We will examine the cognitive performance of healthy young participants at different time points after a single administration of biperiden. The behavioural outcomes and electrophysiological correlates will be linked with the serum levels of…
ID
Source
Brief title
Condition
- Other condition
- Cognitive and attention disorders and disturbances
Synonym
Health condition
aandachtstekorten
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
the main endpoints for the cognitive tasks are the behavioural scores on the
immediate and delayed recall of the VLT. This includes the number of words
recalled immediately and after a 20-minute delay.
Amendment:
The main endpoints for the attention tasks are the behavioral score on
Alerting, Orienting and Executive Network (ANT), endogenous and exogenous
attention (VCT), and recognition of deep encoded, shallowly encoded and novel
stimuli (BUNM).
Secondary outcome
To establish the pharmacokinetic and pharmacodynamic profile of biperiden, the
primary endpoints will be the blood serum values and physiological measures
(body temperature, blood pressure, heart rate and pupil size). Furthermore the
behavioural outcomes of the n-back, DAT, and simple and choice reaction tasks
will be used for analysis, as well as the score on the B&L and complaints
questionnaire. Next to this, the event-related potentials during the
behavioural tasks will be analysed. Another important measure is the brain
response to the novelty oddball task, which will give an indication of the role
of acetylcholine in novelty processing.
Amendment:
We will analyze the scores on general attention (VCT) the B&L and complaints
questionnaire. Next to this, the event-related potentials during the
behavioural tasks will be analyzed.
Background summary
Since current treatments for Alzheimer*s Disease are only show minimal effects,
it is of vital importance to search for drugs that are more successful. A way
to investigate possible drug therapies in young adults is to use
pharmacological deficit models to induce memory impairments that can mimic age-
and dementia-related memory impairments. The *golden standard* scopolamine is
known to cause side-effects (e.g., attention) that indirectly affect the
cognitive performance of participants. Therefore a more selective drug with
less peripheral side effects may be more preferable. Biperiden is a muscarinic
antagonist that, when administered to healthy subjects, produces memory
impairments without impairing attention or motor functions. So far, little
research was done to investigate the pharmacokinetics and - dynamics of
biperiden. In the current study, we will examine the pharmacokinetic and
pharmacodynamic profile of biperiden.
Amendment:
During an interim analysis of the current study, we found that the effects on
memory were much larger after 4 mg than after 2 mg. To exclude mediating
effects of attention to the memory impairment, we will only provide the 4 mg
dose to healthy volunteers and measure their attention. This is not necessary
for the 2 mg dose, as we did not find any significant effects on attention in a
previous study examining a 2 mg dose.
Study objective
We will examine the cognitive performance of healthy young participants at
different time points after a single administration of biperiden. The
behavioural outcomes and electrophysiological correlates will be linked with
the serum levels of biperiden to establish the pharmacodynamic and kinetic
properties. This will provide a better understanding of the time dependent
effects on physiological, brain activity, and cognitive functions in relation
to plasma levels. This is essential to characterize biperiden as a possible
pharmacological model for cognitive dysfunction in Alzheimer's Disease.
Amendment:
In this study, we examine cognitive performance on attention tasks. in the same
participants at one timepoint after biperiden administration. This is essential
to determine if biperiden is a good deficit-model for memory impairment, or
whether it impairs attention at higher doses and thus is not an appropriate
memory model.
Study design
The study will be conducted according to a double-blind, placebo controlled,
three-way cross-over design.
Amendment:
The study will be conducted according to a double-blind, placebo controlled,
two-way cross-over design.
Intervention
Subjects will participate in 3 treatment conditions: i.e. placebo and biperiden
2 mg and biperiden 4 mg. All medications will be administered orally. Order of
treatments will be balanced over three test sessions, which will be separated
by a washout period of at least 7 days.
Amendment:
Subjects will participate in 2 treatment conditions: i.e. placebo and biperiden
2 mg. All medications will be administered orally. Order of treatments will be
balanced over two test sessions, which will be separated by a washout period of
at least 7 days.
Study burden and risks
The time investment for the participants will be around 29 hours (or 1740 min),
which is comprised of 1) medical screening (60 min), 2) training session of
cognitive tasks (60 min), and 3) three test sessions of around 540 min. The day
before each test day, the participants are not allowed to drink any alcohol.
During each test session multiple blood samples bill be taken. The treatment
are single doses of biperiden 2.0 mg or 4.0 mg, and placebo.
Amendment:
The time investment for the participants will be around 8 hours (480 minutes),
which is comprised of 1) medical screening (60 min), 2) training session of
cognitive tasks (60 min), and 3) two test sessions of around 180 min. The day
before each test day, the participants are not allowed to drink any alcohol.
The treatments are single doses of biperiden 2.0 mg and placebo.
Universiteitssingel 40
Maastricht 6229 ER
NL
Universiteitssingel 40
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant has a body mass index of 18.5-30 kg/m2, inclusive, at medical screening.
• The participant is aged 18 to 35 years, inclusive, at the time of informed consent.
• The volunteer is healthy, i.e. absence of all exclusion criteria and had normal or corrected to normal static binocular acuity with or without correction.
• The participant signs and dates a written informed consent form before the start of the experiments.
• The participant has sufficient knowledge of the English language.
Exclusion criteria
• The subject has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may impact the ability of the subject to participate or potentially confound the study results.
• The volunteer has uncontrolled existing major psychiatric symptoms.
• The participant has known hypersensitivity to any component of the formulation or biperiden or related compounds.
• The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the first visit or is unwilling to agree to abstain from alcohol from 24 hours prior to each test day and/or drugs throughout the study.
• The participant has any sensory or motor deficits which could reasonably be expected to affect test performance.
• Other exclusion criteria are smoking, excessive drinking (>20 glasses of alcohol containing beverages a week), pregnancy or lactation, use of medication other than oral contraceptives.
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 | EUCTR2016-003357-14-NL |
| CCMO | NL58970.068.16 |