|
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.
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).
他の名前：
|
|
アクティブコンパレータ：Low Intermediate Metabolizer (LIM)
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.
|
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.
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).
他の名前：
|
|
アクティブコンパレータ：Extensive Metabolizer (EM)
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.
|
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.
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).
他の名前：
|
|
アクティブコンパレータ：Ultrarapid Metabolizer
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.
|
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.
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).
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Metabolic ratio of SSDA/solanidine
時間枠：From enrollment to 60 hours after eating the potato-rich meal.
|
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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
AUC for solanidine, SSDA, m414, α-solanine and α-chaconine
時間枠：60 hours
|
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).
|
60 hours
|
|
Cmax for solanidine, SSDA, m414, α-solanine and α-chaconine
時間枠：60 hours
|
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).
|
60 hours
|
|
Tmax for solanidine, SSDA, m414, α-solanine and α-chaconine
時間枠：60 hours
|
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).
|
60 hours
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- IPHA-2026-12
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。