Does Propranolol Attenuate Inflammatory Responses to a Psychological Stressor?

NCT02972554 | Completed Phase 4 Results

• 1 other identifier: 16-2498
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stress, Psychological; Inflammation; Cortisol; Sympathetic Nervous System

Outcome Measures

Primary Outcomes (1)

• Change in Interleukin-6 (IL-6)

  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.

  Pre-drug baseline; 60-min post-drug administration baseline before stressor; 30-min post-stressor; 60-min post-stressor; 90-min post-stressor

Secondary Outcomes (5)

• Change in Salivary Cortisol

  Pre-drug baseline; 60-min post-drug administration baseline before stressor; 15-min post-stressor; 30-min post-stressor

• Change in Salivary Alpha Amylase

  Pre-drug baseline; 60-min post-drug administration baseline before stressor; 15-min post-stressor

• Change in Pre-Ejection Period

  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

• Change in Respiratory Sinus Arrhythmia

  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

• Change in Negative, High Arousal Emotion

  Pre-drug baseline; 60-min post-drug administration baseline before stressor; 2-min before the stressor; 1-min post-stressor

Study Arms (2)

Propanolol Hydrochloride

EXPERIMENTAL

This is the experimental group given the beta-blocker

Drug: Propanolol hydrochloride

Placebo

PLACEBO COMPARATOR

This is the control group given a placebo.

Other: Placebo

Interventions

Propanolol hydrochloride DRUG

One-time dose of 40mg of propranolol

Also known as: Inderal

Propanolol Hydrochloride

Placebo OTHER

Outside casing matching that of active drug

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

Inclusionary Criteria: 1. Healthy volunteers 2. Age 18-25 3. Fluent in English Exclusionary Criteria: 1. presence or history of chronic physical illness (especially disorders with an inflammatory component, such as rheumatoid arthritis, asthma, allergies, or issues that can affect the heart, including low-blood pressure or other heart conditions) 2. presence or history of psychiatric illness (depression, anxiety) 3. any current prescription medication use 4. currently pregnant or planning to become pregnant 5. engagement in a number of health--compromising behaviors that may affect levels of pro-inflammatory cytokines, including cigarette smoking, excessive caffeine intake and sleep disturbance (e.g., working night shifts) 6. body mass index (BMI) greater than 30, given that adiposity is known to relate to baseline levels of inflammation 7. anxiety about or previous history of problems with blood draws (e.g., fainting) 8. any reported heart conditions 9. history of fainting spells 10. low pulse, as measured at beginning of session I (below 60) 11. low blood pressure, as measured at beginning of session I (below 80)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

Howell Hall

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (32)

• Adler N, Stewart J. The MacArthur Scale of Subjective Social Status. 2007. http://www.macses.ucsf.edu.

  BACKGROUND

• Baker DG, Nievergelt CM, O'Connor DT. Biomarkers of PTSD: neuropeptides and immune signaling. Neuropharmacology. 2012 Feb;62(2):663-73. doi: 10.1016/j.neuropharm.2011.02.027. Epub 2011 Mar 22.

  PMID: 21392516 BACKGROUND

• Baron-Cohen S, Wheelwright S, Hill J, Raste Y, Plumb I. The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. J Child Psychol Psychiatry. 2001 Feb;42(2):241-51.

  PMID: 11280420 BACKGROUND

• Barrett LF. Feelings or words? Understanding the content in self-report ratings of experienced emotion. J Pers Soc Psychol. 2004 Aug;87(2):266-81. doi: 10.1037/0022-3514.87.2.266.

  PMID: 15301632 BACKGROUND

• Beck, A.T., Steer, R.A., & Brown, G.K. (1996). Manual for the Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation.

  BACKGROUND

• Benschop RJ, Nieuwenhuis EE, Tromp EA, Godaert GL, Ballieux RE, van Doornen LJ. Effects of beta-adrenergic blockade on immunologic and cardiovascular changes induced by mental stress. Circulation. 1994 Feb;89(2):762-9. doi: 10.1161/01.cir.89.2.762.

  PMID: 7508828 BACKGROUND

• Blascovich, J. & Mendes, W. B. (2000). Challenge and threat appraisals: The role of affective cues. In Forgas, J. (Ed.). Feeling and thinking: The role of affect in social cognition (pp. 59-82). New York, NY: Cambridge University Press.

  BACKGROUND

• Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert PM, Petrov D, Ferstl R, von Eynatten M, Wendt T, Rudofsky G, Joswig M, Morcos M, Schwaninger M, McEwen B, Kirschbaum C, Nawroth PP. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1920-5. doi: 10.1073/pnas.0438019100. Epub 2003 Feb 10.

  PMID: 12578963 BACKGROUND

• Capuron L, Miller AH. Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry. 2004 Dec 1;56(11):819-24. doi: 10.1016/j.biopsych.2004.02.009.

  PMID: 15576057 BACKGROUND

• Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001 Mar 22;344(12):907-16. doi: 10.1056/NEJM200103223441207. No abstract available.

  PMID: 11259725 BACKGROUND

• Cohen S, Janicki-Deverts D, Miller GE. Psychological stress and disease. JAMA. 2007 Oct 10;298(14):1685-7. doi: 10.1001/jama.298.14.1685. No abstract available.

  PMID: 17925521 BACKGROUND

• DellaGioia N, Hannestad J. A critical review of human endotoxin administration as an experimental paradigm of depression. Neurosci Biobehav Rev. 2010 Jan;34(1):130-43. doi: 10.1016/j.neubiorev.2009.07.014. Epub 2009 Aug 8.

  PMID: 19666048 BACKGROUND

• DeRijk RH, Boelen A, Tilders FJ, Berkenbosch F. Induction of plasma interleukin-6 by circulating adrenaline in the rat. Psychoneuroendocrinology. 1994;19(2):155-63. doi: 10.1016/0306-4530(94)90005-1.

  PMID: 8190835 BACKGROUND

• Kendler KS, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry. 1999 Jun;156(6):837-41. doi: 10.1176/ajp.156.6.837.

  PMID: 10360120 BACKGROUND

• Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, Atkinson C, Malarkey WB, Glaser R. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):9090-5. doi: 10.1073/pnas.1531903100. Epub 2003 Jul 2.

  PMID: 12840146 BACKGROUND

• Kirschbaum C, Pirke KM, Hellhammer DH. The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28(1-2):76-81. doi: 10.1159/000119004.

  PMID: 8255414 BACKGROUND

• Kleckner IR, Wormwood JB, Simmons WK, Barrett LF, Quigley KS. Methodological recommendations for a heartbeat detection-based measure of interoceptive sensitivity. Psychophysiology. 2015 Nov;52(11):1432-40. doi: 10.1111/psyp.12503. Epub 2015 Aug 12.

  PMID: 26265009 BACKGROUND

• Kop WJ, Weissman NJ, Zhu J, Bonsall RW, Doyle M, Stretch MR, Glaes SB, Krantz DS, Gottdiener JS, Tracy RP. Effects of acute mental stress and exercise on inflammatory markers in patients with coronary artery disease and healthy controls. Am J Cardiol. 2008 Mar 15;101(6):767-73. doi: 10.1016/j.amjcard.2007.11.006. Epub 2008 Feb 21.

  PMID: 18328837 BACKGROUND

• Miller G, Chen E, Cole SW. Health psychology: developing biologically plausible models linking the social world and physical health. Annu Rev Psychol. 2009;60:501-24. doi: 10.1146/annurev.psych.60.110707.163551.

  PMID: 19035829 BACKGROUND

• Nosek, B. A., Banaji, M., & Greenwald, A. G. (2002). Harvesting implicit group attitudes and beliefs from a demonstration web site. Group Dynamics: Theory, Research, and Practice, 6(1), 101-115.

  BACKGROUND

• Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002 Jan 15;51(2):189-92. doi: 10.1016/s0006-3223(01)01279-3.

  PMID: 11822998 BACKGROUND

• Raison CL, Miller AH. The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D). Mol Psychiatry. 2013 Jan;18(1):15-37. doi: 10.1038/mp.2012.2. Epub 2012 Jan 31.

  PMID: 22290120 BACKGROUND

• Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom Med. 2014 Apr;76(3):181-9. doi: 10.1097/PSY.0000000000000049.

  PMID: 24608036 BACKGROUND

• Steptoe A, Kivimaki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012 Apr 3;9(6):360-70. doi: 10.1038/nrcardio.2012.45.

  PMID: 22473079 BACKGROUND

• Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull. 2014 May;140(3):774-815. doi: 10.1037/a0035302. Epub 2014 Jan 13.

  PMID: 24417575 BACKGROUND

• Slavich GM, Way BM, Eisenberger NI, Taylor SE. Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14817-22. doi: 10.1073/pnas.1009164107. Epub 2010 Aug 2.

  PMID: 20679216 BACKGROUND

• Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun. 2007 Oct;21(7):901-12. doi: 10.1016/j.bbi.2007.03.011. Epub 2007 May 1.

  PMID: 17475444 BACKGROUND

• Emerging Risk Factors Collaboration; Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010 Jan 9;375(9709):132-40. doi: 10.1016/S0140-6736(09)61717-7. Epub 2009 Dec 22.

  PMID: 20031199 BACKGROUND

• Vaiva G, Ducrocq F, Jezequel K, Averland B, Lestavel P, Brunet A, Marmar CR. Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry. 2003 Nov 1;54(9):947-9. doi: 10.1016/s0006-3223(03)00412-8.

  PMID: 14573324 BACKGROUND

• van Gool J, van Vugt H, Helle M, Aarden LA. The relation among stress, adrenalin, interleukin 6 and acute phase proteins in the rat. Clin Immunol Immunopathol. 1990 Nov;57(2):200-10. doi: 10.1016/0090-1229(90)90034-n.

  PMID: 1698583 BACKGROUND

• Wittenbrink B, Judd CM, Park B. Evidence for racial prejudice at the implicit level and its relationship with questionnaire measures. J Pers Soc Psychol. 1997 Feb;72(2):262-74. doi: 10.1037//0022-3514.72.2.262.

  PMID: 9107001 BACKGROUND

• MacCormack JK, Armstrong-Carter EL, Gaudier-Diaz MM, Meltzer-Brody S, Sloan EK, Lindquist KA, Muscatell KA. beta-Adrenergic Contributions to Emotion and Physiology During an Acute Psychosocial Stressor. Psychosom Med. 2021 Nov-Dec 01;83(9):959-968. doi: 10.1097/PSY.0000000000001009.

  PMID: 34747583 DERIVED

MeSH Terms

Conditions

Stress, Psychological; Inflammation

Interventions

Propranolol; Sugars

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Carbohydrates

Limitations and Caveats

1\. Not all salivary alpha amylase samples were assayed in duplicate because there was not enough saliva for the 15-min post-stress time point. 2. For the first ten subjects, a shorter version of the PANAS with 20 rather than full 40 items was used.

Results Point of Contact

• Title: Dr. Keely A. Muscatell
• Organization: University of North Carolina at Chapel Hill

kmuscatell@unc.edu

919-843-9113

Study Officials

• Keely A Muscatell, Ph.D

  University of North Carolina at Chapel Hill, Psychology & Neuroscience

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: November 23, 2016
• Study Start: January 26, 2016
• Primary Completion: October 10, 2017
• Study Completion: October 10, 2017
• Last Updated: December 19, 2018
• Results First Posted: December 19, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)