Effects of Propranolol (vs. Placebo) on Information Processing During Presentation of Emotionally Arousing Pictures

NCT02509559 | Completed Phase 1 DMC

• 1 other identifier: BBEmoMem_G
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Emotions

Keywords

Receptors, Adrenergic; Propranolol

Outcome Measures

Primary Outcomes (4)

• hit rate

  number of correctly recognized learned pictures over number of all pictures

  90 min after study medication

• false alarm rate

  number of unlearned pictures incorrectly categorized as old over number of all pictures

  90 min after study medication

• dicrimination index

  hit rate minus false alarm rate

  90 min after study medication

• event-related potentials (ERPs given in µV)

  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.

  90 min after study medication

Secondary Outcomes (8)

• 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

• 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

• 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

Other Outcomes (4)

• area under the concentration time curve (AUC) of propanolol

  before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication

• maximum concentration (Cmax) of the concentration time curve of propanolol

  before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication

• time point of maximum concentration (tmax) of the concentration time curve (AUC) of propanolol

  before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication

Study Arms (2)

Propanolol

ACTIVE COMPARATOR

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.

Drug: propranololhydrochloride; Device: Net Station® System and compatible Geodesic Sensor Nets®; Device: VITAPORT; Device: ergoselect II 100/200; Device: SpiroScout; Device: Mobil-O-Graph® PWA; Procedure: Saliva collection

Placebo

PLACEBO COMPARATOR

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.

Drug: placebo; Device: Net Station® System and compatible Geodesic Sensor Nets®; Device: VITAPORT; Device: ergoselect II 100/200; Device: SpiroScout; Device: Mobil-O-Graph® PWA; Procedure: Saliva collection

Interventions

propranololhydrochloride DRUG

oral administration of one capsule Propanolol-CT 80 mg Filmtabletten (propranololhydrochloride, film-coated tablet encapsulated, 80 mg, single dose) together with 240 ml tap water and blood sampling at time points blank, 15, 30, 45 min, 1, 2, 3, 4, 6, 8, 10, 12 h of study days 1 and 3 and urine sampling for 24 h at study days 1 and 3 with subsequent measuring of propranolol and its clinically relevant metabolites

Also known as: propanolol pharmacokinetics

Propanolol

placebo DRUG

oral administration of one placebo capsule together with 240 ml tap water and blood sampling at time points blank, 15, 30, 45 min, 1, 2, 3, 4, 6, 8, 10, 12 h of study days 1 and 3 and urine sampling for 24 h at study days 1 and 3

Also known as: placebo capsule

Placebo

Net Station® System and compatible Geodesic Sensor Nets® DEVICE

Electrocortical activity will be assessed by continuous EEG recording using Net Station® System and compatible Geodesic Sensor Nets® (Electrical Geodesics Incorporated, Eugene, OR, USA), measured at days 1, 3 and 10 of the study. Event related potentials at encoding (late positive potential, LPP) and at retrieval (ERP memory old/new effect) will be computed off-line after acquisition of the data.

Placebo; Propanolol

VITAPORT DEVICE

Measurement of the skin conductance by VITAPORT (Vitaport EDV Systeme GmbH, Erftstadt, Germany) on study days 1 and 3 at the time points before administration of the study medication, during the psychophysiological measurement and at 4 h. Furthermore, the skin conductance responses will be measured on day 10 during the psychophysiological measurement.

Placebo; Propanolol

ergoselect II 100/200 DEVICE

Performance of an ergometry by ergoselect II 100/200 (ergoline GmbH, Bitz, Germany) on study days 1 and 3 at 120 min. The burden will be the same wattage over 4 min, that corresponds to that of reaching 80% of the maximal heart frequency in the prestudy examination.

Placebo; Propanolol

SpiroScout DEVICE

Performance of a spirometry (SpiroScout, Ganshorn Medizin Electronic GmbH, Niederlauer, Germany) with measuring of the forced expiratory volume in 1 second (FEV1) on study days 1 and 3 before administration of the study medication and at 120 min.

Placebo; Propanolol

Mobil-O-Graph® PWA DEVICE

Measurement of pulse waves by Mobil-O-Graph® PWA (I.E.M., Stollberg, Germany) on study days 1 and 3 at the time points -10 min, 20, 40, 60, 80, 120 min, 3, 5, 7, 11 h.

Placebo; Propanolol

Saliva collection PROCEDURE

Saliva collection will be performed on study days 1 and 3 at time points -10 min, 80 min, 120 min with subsequent measuring of the concentration of α -amylase

Placebo; Propanolol

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years
• male
• caucasian
• body mass index: \> 19 kg/m² and \< 27 kg/m²
• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medicine Greifswald: lead

Study Sites (1)

Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald

Greifswald, Mecklenburg-Vorpommern, 17487, Germany

Location

Study Officials

• Werner Siegmund, Prof

  Department of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 28, 2015
• Study Start: October 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: January 1, 2015
• Last Updated: July 28, 2015

Record last verified: 2015-07

Locations

DE (1)