Condition category
Not Applicable
Date applied
10/06/2019
Date assigned
11/06/2019
Last edited
11/06/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Chemicals known as furanocoumarins (8-methoxypsoralen [8-MOP] and 5-methoxypsoralen [5-MOP]) are known to inhibit the breakdown (metabolism) of caffeine. However, it is not known if ingestion of herbs containing these chemicals will have the same effect. The aim of this study is to determine if a single meal of furanocoumarin-containing herb (or vegetable) would cause inhibition of caffeine metabolism after co-administration.

Who can participate?
Healthy volunteers aged 20 - 35 years (non-smoker, not pregnant or breastfeeding).

What does the study involve?
Collection of timed saliva and urine samples from you after ingesting caffeine tablets (200 mg) alone and caffeine tablets (200 mg) with an herb (or vegetable) together (total caffeine consumption by you is 400 mg for the whole study).

What are the possible benefits and risks of participating?
BENEFITS:
You will not benefit directly from this study. No information or results obtained by this study will be made available to you. However, there is the potential to benefit other people in the future if the study leads to the development of an effective method for predicting caffeine/herb interaction using in vitro data.
RISKS:
There will be no risk to your health because the amount of caffeine ingested is equivalent that in a cup of coffee. Moreover, the herbs (or foods) selected for the study are found in our daily diets. Please note that caffeine overdose only occurs when large amount of caffeine (more than the recommended dose by Health Canada) is ingested. Caffeine overdose may result in adverse health effects including nausea, vomiting, irritability, nervousness, anxiety, panic attacks, dehydration, and sleep disorders in sensitive individuals (Health Canada, 2012).

Where is the study run from?
Department of Biological Sciences, Simon Fraser University, BC, Canada

When is the study starting and how long is it expected to run for?
June 2012 to June 2016

Who is funding the study?
1. Simon Fraser University, Canada
2. Global Collaborative Research, King Abdullah University of Science and Technology

Who is the main contact?
Dr Zeyad Alehaideb
alehaidebze1@ngha.med.sa

Trial website

Contact information

Type

Scientific

Primary contact

Dr Zeyad Alehaideb

ORCID ID

http://orcid.org/0000-0002-7185-2820

Contact details

3690
Al Yasmin
Riyadh
13325 8348
Riyadh
11111
Saudi Arabia
0566188111
alehaidebze1@ngha.med.sa

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

KAIMRC ZE-001

Study information

Scientific title

Caffeine/Angelica dahurica and caffeine/Salvia miltiorrhiza metabolic inhibition in humans: In vitro and in vivo studies.

Acronym

Study hypothesis

Caffeine metabolism (CYP1A2-Mediated) can be modulated by pre-consumption of two Chinese medicines of Danshen (Salvia miltiorrhiza) and Baizhi (Angelica dahurica).

Ethics approval

Approved 20/09/2012, Simon Fraser University Office of Research Ethics Committee (Discovery 2 building, 8900 Nelson Way, Burnaby BC V5A 4W9; +1 778-782-6593dore@sfu.ca), ref: 2012s0565

Study design

Interventional (cross-over) single center

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Home

Trial type

Prevention

Patient information sheet

See additional files

Condition

N/A

Intervention

Participants are asked to refrain from ingesting caffeine, caffeinated drinks and furanocoumarin-containing foods for 3 days before and after participating in the first pharmacokinetic study (without co-treatment with an herb) and until the end of the second pharmacokinetic study (with co-treatment of an herb). Participants are provided with a study kit consisting of caffeine tablets (400 mg), an herbal extract, and several coded containers for saliva and urine sample collection. Participants conduct the studies in the home:
First pharmacokinetic study:
Time course of caffeine and metabolite concentrations in the saliva of humans without herb/food extract co-treatment. On the day of the experiment, ingest 200 mg caffeine tablets (equivalent to the amount of caffeine in a cup of coffee or in a can of energy drink). A saliva sample (about 3 ml) will be collected in a coded, siliconized glass tube just before dosing. Serial saliva samples also will be collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8 and 12 hr post-dosing. A 30 ml urine sample will be collected at 4-8 hr post caffeine administration since the half-life of caffeine clearance in the human is about 4-4.5 hr.
Second pharmacokinetic study:
Time course of caffeine and metabolite concentrations in the saliva of humans co-treated with an herb/food extract. After a 3-day wash-out period, ingest 4.5 g (or 9 g) of a dehydrated herb (or food) in the form of an aqueous extract 3 hr before ingesting the caffeine tablets. One of the following herbs or vegetables: parsnip, celery, dill, parsley, angelica, false bishop’s weed, common rue, lovage, khella, dong quai, and baizhi. A saliva sample (about 3 ml) will be collected in a coded, siliconized glass tube just before dosing. Serial saliva samples also will be collected immediately after dosing with an herb extract at 0.5, 1, 1.5, 2.5, 3.0 hr and after dosing with 200 mg caffeine at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8 and 12 hr. 30 ml urine samples will be collected before dosing and at 4-8 hr post-caffeine ingestion.

Intervention type

Drug

Phase

Not Applicable

Drug names

Caffeine; herbal whole aqueous extract of either Danshen (Salvia miltiorrhiza) and Baizhi (Angelica dahurica).

Primary outcome measure

Caffeine concentrations in human saliva collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8 and 12 hr post-dosing using liquid chromatography

Secondary outcome measures

Caffeine concentrations in urine collected 4 - 8 hours post-dosing

Overall trial start date

26/06/2011

Overall trial end date

29/06/2017

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Aged 20-35 years

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

8

Participant exclusion criteria

1. Smoker
2. On medication
3. Pregnant or breast feeding
3. Any health issue(s) that would affect the results of the study

Recruitment start date

20/06/2012

Recruitment end date

01/06/2016

Locations

Countries of recruitment

Canada

Trial participating centre

Simon Fraser University
Department of Biological Sciences Simon Fraser University
Burnaby
V5AIS6
Canada

Sponsor information

Organisation

Department of Biological Sciences, Simon Fraser University

Sponsor details

Burnaby
B.C. Canada V5A 1S6
Burnaby
V5A 1S6
Canada
+966566188111
zehaideb@gmail.com

Sponsor type

University/education

Website

http://www.sfu.ca

Organisation

King Abdullah International Medical Research center

Sponsor details

Department of Medical Genomics
King Abdullah International Medical Research Center
P.O. Box 3660
Riyadh
11111
Saudi Arabia
+966566188111
zehaideb@gmail.com

Sponsor type

Research organisation

Website

http://www.kaimec.med.sa

Funders

Funder type

University/education

Funder name

Simon Fraser University

Alternative name(s)

SFU

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Canada

Funder name

Global Collaborative Research, King Abdullah University of Science and Technology

Alternative name(s)

GCR, KAUST

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Saudi Arabia

Results and Publications

Publication and dissemination plan

To be published in thesis and journals.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made available due to the raw data not being available.

Intention to publish date

01/07/2019

Participant level data

Available on request

Basic results (scientific)

A. dahurica and S. miltiorrhiza extracts were capable of inhibiting caffeine metabolism in human subjects. In a separate study, cytochrome (CYP) 1A2-mediated caffeine demethylase activity was studied in incubation containing human liver microsomes, β-nicotinamide adenine dinucleotide phosphate, and an herbal extract (or a pure bioactive chemical from the herbs). In all cases, CYP1A2 activity was decreased with an increasing inhibitor concentration, confirming the inhibition of caffeine metabolism in vivo. Caffeine metabolism inhibition most likely involved the competitive and/or non-competitive mechanism.

Publication list

Publication citations

Additional files

Editorial Notes

11/06/2019: The participant information sheet has been uploaded.