Dose-dependent effects of propranolol on extinction learning and return of fear

Dose-dependent effects of propranolol on extinction learning and return of fear - WipeOutFear_Extinction

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-003409-25-BE

Enrollment

144

Registered

2018-10-02

Start date

2018-11-08

Completion date

Unknown

Last updated

2021-11-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Experimental study with healthy participants recruited from the general population

Interventions

Trade Name: Propranolol EG (Eurogenerics NV) - 40 mg Product Name: Propranolol Product Code: C07AA05 Pharmaceutical Form: Tablet INN or Proposed INN: PROPRANOLOL HYDROCHLORIDE CAS Number: 318-98-9 Con

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Healthy participants 18-40 years old. 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 144 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: We will exclude pregnant women, 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, people with pain, injury or other medical conditions at the hands or wrists, and 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. We will also exclude all participants with a score of 26 or above on the Anxiety Sensitivity Index (questionnaire).

Design outcomes

Primary

Measure	Time frame
Main Objective: In our previous study (2016-002392-10; S59302), we found evidence that 40 mg oral administration of Propranolol HCl 60 min prior to extinction training attenuates fear responding and facilitates extinction. Propranolol administration did not prevent the return of fear, however, we did not test for return of fear in absence of the drug. The main aim of the present study is to investigate whether propranolol has a dose-dependent effect on extinction learning, and whether this further prevents the return of fear, in absence of the drug. ;Secondary Objective: Our secondary objective is to investigate how the effective connectivity between neural regions-of-interest changes during fear extinction, and the dose-dependent effect of propranolol on these connections.;Timepoint(s) of evaluation of this end point: Three day protocol with an evaluation of the extinction learning on day 2 and a final evaluation test (for return of fear) on day 3. Placebo/propranolol will be administered on day 2.;Primary end point(s): Our primary endpoint (study part A) is to test whether the administration of propranolol prior to extinction attenuates the conditioned fear responses [fear-potentiated startle (FPS) and skin conductance (SCR)] during extinction (relative to a group that receives placebo prior to extinction), and subsequently prevents the return of fear (i.e., spontaneous recovery and reinstatement) the next day (in absence of the drug). In our previous study (2016-002392-10; S59302), we found an attenuation of FPS CS+/CS- responding (effect significantly stronger for CS+ responding) during extinction in a group that received 40 mg propranolol 60 min prior to extinction. We did not find any effects on reinstatement, yet, we tested for reinstatement while the drug was still active. We predict a similar CS+/CS- attenuation during extinction for the groups that receive propranolol, but we expect to observe a stronger decline in conditioned responding in the group that	—

Measure

Time frame

Main Objective: In our previous study (2016-002392-10; S59302), we found evidence that 40 mg oral administration of Propranolol HCl 60 min prior to extinction training attenuates fear responding and facilitates extinction. Propranolol administration did not prevent the return of fear, however, we did not test for return of fear in absence of the drug. The main aim of the present study is to investigate whether propranolol has a dose-dependent effect on extinction learning, and whether this further prevents the return of fear, in absence of the drug. ;Secondary Objective: Our secondary objective is to investigate how the effective connectivity between neural regions-of-interest changes during fear extinction, and the dose-dependent effect of propranolol on these connections.;Timepoint(s) of evaluation of this end point: Three day protocol with an evaluation of the extinction learning on day 2 and a final evaluation test (for return of fear) on day 3. Placebo/propranolol will be administered on day 2.;Primary end point(s): Our primary endpoint (study part A) is to test whether the administration of propranolol prior to extinction attenuates the conditioned fear responses [fear-potentiated startle (FPS) and skin conductance (SCR)] during extinction (relative to a group that receives placebo prior to extinction), and subsequently prevents the return of fear (i.e., spontaneous recovery and reinstatement) the next day (in absence of the drug). In our previous study (2016-002392-10; S59302), we found an attenuation of FPS CS+/CS- responding (effect significantly stronger for CS+ responding) during extinction in a group that received 40 mg propranolol 60 min prior to extinction. We did not find any effects on reinstatement, yet, we tested for reinstatement while the drug was still active. We predict a similar CS+/CS- attenuation during extinction for the groups that receive propranolol, but we expect to observe a stronger decline in conditioned responding in the group that

—

Secondary

Measure	Time frame
Secondary end point(s): In study Part B, we aim to replicate the findings for US-expectancy and SCR of study Part A in a second sample. Due to practical constraints FPS will not be measured. We will use Dynamic Causal Modelling (DCM) to quantify the directed influence between two anatomically defined regions-of-interest, specifically the vmPFC and amygdala. We expect that the vmPFC will have a greater influence over the activity in the amygdala during extinction and return of fear, than acquisition. We will then compare whether the strength of the influence from the vmPFC to the amygdala is related to the strength of propranolol administration.;Timepoint(s) of evaluation of this end point: Three day protocol with an evaluation of the extinction learning on day 2 and a final evaluation test (for return of fear) on day 3. Placebo/propranolol will be administered on day 2.	—

Measure

Time frame

Secondary end point(s): In study Part B, we aim to replicate the findings for US-expectancy and SCR of study Part A in a second sample. Due to practical constraints FPS will not be measured. We will use Dynamic Causal Modelling (DCM) to quantify the directed influence between two anatomically defined regions-of-interest, specifically the vmPFC and amygdala. We expect that the vmPFC will have a greater influence over the activity in the amygdala during extinction and return of fear, than acquisition. We will then compare whether the strength of the influence from the vmPFC to the amygdala is related to the strength of propranolol administration.;Timepoint(s) of evaluation of this end point: Three day protocol with an evaluation of the extinction learning on day 2 and a final evaluation test (for return of fear) on day 3. Placebo/propranolol will be administered on day 2.

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Countries

Belgium

Contacts

Public ContactPI Tom Beckers

KU Leuven

tom.beckers@kuleuven.be+32016326134

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026