Effects of Propranolol (vs. Placebo) on Information Processing During Presentation of Emotionally Arousing Pictures
- Conditions
- Emotions
- Interventions
- Drug: placeboDevice: Net Station® System and compatible Geodesic Sensor Nets®Device: VITAPORTDevice: ergoselect II 100/200Device: SpiroScoutDevice: Mobil-O-Graph® PWAProcedure: Saliva collection
- Registration Number
- NCT02509559
- Lead Sponsor
- University Medicine Greifswald
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 8
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18 - 35 years
-
male
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caucasian
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body mass index: > 19 kg/m² and < 27 kg/m²
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genotype:
- being homozygote for ADRB2 haplotype 2 (variant allele) and homozygote for ADRB1 c.1165 (CC)
- being homozygote for ADRB2 haplotype 2 (variant allele) and homozygote for ADRB1 c.1165 (GG) or heterozygote for ADRB1 c.1165 (CG)
- being homozygote for ADRB2 haplotype 4 (wild-type) and homozygote for ADRB1 c.1165 (CC)
- being homozygote for ADRB2 haplotype 4 (wild-type) and homozygote for ADRB1 c.1165 (GG) or heterozygote for ADRB1 c.1165 (CG)
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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)
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written informed consent
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo ergoselect II 100/200 Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule. Propanolol propranololhydrochloride Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. Propanolol VITAPORT Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. Propanolol Mobil-O-Graph® PWA Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. Propanolol Saliva collection Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. Placebo VITAPORT Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule. Placebo Saliva collection Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule. Propanolol Net Station® System and compatible Geodesic Sensor Nets® Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. Placebo Mobil-O-Graph® PWA Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule. Propanolol ergoselect II 100/200 Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. Placebo SpiroScout Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule. Propanolol SpiroScout Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. Placebo placebo Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule. Placebo Net Station® System and compatible Geodesic Sensor Nets® Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule.
- Primary Outcome Measures
Name Time Method hit rate 90 min after study medication number of correctly recognized learned pictures over number of all pictures
false alarm rate 90 min after study medication number of unlearned pictures incorrectly categorized as old over number of all pictures
dicrimination index 90 min after study medication hit rate minus false alarm rate
event-related potentials (ERPs given in µV) 90 min after study medication ERPs were extracted from the continuous electroencephalography signal (EEG). ERPs analyzed during encoding were late positive potentials (LPPs) in the time-range 550-1000 ms after stimulus onset. ERPs analyzed during recognition were late positive complexes (LPCs) for stimuli associated with hit responses (learned pictures correctly recognized as known) and correct rejections (unlearned pictures correctly categorized as unknown) in time range 550-700 ms after stimulus onset. Subtraction of amplitude values for both types of LPCs results in ERP old/new effects.
- Secondary Outcome Measures
Name Time Method heart rate 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 Forced Expiratory Volume in 1 second (FEV 1) up to 10 min before and 2 h after study medication Skin Conductance Response (SCR in the time-window up to 6.5 s after stimulus onset, in µmho) up to 10 min before and 90 min and 4 h after study medication The skin conductance will be measured between two electrodes attached to the participant's palm. SCRs will be averaged for every participant over following conditions: unpleasant, neutral and pleasant during encoding; and unpleasant old, neutral old, pleasant old, unpleasant new, neutral new, and pleasant new during recognition.
skin conductance level (SCL, in mikroSiemens over a time range of 120 s [µmho]) up to 10 min before and 90 min and 4 h after study medication The skin conductance will be measured between two electrodes attached to the participant's palm.
systolic blood pressure (mmHg) 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 diastolic blood pressure (mmHg) 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 mean arterial pressure (MAP) up to 10 min before and 20, 40, 60, 80, 120 min, 3, 5, 7, 11 h after study medication It is defined as the average arterial pressure during a single cardiac cycle.
α-amylase activity in saliva up to 1 min before and 80 min and 2 h after study medication concentration in U/ml
Trial Locations
- Locations (1)
Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald
🇩🇪Greifswald, Mecklenburg-Vorpommern, Germany