NCT02972554

Does Propranolol Attenuate Inflammatory Responses to a Psychological Stressor?

Completed Phase 4 Results posted Last updated 19 December 2018

What this trial tests

Phase 4 trial testing Propanolol hydrochloride in Stress, Psychological in 92 participants. Completed in 10 October 2017.

Timeline

26 January 2016

Primary endpoint
10 October 2017

10 October 2017

Quick facts

Lead sponsor	University of North Carolina, Chapel Hill
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	basic science
Enrollment	92
Start date	26 January 2016
Primary completion	10 October 2017
Estimated completion	10 October 2017
Sites	1 location across United States

Drugs / interventions tested

• Propanolol hydrochloride
• Placebo

Conditions studied

• Stress, Psychological — all drugs for Stress, Psychological →
• Inflammation — all drugs for Inflammation →
• Cortisol — all drugs for Cortisol →
• Sympathetic Nervous System — all drugs for Sympathetic Nervous System →

Sponsor

University of North Carolina, Chapel Hill

Who can join

Adults 18 to 25, any sex, with Stress, Psychological or Inflammation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Interleukin-6 (IL-6) Primary · Pre-drug baseline; 60-min post-drug administration baseline before stressor; 30-min post-stressor; 60-min post-stressor; 90-min post-stressor

Measured in blood plasma using enzyme-linked immunosorbent assay. Log-transformed prior to analysis to correct for skew in data. Four different change scores were calculated: first, change at post-drug from pre-drug baseline; second, the change at 30-min post-stressor from post-drug baseline; third, change at 60-min post-stressor from post-drug baseline; and fourth, change at 90-min post-stressor from post-drug baseline.

Post-drug from pre-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.05	-.126 – .226
Placebo	.16	-.075 – .395

30-min post-stress from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.31	.016 – .604
Placebo	.24	.044 – .436

60-min post-stress from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.32	.006 – .634
Placebo	.19	.014 – .366

90-min post-stress from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.48	.206 – .754
Placebo	.46	.264 – .656

Change in Salivary Cortisol Secondary · Pre-drug baseline; 60-min post-drug administration baseline before stressor; 15-min post-stressor; 30-min post-stressor

Concentration of cortisol in saliva quantified quantified by chemiluminescence immunoassay with high sensitivity. Three different change scores were calculated from pre-drug to post-drug baselines, 15-min post-stressor from post-drug baseline, and 30-min post-stressor from post-drug baseline.

Post-drug from pre-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	-6.42	-8.576 – -4.264
Placebo	-3.76	-5.524 – -1.996

15-min post-stress from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	5.61	3.258 – 7.962
Placebo	4.02	2.785 – 5.255

30-min post-stress from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	2.1	.179 – 4.021
Placebo	1.86	.978 – 2.742

Change in Salivary Alpha Amylase Secondary · Pre-drug baseline; 60-min post-drug administration baseline before stressor; 15-min post-stressor

Concentration of alpha amylase in saliva quantified quantified by enzyme kinetic method. Two different change scores were calculated: first, the pre-drug to post-drug baseline change and, second, the 15-min post-stressor change from post-drug baseline.

Post-drug from pre-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	-7.50	-19.299 – 4.299
Placebo	-6.36	-16.787 – 4.067

15-min post-stress from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	-15.68	-26.725 – -4.635
Placebo	6.73	-3.305 – 16.765

Change in Pre-Ejection Period Secondary · Pre-drug baseline; 60-min post-drug administration baseline before stressor; 2-min before the stressor; 15-min during stressor, 7-min recovery post-stressor

Mean level pre-ejection period (PEP; centered at zero) derived from impedance cardiography and electrocardiogram. Four different change scores were calculated: first, the change in average PEP from the 5-min pre-drug baseline to the 5-min post-drug baselines; second, the change in average PEP that occurred during the 2-min anticipatory stress speech preparation phase of the Trier Social Stress Test (TSST) from the post-drug baseline; third, the change in average PEP that occurred across the 15-min of the TSST (speech + math tasks) from the post-drug baseline; fourth and finally, the change in

Post-drug from pre-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	7.14	1.711 – 12.569
Placebo	.86	-3.148 – 4.868

TSST-prep from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	-5.33	-9.828 – -.832
Placebo	-10.92	-14.859 – -6.980

TSST from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	-.80	-6.259 – 4.659
Placebo	-10.69	-14.816 – -6.564

Post-stress recovery from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.21	-4.063 – 4.483
Placebo	-1.19	-5.120 – 2.740

Change in Respiratory Sinus Arrhythmia Secondary · Pre-drug baseline; 60-min post-drug administration baseline before stressor; 2-min before the stressor; 15-min during stressor, 7-min recovery post-stressor

Mean level respiratory sinus arrhythmia (RSA) derived from electrocardiogram; measure of heart rate variability assessed as the ratio of low-to-high frequencies in the respiratory-cardiac power spectrum. Four different change scores were calculated: first, the change in average RSA from the 5-min pre-drug baseline to the 5-min post-drug baselines; second, the change in average RSA that occurred during the 2-min anticipatory stress speech preparation phase of the Trier Social Stress Test (TSST) from the post-drug baseline; third, the change in average RSA that occurred across the 15-min of the

Post-drug from pre-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.11	-.173 – .395
Placebo	.27	-.025 – .563

TSST-prep from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.36	.076 – .644
Placebo	-.43	-.734 – -.126

TSST from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	-.06	-.332 – .212
Placebo	-.87	-1.20 – -.540

Post-stress recovery from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.36	.088 – .632
Placebo	-.26	-.593 – .073

Change in Negative, High Arousal Emotion Secondary · Pre-drug baseline; 60-min post-drug administration baseline before stressor; 2-min before the stressor; 1-min post-stressor

Self-report measure of affect (emotion) state using the Positive \& Negative Affect Schedule Negative Affect (PANAS). Answered on a Likert scale from 0 ("not at all") - 6 ("very much"). Mean score range is from 0-6. Higher numbers indicate more negative, high arousal emotions; low numbers indicate less negative, high arousal emotions. Three change scores were calculated from the four different rating measurement time points: a change in negative, high arousal emotions at the post-drug baseline from the pre-drug baseline; a change in emotions right before the Trier Social Stress Task (TSST) fro

Post-drug from pre-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	-.10	-.141 – -.059
Placebo	-.13	-.185 – -.075

TSST-prep from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.18	.122 – .238
Placebo	.37	.300 – .440

TSST stressor from post-drug baseline

Group	Value	95% CI
Propanolol Hydrochloride	.61	.532 – .689
Placebo	.76	.678 – .842

Sponsor's own description

This randomized, double-blind, placebo-controlled study of propranolol will shed important light on how sympathetic nervous system (SNS) activation influences psychological and inflammatory responses to acute stress. Results from this study will inform both the basic science literature that is attempting to map the physiological mechanisms by which psychological stress may lead to poor mental and physical health, and may also ultimately have therapeutic relevance for individuals who are experiencing high levels of stress that is putting their health at risk. Utilizing a psychopharmacological approach allows for the circumvention of many of the challenges of conducting this research in human populations, and will allow for conclusions regarding causality, given that SNS activation will be experimentally manipulated, rather than relying on correlational measures of SNS activity that are difficult to assess and are not appropriate for asking if SNS activity causes changes in psychology and biology.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Beta-adrenergic blockade blunts inflammatory and antiviral/antibody gene expression responses to acute psychosocial stress.
   MacCormack JK, Gaudier-Diaz MM, Armstrong-Carter EL, Arevalo JMG, et al · · 2021 · cited 29× · PMID 33452438 · DOI 10.1038/s41386-020-00897-0
2. β-Adrenergic Contributions to Emotion and Physiology During an Acute Psychosocial Stressor.
   MacCormack JK, Armstrong-Carter EL, Gaudier-Diaz MM, Meltzer-Brody S, et al · · 2021 · cited 19× · PMID 34747583 · DOI 10.1097/psy.0000000000001009