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AOD Effects and ConsequencesNCT02515526

Effect of Acute Ethanol Consumption on The Activity of Major Cytochrome P450 Enzymes, NAT2 and P-glycoprotein

A study testing caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses and ethanol multiple doses plus caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses in people with AOD Effects and Consequences, run by University of Cologne at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Protocol title: Effect of acute alcohol consumption on the activity of major cytochrome P450 enzymes, NAT2 and P-glycoprotein. Objectives: The study is mainly conducted to evaluate the effect of acute alcohol consumption on the activity of the most important drug metabolising cytochrome P450 enzymes CYP1A2, CYP2C9… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
AOD Effects and Consequences
What is being tested?
caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses and ethanol multiple doses plus caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteGermany
Study dates
Jun 2015to 27 Aug 2015
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Caucasian
  • Age: 18-55 years
  • Normal body weight: (body mass index 18.5-30 kg/m2)
  • Considered to be healthy on the basis of extensive pre-study screening
  • Willing and capable to confirm written consent prior to enrolment after ample information has been provided.
  • Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant ("clinically healthy"). The inclusion criterion "clinically healthy" will be determined both by physical examination and clinical-chemical tests which will be done prior to the clinical part of the study

Who cannot join

  • subjects with any relevant clinical abnormality (as based on extensive medical history, physical examination, vital signs and 12-lead ECG)
  • subjects with electrolyte disturbances
  • subjects with any cardiac arrhythmia
  • subjects with a history or evidence of hypertrophic obstructive cardiomyopathy
  • subjects with a history or evidence of stenosis of the gastrointestinal tract
  • subjects a history or evidence of ulcerative colitis
Show all 31Show fewer
  • subjects a history or evidence of toxic mega colon
  • subjects with a history or evidence of myasthenia gravis
  • subjects with evidence of chronic infections
  • subjects with a history or evidence of bronchial asthma, COPD, pneumonia or other relevant respiratory diseases
  • subjects with acute infections within the last two weeks
  • subjects with a history of any allergic disease with clinical signs including hay fever and drug allergies
  • subjects with suspicion of hypersensitivity to the investigational medications and/or subjects with a history of severe skin reactions
  • subjects with any clinically relevant laboratory abnormality (incl. positive results for hepatitis and HIV serology)
  • subjects receiving any medication within 1 week prior to study start or during the study (exceptions possible upon decision of Principal Investigator, e.g. paracetamol single dose for acute pain or topical acyclovir for herpes labialis)
  • subjects who have taken a drug with a long half-life (> 24 hours) within four weeks before the first trial day
  • subjects who received chronic drug treatment (> 3 days) within eight weeks before the first trial day
  • subjects who participated in a trial with novel investigational medications within the last 8 weeks before the start of the present study
  • subjects who participated in a trial with a registered compound within the last 4 weeks before the start of the present study
  • subjects who donated blood or plasma within the last 4 weeks before the start of the present study
  • actual smokers defined as subjects who smoked any cigarette during the last three months
  • subjects who are known or suspected to be (social) drug dependent, incl. those drinking more than 50 g alcohol per day, those subjects must reduce their consumption to 30 g.
  • subjects with a history of alcohol or recreational drug addiction
  • subjects with positive drug screening tests
  • subjects with a history of any severe disease that might interfere with the study objectives
  • subjects who are not willing or able to abstain from alcohol, other than given as a study medication in the Reference period, methylxanthine-containing beverages and foods, caffeine containing products, papaver containing products and grapefruit flesh / juice starting from 72 hours before admission to the ward for the study until after the post screening tests
  • subjects who adhere to a special diet (e.g. vegetarians) or lifestyle (incl. working at night and extreme physical activities such as competitive sports and weight lifting) that might interfere with the investigation
  • subjects planning elective hospital treatment within one month after last intake of trial medication
  • subjects who are known or suspected not to comply with the study directives and/or known or suspected not to be reliable or trustworthy
  • subjects who are known or suspected not to be capable of understanding and evaluating the information that is given to them as part of the formal information policy (informed consent), in particular regarding the foreseeable risks and discomfort to which they will be exposed.
  • Anticipated problems of successfully placing an indwelling venous catheter at the forearms

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Department of Pharmacology I, University Hospital Cologne

    Cologne, North Rhine-Westphalia, 50931

Other trials in Germany

About this study

Protocol title: Effect of acute alcohol consumption on the activity of major cytochrome P450 enzymes, NAT2 and P-glycoprotein.

Objectives: The study is mainly conducted to evaluate the effect of acute alcohol consumption on the activity of the most important drug metabolising cytochrome P450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, intestinal CYP3A4, hepatic CYP3A4, NAT2 and on the activity of the drug transporter p-glycoprotein (intestinal and renal).

Read more

The study should also provide basis for a planned clinical study on interactions caused by chronic alcohol intake.

Design: Single center, open-label, two-way, cross-over study with randomly allocated sequences Test-Reference or Reference-Test.

The study is not a clinical drug study according to the German Drug Act.

Clinical phase: Not applicable

Volunteers: 16 healthy male and female subjects are planned for completion in accordance with the protocol, i.e. with evaluable/analysable data for all periods and treatments.

Clinical centre: Department of Pharmacology, Clinical Pharmacology Unit (KPH), University of Cologne, Gleueler Str. 24, 50931Köln, Germany

Being tested
caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses, ethanol multiple doses plus caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single dosesDrug

    Also called Percoffedrinol, Tolbutamide PCH, Omepazol Ratiopharm, Hustenstiller Ratiopharm, Digacin and Midazolam-ratiopharm

    Reference period

  • ethanol multiple doses plus caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single dosesDrug

    Also called Percoffedrinol, Tolbutamide PCH, Omepazol Ratiopharm, Hustenstiller Ratiopharm, Digacin, Midazolam-ratiopharm and Wodka Gorbatschow 50%

    Test period

Study groups in NCT02515526
Study groupRoleWhat they receive
ReferenceActive comparatorA cocktail of six different test substances to be administered orally followed by an I.V. dose of midzolam
Receives: Drug: caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses
TestExperimentalA cocktail of six different test substances to be administered orally followed by an I.V. dose of midzolam. In addition, ethanol will be administered at six different time points with of reaching a blood alcohol concentration of 1 per mille to see its effect on the activity of major cytochrome P450 enzymes, NAT-2 and P-glycoprotein.
Receives: Drug: ethanol multiple doses plus caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CYP1A2: AUC0-t of caffeine in plasma

    Measured: 2 months

  2. NAT2 activity: (AFMU + AAMU) / (AFMU + AAMU + 1X + 1U)

    Measured: 2 months

  3. CYP2C9: AUC0-t of tolbutamide in plasma

    Measured: 2 months

  4. CYP2C19: Molar omeprazole / 5-OH-omepazole AUC0-t ratio

    Measured: 2 months

  5. CYP2D6: Molar dextromethorphan / dextrorphan AUC0-t ratio

    Measured: 2 months

  6. Hepatic CYP3A4: hepatic clearance of midazolam

    Measured: 2 months

  7. Intestinal CYP3A4: intestinal extraction of midazolam

    Measured: 2 months

  8. Intestinal p-glycoprotein: absolute bioavailability of digoxin (calculated as Ae)

    Measured: 2 months

  9. Renal p-glycoprotein: renal secretion of digoxin

    Measured: 2 months

Secondary outcomes (7)

  1. CYP1A2: Molar paraxanthine /caffeine AUC0-t ratio

    Measured: 2 months

  2. CYP2C9: Tolbutamide plasma concentration 24 h post-dose

    Measured: 2 months

  3. CYP2C19: AUC0-t of omeprazole in plasma

    Measured: 2 months

  4. CYP2C19: Molar omeprazole / 5-OH-omepazole plasma concentration ratio

    Measured: 2 months

  5. CYP2D6: AUC0-t of dextromethorphan in plasma

    Measured: 2 months

  6. CYP2D6: Molar dextromethorphan / dextrorphan plasma concentration ratio

    Measured: 2 months

  7. Intestinal p-glycoprotein: digoxin Cmax

    Measured: 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2015 (estimated)
  2. Study startJun 2015
  3. Primary completion27 Aug 2015
  4. Study completion27 Aug 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02515526
Sponsor's protocol ID
EtOH_CYP_2013_KPUK
Status last verified
Sep 2019
First submitted
1 Aug 2015
Last updated
9 Sep 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Hsin CH, Stoffel MS, Gazzaz M, Schaeffeler E, Schwab M, Fuhr U, Taubert M. Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin. Sci Rep. 2020 Jul 27;10(1):12457. doi: 10.1038/s41598-020-69326-y.

    PubMed 32719417

Questions about this trial

What is this clinical trial studying?

A study testing caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses and ethanol multiple doses plus caffeine, tolbutamide, omeprazole, dextromethorphan, digoxin, midazolam single doses in people with AOD Effects and Consequences, run by University of Cologne at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CYP1A2: AUC0-t of caffeine in plasma (time frame: 2 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02515526, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2019.

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