Clinical trial NCT02509559: Effects of Propranolol (vs. Placebo) on Information Processing During Presentation of Emotionally Arousing Pictures
Official title: Effects of Propranolol (vs. Placebo) on Information Processing During Presentation of Emotionally Arousing Pictures After Single Dose (80 mg) Administration and Relationships Between ß1- and ß2-adrenoreceptors Genotype and Both the Information Processing and the Propranolol Effects in 64 Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Emotions
Keywords: Receptors, Adrenergic
Propranolol
Lead sponsor: University Medicine Greifswald
Sponsor class: OTHER
First posted: 2015-07-28
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The main objective of the present study is to combine two lines of research, investigating the interaction between emotional processing and memory performance (on both behavioral and electrophysiological levels) and its modulation by ß-blockade.

Concerning pharmacological manipulations with ß-blockers, there are no studies, which investigated the effects of propranolol on electrophysiological (ERPs) and behavioral measures of recognition memory along with their codependence on individual variations of adrenergic receptors' polymorphisms. Till now, also the findings about genetic influences of ADRB1 and ADRB2 on recognition memory for emotional contents are lacking.

Therefore, the current investigation has been designed to replicate the former results which revealed reduced ERP correlates of recognition memory for emotional pictures due to administration of ß-blocker propranolol. Furthermore investigators goal is to test, whether there are any differences between carriers of genetic variants of the ADRB1 and ADRB2 in memory performance and/or changes in event-related potentials and in propranolol influences on the above mentioned processes.

In conclusion, investigators hypothesize: (1) a memory advantage of emotionally arousing stimuli over emotionally neutral pictures; (2) more pronounced ERP components (EPN, LPP, old-new effect) associated with encoding and memory for emotional stimuli; (3) a reduction of electrocortical correlates of emotional recognition memory (old-new effect) caused by propranolol; (4) a potential impact of genetic variants of the ADRB1 and ADRB2 on the emotional information processing and memory formation alone, and on the propranolol modulation of those processes.

Furthermore, investigators hypothesize additional pharmacodynamic effects of propranolol such as influence on skin- conductance, pulse waves, burdening heart frequency, pulmonary function and metabolomics, which might depend on the ADRB1 and ADRB2 genotype.


Eligibility criteria: Inclusion Criteria:

* 18 - 35 years
* male
* caucasian
* body mass index: \> 19 kg/m² and \< 27 kg/m²
* genotype:

  1. being homozygote for ADRB2 haplotype 2 (variant allele) and homozygote for ADRB1 c.1165 (CC)
  2. being homozygote for ADRB2 haplotype 2 (variant allele) and homozygote for ADRB1 c.1165 (GG) or heterozygote for ADRB1 c.1165 (CG)
  3. being homozygote for ADRB2 haplotype 4 (wild-type) and homozygote for ADRB1 c.1165 (CC)
  4. being homozygote for ADRB2 haplotype 4 (wild-type) and homozygote for ADRB1 c.1165 (GG) or heterozygote for ADRB1 c.1165 (CG)
* good health as evidenced by the results of the clinical examination, ECG, ergometry and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state; the lower limit for systolic pressure is stated with 110 mm Hg and diastolic blood pressure with 70 mmHg as well as heart frequency should not fall below 50 bpm (WHO definition)
* written informed consent

Exclusion Criteria:

* sex: female
* hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication
* existing cardiac or hematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability and/or pharmacokinetics (e.g. bradycardia, hypotonia, av- block I°)
* volunteers liable to orthostatic dysregulation, fainting, or blackouts
* peripheral circulatory disturbances
* gastrointestinal diseases and/or pathological findings (e.g. stenoses), which might interfere with pharmacokinetics and pharmacodynamics of the study medication
* obstructive disorder of breathing (e. g. asthma bronchiale)
* known allergic reactions to the active ingredients used or to constituents of the study medication
* known allergic reactions to any drug therapy in the anamnesis or actual de-allergisation
* psoriasis
* diabetes mellitus
* addiction to hypoglycemia
* pheochromocytoma
* myasthenia gravis
* drug or alcohol dependence
* positive drug or alcohol screening
* smokers of 10 or more cigarettes per day
* positive results in HIV, HBV and HCV screenings
* volunteers who are on a diet which could affect the pharmacokinetics of the drug (e. g. vegetarian
* heavy tea or coffee drinkers (more than 1L per day)
* volunteers suspected or known not to follow instructions of the clinical investigators
* volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
* less than 14 days after last acute disease
* any medication within 4 weeks prior to the intended first administration of the study medication which might influence functions of the gastrointestinal tract (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists, proton pump inhibitors, anticholinergics)
* any other medication within two weeks prior to the first administration of the study medication, but at least 10-time the half-live of the respective drug (except oral contraceptives)
* intake of grapefruit containing food or beverages within 14 days prior to administration of the study medication
* intake of poppy seed containing food or beverages within 14 days prior to administration of the study medication

Primary outcomes:
measure: hit rate
timeFrame: 90 min after study medication
measure: false alarm rate
timeFrame: 90 min after study medication
measure: dicrimination index
timeFrame: 90 min after study medication
measure: event-related potentials (ERPs given in µV)
timeFrame: 90 min after study medication
Secondary outcomes:
measure: Forced Expiratory Volume in 1 second (FEV 1)
timeFrame: up to 10 min before and 2 h after study medication
measure: Skin Conductance Response (SCR in the time-window up to 6.5 s after stimulus onset, in µmho)
timeFrame: up to 10 min before and 90 min and 4 h after study medication
measure: heart rate
timeFrame: up to 1 min before and 20, 40, 60, 80 min, 2, 3, 5, 7 and 11 h after study medication and during ergometry (0-2 min and 2-4 min) 2 h after study medication
measure: systolic blood pressure (mmHg)
timeFrame: up to 1 min before and 20, 40, 60, 80 min, 2, 3, 5, 7 and 11 h after study medication and during ergometry (0-2 min and 2-4 min) 2 h after study medication
measure: diastolic blood pressure (mmHg)
timeFrame: up to 1 min before and 20, 40, 60, 80 min, 2, 3, 5, 7 and 11 h after study medication and during ergometry (0-2 min and 2-4 min) 2 h after study medication
measure: α-amylase activity in saliva
timeFrame: up to 1 min before and 80 min and 2 h after study medication
measure: skin conductance level (SCL, in mikroSiemens over a time range of 120 s [µmho])
timeFrame: up to 10 min before and 90 min and 4 h after study medication
measure: mean arterial pressure (MAP)
timeFrame: up to 10 min before and 20, 40, 60, 80, 120 min, 3, 5, 7, 11 h after study medication
Other outcomes:
measure: area under the concentration time curve (AUC) of propanolol
timeFrame: before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication
measure: maximum concentration (Cmax) of the concentration time curve of propanolol
timeFrame: before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication
measure: time point of maximum concentration (tmax) of the concentration time curve (AUC) of propanolol
timeFrame: before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication
measure: terminal half life (t1/2) of the concentration time curve of propanolol
timeFrame: before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication
Locations:
city: Greifswald
country: Germany
facility: Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald
state: Mecklenburg-Vorpommern
Study officials:
affiliation: Department of Clinical Pharmacology
name: Werner Siegmund, Prof
role: PRINCIPAL_INVESTIGATOR
References: