Experimental study with healthy participants recruited from the general population
Conditions
Interventions
Trade Name: Propranolol EG (Eurogenerics NV) - 40 mg
Product Name: Propranolol
Product Code: C07AA05
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of
Sponsors
UZ Leuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age: In principle, there are not limitations with respect of age, but to prevent excessive heterogeneity we will recruit adult participants between 18 and 40 years of age. - Sex: We will include both men and women. Healthy participants (N = 60) ranging in the age of 18 to 40 will take part in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participation in this study is contingent on participants not meeting a number of exclusion criteria: Some of those exclusion criteria are tied to the nature of the behavioral tasks that will be used (i.e., fear-conditioning) and have been determined in agreement with the KU Leuven Social and Societal Ethics Committee (SMEC). As such, we exclude pregnant woman, people with cardiovascular conditions, lung problems, neurologic conditions (e.g., epilepsy, seizures, convulsions), serious psychiatric conditions (depression, mania, psychosis, anxiety disorder) in the past or the present, or other serious medical conditions, people with pace-makers or other electronic implants, people with (uncorrected) hearing impairments and people with pain, injury or other medical conditions at the hands or wrists. Similarly excludes are people who have been advised by their physician to keep away from stressful situations. Specific exclusion criteria also apply for the administration of propranolol. Those include a history of low blood pressure, dizziness, or fainting, inability to perform moderate exercise, cardiac problems in first-degree relative, a history of diabetes, liver or kidney problems, metabolic acidosis, excessive production of thyroid hormone, circulatory problems, current use of medication that acts on the cardiac system, antihypertensive drugs, migraine medication, blood sugar level depression medication, gastric acid blinding drugs, anti-inflammatory agents, antidepressants, antipsychotics, anxiolytics, asthma medication, drugs against dizziness, migraine, tuberculosis, or psoriasis, known allergy for propranolol, current systolic blood pressure below 90 or diastolic blood pressure below 60, current heart rate at rest below 60 or heart rate immediately after two-step exercise test equal to or below heart rate at rest. We also exclude all participants with a score on the Anxiety Sensitivity Index above 25.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The effect of drug state on memory retrieval after induced experimental amnesia using Propranolol EG 40 mg. Our objective is to test wether the internal drug state induced by a single dose of propranolol (40 mg) is salient/potent enough to make retrieval of a conditioned fear memory reactivated before drug administration state-dependent.;Secondary Objective: Replication of earlier demonstrations of experimental amnesia after administration of a single dose of propranolol during fear memory reconsolidation (Kindt et al., 2009). ;Primary end point(s): Our primary endpoint is to test whether the adminstration of propranolol on both day 2 (directly after reactivation of a fear memory) and day 3 (prior to extinction testing and reinstatement; i.e., the Propranolol-Propranolol group) recovers the conditioned fear responses (in fear potentiated startle) on day 3 relative to a group that receives propranolol on day 2 after reactivation of the CS+ but placebo on day 3 (Propranolol-Placebo group). For the latter group, we expect similar findings as Kindt and colleagues (2009), namely an absence of CS+/CS-/NA differentiation at the beginning of day 3 testing in fear-potentiated startle responses. A third (control) group that receives placebo on days 2 and 3 is included (Placebo-Placebo group) to ascertain that the lack of differential startle responding on day 3 in the Propranolol-Placebo is drug-specific. If the assumption is true that propranolol-induced amnesia is due to propranolol inducing an internal drug state which gets integrated within the initial memory trace, we should not see significant differences between the Placebo-Placebo group and the Propropranolol-Propranolol group in startle responding on day 3. We do not expect any differences between the conditions in US-expectancy ratings (in line with Kindt et al., 2009). ;Timepoint(s) of evaluation of this end point: Three day protocol with a final evaluation test on day 3. Placebo/propranolol is adm | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Our second aim is to replicate the original study of Kindt et al. (2009), who showed that fear responses can be permanently weakened by administration of propranolol upon memory reactivation, preventing later return of fear. We will therefore include a fourth condition with no fear reminder trial on day 2 before the administration of propranolol. This group will receive placebo on day 3. We expect that this group will not show an attenuation of the differential startle response on day 3, since previous research with propranolol has indicated that reactivation of the fear memory is crucial to induce experimental amnesia (i.e., attenuation of the fear-potentiated startle response on a delayed retrieval test). ;Timepoint(s) of evaluation of this end point: Day 3 or final test day. | — |
Countries
Belgium
Contacts
Public ContactPI Tom Beckers
KU Leuven
Outcome results
None listed