Study of the Effects of Negative Emotions on Endothelial Function (PUME)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Columbia University
Sponsor:
Information provided by (Responsible Party):
Daichi Shimbo, Columbia University
ClinicalTrials.gov Identifier:
NCT01909895
First received: July 25, 2013
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

The experience of negative emotions is associated with an increased risk of incident atherosclerosis-related cardiovascular disease (CVD) events, independent of traditional risk factors. The strongest data supporting this relation is with provoked anger. There is also some evidence that becoming acutely depressed or anxious are also triggers of incident CVD. The underlying putative mechanisms are poorly understood. Vascular endothelial cells (ECs) play an essential role in maintaining vascular tone and the integrity of blood vessels. Evidence suggests that dysfunction of the endothelium is an early pathogenic process underlying atherosclerosis development and CVD event onset. The aims of this study are to primarily examine the acute effects of provoked anger and secondarily depressed mood and anxiety on EC health. Examination of these critical pathways will help determine whether endothelial dysfunction is a biological mechanism linking the experience of core negative emotions and incident CVD risk. In this application, a state-of-the-art, laboratory-based, randomized controlled experiment is proposed that will test whether provoked anger, depressed mood and anxiety will induce endothelial dysfunction in humans. We hypothesize that compared to an emotionally neutral condition, an anger recall task will impair endothelium-dependent vasodilation, injure ECs, and reduce EC reparative capacity. We will also examine whether a depressed mood and anxiety induction task will similarly induce endothelial dysfunction, as well as whether levels of provoked self-reported anger, depressed mood, and anxiety are associated with the degree of endothelial dysfunction. Finally, given that endogenous nitric oxide (NO) inhibition plays a central role in exacerbating endothelial dysfunction, we will explore whether NO inhibition partially mediates the acute adverse effects of provoked anger, depressed mood, and anxiety on endothelial function. In the United States, atherosclerosis-related CVD events remain the leading cause of morbidity and mortality. Further, anger, depressed mood, and anxiety are negative emotions commonly experienced by adults in the general population on a day-to-day basis. Therefore, evaluation of these hypotheses is timely and highly significant, as it will help identify a putative biological pathway linking the experience of core negative emotions to CVD incidence, for a large number of individuals who are at increased risk for CVD events.


Condition Intervention
Emotions
Endothelial Dysfunction
Other: Anger Induction
Other: Depressed Mood Induction
Other: Anxiety Induction
Other: Neutral emotion task

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Official Title: Translational Research of Negative Emotions and Acute Endothelial Dysfunction

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Endothelium-dependent arterial vasodilation [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 3 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 40 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 70 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 3 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 40 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 70 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 3 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 40 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 70 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 100 mins after end of mood induction ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Circulating EMPs expressing CD31 [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD51 [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Self-reported anger, depressed mood, and anxiety [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Nitric oxide(NO) inhibition [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]
    Circulating measures of asymmetric dimethylarginine (ADMA) and oxidative stress measures

  • Stress response [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]
    Circulating measures of catecholamines, cortisol, endothelin-1; blood pressure and heart rate


Estimated Enrollment: 280
Study Start Date: August 2013
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anger induction
The participant will be asked to undergo a validated anger induction task.
Other: Anger Induction
The participant will be asked to undergo a validated anger induction task.
Experimental: Depressed Mood Induction
The participant will be asked to undergo a validated depression/sadness induction task.
Other: Depressed Mood Induction
The participant will be asked to undergo a validated depression/sadness induction task.
Experimental: Anxiety Induction
The participant will be asked to undergo a validated anxiety induction task.
Other: Anxiety Induction
The participant will be asked to undergo a validated anxiety induction task.
Neutral emotion task
The participant will be asked to undergo a validated neutral task (i.e. count aloud by ones, starting with one and ending with 100, over and over, until the task period has ended).
Other: Neutral emotion task
This is a neutral control task that each of the negation emotion induction tasks will be compared to.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 and over
  • Fluent in English

Exclusion Criteria:

  • History of any chronic medical condition including prevalent CVD and traditional risk factors
  • Active smoking
  • Chronic medication use, including over-the-counter drugs or herbal medications
  • History of psychosis, a mood disorder, or any overt personality disorder
  • Latex allergy
  • Poor peripheral veins with low possibility of getting IV access
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01909895

Contacts
Contact: Daichi Shimbo, MD 212-342-4490 ds2231@columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Principal Investigator: Daichi Shimbo, MD         
Sub-Investigator: Matthew Burg, PhD         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Daichi Shimbo, MD Columbia University
  More Information

No publications provided

Responsible Party: Daichi Shimbo, Associate Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01909895     History of Changes
Other Study ID Numbers: AAAK4250
Study First Received: July 25, 2013
Last Updated: February 27, 2014
Health Authority: United States: Institutional Review Board

ClinicalTrials.gov processed this record on August 20, 2014