- To educate adolescents about clinical drug studies by involving them as project team members and participants in an experiment with negligible risk and minimal burden;- To investigate the effects of paracetamol on nociception in adolescents; - To…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
nociceptive pain (disorders)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Pharmacokinetics: saliva paracetamol concentrations
* Pharmacodynamics: pain threshold and tolerance levels for:
o heat pain (skin) (degrees Celsius),
o pressure pain (muscle) (kPa),
o electrical pain (skin) (mA),
o cold pressor pain (sec).
The results of the questionnaire on participation.
Secondary outcome
N/A.
Background summary
There is a wide discrepancy between the consumption of the drug among children
and adolescents and knowledge of its pharmacokinetic and pharmacodynamic
properties in these age groups. A greater understanding of how paracetamol
provides pain relief may lead to better analgesia as well as improved
utilization of analgesic polypharmacy in adolescents.
Study objective
- To educate adolescents about clinical drug studies by involving them as
project team members and participants in an experiment with negligible risk and
minimal burden;
- To investigate the effects of paracetamol on nociception in adolescents;
- To describe saliva paracetamol concentrations in adolescents;
- To describe the PK/PD relationship of paracetamol in adolescents (using data
obtained in the healthy adult volunteer study);
- To evaluate the applicability of the PainCart test battery in adolescents,
including evaluation how adolescents have experienced trial participation.
Study design
This will be a randomized, placebo-controlled, double-blind crossover study
with a wash-out period of at least one day between study days.
Intervention
(1) 1000 mg (2 capsules of 500 mg) paracetamol (2) placebo.
Study burden and risks
Paracetamol has few unwanted side effects. However, it is expected that these
will not occur at the dose that will be administered during the study (see
paragraph 5.4 and 5.6 of the protocol). The proposed tests are without risks
for the volunteer (e.g., do not cause tissue damage or psychological trauma).
Exclusion criteria addressing risk factors for fainting have been included. In
addition, participants will have unlimited access to fluids to ensure hydration
prior and during the experiments to reduce the risk of fainting due to
vasovagal stress responses. Also, participants will be given time to habituate
to the laboratory setting before starting the tests. Therefore, the risk
related to participating in this study is considered to be minimal.
The proposed tests generally cause some pain, but (1) the participant has
control over the process (i.e. control of cessation during the test); (2) the
pain mounts fairly slowly so that it can be terminated before it becomes
severe, and (3) the discomfort subsides rapidly once the test is terminated.
Also, the participant knows the maximum duration of the pain and that no harm
is being done, despite the fact that the test is painful. Based on our previous
experience with the pain tests in adult volunteers, it is anticipated that the
cold pressor test will be the relatively most demanding test in adolescents.
The pain induced by the cold pressor test is considered to be comparable to
experiences that can be encountered voluntary in everyday life (see paragraph
4.3.2 of the protocol). Subjects indicating nociceptive tests intolerable at
screening will be excluded. Measurement days will be planned on weekend days,
during holiday periods or on days that are considered to be suitable by the
parents, school and the adolescent to avoid school absence. At each measurement
day the participants will be requested to complete 5 measurement sessions
(including baseline session) of approximately 25 min. Time between sessions can
be spent with the other volunteers and/or parents in a room, where
entertainment like game consoles, DVD player and computers with internet access
is available. Staff experienced in working with adolescents will be present to
supervise and entertain the volunteers. Food and beverages will be provided at
regular intervals. The duration of study days is comparable to the duration of
a day in school.
Similar data-intensive studies with caffeine and alcohol in the same age group
were well tolerated and evaluated positively by all subjects (CHDR0918 and
CHDR1011, data on file). Therefore, based on previous experience, this study is
considered below the threshold of minimal burden.
The study objectives cannot be met by performing the study in legally competent
adults. Pharmacokinetic and pharmacodynamic properties of paracetamol may
change with age. Extent of placebo effect, psychological interpretation of pain
and maturation of pain pathways may affect the relationship between drug
concentration and pain relief, and may be different between children and
adults. In addition, pediatric subjects may typically differ from adult
participants on a number of variables that might influence pain test outcomes,
including biological variables as well as psychological variables. Please see
paragraph 4.3.3. for more details.
Zernikedreef 10
2333 CL Leiden
NL
Zernikedreef 10
2333 CL Leiden
NL
Listed location countries
Age
Inclusion criteria
* Agree to and be capable of signing an informed consent form.
* Written informed consent from parents having parental responsibility or from the legal guardian;
* Healthy male and female subjects;
* Age: 16 or 17 years at screening;
* Attending high school;
* Body mass index between 18-30 kg*m-2;
* Able to refrain from strenuous physical exercise from 48 hours prior to nociceptive testing until dismissal from the CHDR clinic;
* Able to refrain from alcohol use from 24 hours prior to and for the duration of every stay at the CHDR clinic;
* Ability to communicate well with the investigator in the Dutch language.
* Previous use of paracetamol without adverse effects
Exclusion criteria
* Inability to comply with the requirements of the study;
* Known liver and/or renal disease as determined by medical history taking;
* Clinically significant findings as determined by medical history taking
* Any current, clinically significant, known medical condition, in particular any existing conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud*s disease, urticaria, hypothyroidism) or pain (paraesthesia, etc.);
* Medical history of fainting or syncope e.c.i.;
* Previous allergic reaction to paracetamol;
* Pregnancy and/or breast feeding in females;
* Subjects indicating nociceptive tests intolerable at screening or achieving tolerance at >70% of maximum input intensity for any nociceptive test;
* Have a urine drug screen detecting illicit drug of abuse (morphine, benzodiazepines, cocaine, amphetamine, THC, methamphetamines, MDMA) or a positive alcohol breath test at screening;
* Consume, on average, >8 units/day of (methyl)xanthines (e.g. coffee, tea, cola, chocolate) and not able to refrain from use during each stay at the CHDR clinic;
* History or clinical evidence of alcoholism or drug abuse;
* Smoking of >5 cigarettes/day or equivalent and not able to abstain from smoking cigarettes during each stay at the CHDR clinic;
* Use of prescription, illicit or herbal medication within 7 days of nociceptive assessments;
* Use of over-the-counter analgesic medications within 3 days of nociceptive assessments.
* Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005086-20-NL |
| CCMO | NL38626.000.11 |