EmotionsPUMENCT01909895
Study of the Effects of Negative Emotions on Endothelial Function
A study testing Anger Induction, Depressed Mood Induction and Anxiety Induction in people with Emotions and Endothelial Dysfunction, run by Columbia University at 1 site in United States.
Trial summary
Study aims and hypotheses are as follows: Primary Hypotheses: Compared to the neutral condition, the anger recall task will acutely induce endothelial dysfunction by impairing endothelium-dependent arterial vasodilation (Hypothesis 1a); increasing circulating levels of EC-derived microparticles (EMPs), a marker of EC… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Emotions, Endothelial Dysfunction
- What is being tested?
- Anger Induction, Depressed Mood Induction and Anxiety Induction
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2013to 1 Nov 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 and over
- Fluent in English
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Translational Research of Negative Emotions and Acute Endothelial Dysfunction
Study aims and hypotheses are as follows:
Primary Hypotheses:
Read more
Compared to the neutral condition, the anger recall task will acutely induce endothelial dysfunction by impairing endothelium-dependent arterial vasodilation (Hypothesis 1a); increasing circulating levels of EC-derived microparticles (EMPs), a marker of EC injury (Hypothesis 1b); and reducing circulating levels of bone marrow-derived endothelial progenitor cells (EPCs), a marker of EC reparative capacity (Hypothesis 1c).
Secondary Hypotheses:
Compared to the neutral condition, the depressed mood and separately the anxiety recall tasks will acutely impair endothelium-dependent arterial vasodilation, increase circulating levels of EMPs, and reduce circulating levels of bone marrow-derived EPCs. There will be a relation of the level of self-reported anger, depressed mood, and anxiety with endothelial dysfunction.
Read the detailed description
Atherosclerosis-related cardiovascular disease (CVD) events remain the leading causes of morbidity and mortality in industrialized nations. Atherosclerosis is a diffuse disease characterized by the deposition of lipid and other blood-borne material within the arterial wall. Evidence demonstrates that disruption of an arterial atherosclerotic plaque and subsequent thrombus formation is responsible for the onset of CVD events. Cardiovascular research efforts have been directed toward the identification of early underlying factors that initiate this cascade.
It has been known for some time that the experience of negative emotions is associated with an increased risk of incident CVD events, independent of traditional risk factors. Among the best-studied negative emotions is anger. Population-based studies have demonstrated that the experience of anger is a trigger of incident CVD events. The mechanism(s) by which provoked anger acutely affects the pathways that underlie atherosclerosis development and progression remain to be fully characterized.
Endothelial dysfunction is a promising mechanism that may explain the link between anger and incident CVD events. Vascular endothelial cells (ECs) play essential roles in maintaining vascular tone and the integrity of blood vessels. Evidence suggests that endothelial dysfunction is an early pathogenic process underlying atherosclerosis development and CVD event onset. Our preliminary findings show in apparently healthy individuals, an anger recall task acutely induces endothelial dysfunction by impairing endothelium-dependent vasodilation, injuring ECs, and disrupting the molecular processes underlying EC reparative capacity. We have additionally found that this task may induce endogenous nitric oxide (NO) inhibition, which plays a central role in aggravating endothelial dysfunction. Therefore, NO inhibition may partially mediate anger-provoked endothelial dysfunction.
Although the strongest data are on anger-provoked CVD events, there is also some evidence that the experience of other core negative emotions such as depressed mood and anxiety may trigger CVD events. Whether the provocation of depressed mood and anxiety acutely induces endothelial dysfunction and NO inhibition remains to be determined. The overall aim of this study is to primarily examine the acute effects of provoked anger and secondarily depressed mood and anxiety on EC health. We will also explore whether NO inhibition partially mediates the acute effects of anger, depressed mood, and anxiety on endothelial function. Examination of these critical pathways will help identify the biological pathways by which the experience of core negative emotions leads to incident CVD risk.
To address these highly significant research questions, we propose a state-of-the-art, laboratory-based, randomized controlled experiment in which 280 participants will be randomized to one of four experimental conditions: an anger recall task (N=70), a depressed mood recall task (N=70), an anxiety recall task (N=70), and an emotionally neutral condition (N=70).
- Conditions
- Emotions, Endothelial Dysfunction
- Being tested
- Anger Induction, Depressed Mood Induction, Anxiety Induction, Neutral emotion task
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anger InductionOther
The participant is asked to recall an incident in the recent past during which they became moderately to extremely angry, or is asked to read statements out loud evoking moderate to extreme feelings of anger. The participant is asked to take a few moments to bring the details of the incident to mind and, when ready, to describe the incident in great detail to the experimenter. Participants are asked to describe key elements, such as any dialogue that transpired during the incident, along with other details of the incident, particularly regarding the feelings of that particular emotion experienced at the time. In so doing, the experimenter works to re-elicit the emotions that accompanied the original incident. The duration of the negative emotion induction task is 8 minutes.
Depressed Mood InductionOther
The participant will be asked to undergo a validated depression/sadness induction task.
Anxiety InductionOther
The participant will be asked to undergo a validated anxiety induction task.
Neutral emotion taskOther
This is a neutral control task that each of the negation emotion induction tasks will be compared to.
| Study group | Role | What they receive |
|---|---|---|
| Anger induction | Experimental | The participant will be asked to undergo a validated anger induction task. Receives: Other: Anger Induction |
| Depressed Mood Induction | Experimental | The participant will be asked to undergo a validated depression/sadness induction task. Receives: Other: Depressed Mood Induction |
| Anxiety Induction | Experimental | The participant will be asked to undergo a validated anxiety induction task. Receives: Other: Anxiety Induction |
| Neutral emotion task | Other | 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). Receives: Other: Neutral emotion task |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelium-dependent arterial vasodilation
Measured: baseline
Circulating EMPs expressing CD62E
Measured: baseline
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Measured: baseline
Endothelium-dependent arterial vasodilation
Measured: 3 mins after end of mood induction
Endothelium-dependent arterial vasodilation
Measured: 40 mins after end of mood induction
Endothelium-dependent arterial vasodilation
Measured: 70 mins after end of mood induction
Endothelium-dependent arterial vasodilation
Measured: 100 mins after end of mood induction
Circulating EMPs expressing CD62E
Measured: 3 mins after end of mood induction
Circulating EMPs expressing CD62E
Measured: 40 mins after end of mood induction
Circulating EMPs expressing CD62E
Measured: 70 mins after end of mood induction
Circulating EMPs expressing CD62E
Measured: 100 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Measured: 3 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Measured: 40 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Measured: 70 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Measured: 100 mins after end of mood induction
Secondary outcomes (3)
Circulating EMPs expressing CD31
Measured: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction
Circulating EMPs expressing CD51
Measured: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction
Self-reported anger, depressed mood, and anxiety
Measured: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2013 (estimated)
- Study start1 Sep 2013
- Primary completion1 Nov 2020
- Study completion1 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EmotionsStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Daichi Shimbo, Columbia University
- Investigators
- Daichi Shimbo, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01909895
- Sponsor's protocol ID
- AAAK4250
- Other IDs
- 1R01HL116470-01
- Acronym
- PUME
- Status last verified
- Jan 2022
- First submitted
- 25 Jul 2013
- Last updated
- 27 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ensari I, Burg MM, Diaz KM, Fu J, Duran AT, Suls JM, Sumner JA, Monane R, Julian JE, Zhao S, Chaplin WF, Shimbo D. Putative mechanisms Underlying Myocardial infarction onset and Emotions (PUME): a randomised controlled study protocol. BMJ Open. 2018 May 31;8(5):e020525. doi: 10.1136/bmjopen-2017-020525.
PubMed 29858417
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Translational Research of Negative Emotions and Acute Endothelial Dysfunction
- ClinicalTrials.gov ID
- NCT01909895
- Acronym / sponsor ID
- PUME / AAAK4250
- Conditions
- Emotions, Endothelial Dysfunction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 Sep 2013 (actual)
- Primary completion
- 1 Nov 2020 (actual)
- Study completion
- 1 Nov 2020 (actual)
- First posted
- 29 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study aims and hypotheses are as follows:
Primary Hypotheses:
Compared to the neutral condition, the anger recall task will acutely induce endothelial dysfunction by impairing endothelium-dependent arterial vasodilation (Hypothesis 1a); increasing circulating levels of EC-derived microparticles (EMPs), a marker of EC injury (Hypothesis 1b); and reducing circulating levels of bone marrow-derived endothelial progenitor cells (EPCs), a marker of EC reparative capacity (Hypothesis 1c).
Secondary Hypotheses:
Compared to the neutral condition, the depressed mood and separately the anxiety recall tasks will acutely impair endothelium-dependent arterial vasodilation, increase circulating levels of EMPs, and reduce circulating levels of bone marrow-derived EPCs. There will be a relation of the level of self-reported anger, depressed mood, and anxiety with endothelial dysfunction.
Detailed description
Atherosclerosis-related cardiovascular disease (CVD) events remain the leading causes of morbidity and mortality in industrialized nations. Atherosclerosis is a diffuse disease characterized by the deposition of lipid and other blood-borne material within the arterial wall. Evidence demonstrates that disruption of an arterial atherosclerotic plaque and subsequent thrombus formation is responsible for the onset of CVD events. Cardiovascular research efforts have been directed toward the identification of early underlying factors that initiate this cascade.
It has been known for some time that the experience of negative emotions is associated with an increased risk of incident CVD events, independent of traditional risk factors. Among the best-studied negative emotions is anger. Population-based studies have demonstrated that the experience of anger is a trigger of incident CVD events. The mechanism(s) by which provoked anger acutely affects the pathways that underlie atherosclerosis development and progression remain to be fully characterized.
Endothelial dysfunction is a promising mechanism that may explain the link between anger and incident CVD events. Vascular endothelial cells (ECs) play essential roles in maintaining vascular tone and the integrity of blood vessels. Evidence suggests that endothelial dysfunction is an early pathogenic process underlying atherosclerosis development and CVD event onset. Our preliminary findings show in apparently healthy individuals, an anger recall task acutely induces endothelial dysfunction by impairing endothelium-dependent vasodilation, injuring ECs, and disrupting the molecular processes underlying EC reparative capacity. We have additionally found that this task may induce endogenous nitric oxide (NO) inhibition, which plays a central role in aggravating endothelial dysfunction. Therefore, NO inhibition may partially mediate anger-provoked endothelial dysfunction.
Although the strongest data are on anger-provoked CVD events, there is also some evidence that the experience of other core negative emotions such as depressed mood and anxiety may trigger CVD events. Whether the provocation of depressed mood and anxiety acutely induces endothelial dysfunction and NO inhibition remains to be determined. The overall aim of this study is to primarily examine the acute effects of provoked anger and secondarily depressed mood and anxiety on EC health. We will also explore whether NO inhibition partially mediates the acute effects of anger, depressed mood, and anxiety on endothelial function. Examination of these critical pathways will help identify the biological pathways by which the experience of core negative emotions leads to incident CVD risk.
To address these highly significant research questions, we propose a state-of-the-art, laboratory-based, randomized controlled experiment in which 280 participants will be randomized to one of four experimental conditions: an anger recall task (N=70), a depressed mood recall task (N=70), an anxiety recall task (N=70), and an emotionally neutral condition (N=70).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Anger induction | Experimental | Other: Anger InductionThe participant will be asked to undergo a validated anger induction task. |
| Depressed Mood Induction | Experimental | Other: Depressed Mood InductionThe participant will be asked to undergo a validated depression/sadness induction task. |
| Anxiety Induction | Experimental | Other: Anxiety InductionThe participant will be asked to undergo a validated anxiety induction task. |
| Neutral emotion task | Other | Other: Neutral emotion taskThe 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18 and over
- Fluent in English
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anger InductionThe participant is asked to recall an incident in the recent past during which they became moderately to extremely angry, or is asked to read statements out loud evoking moderate to extreme feelings of anger. The participant is asked to take a few moments to bring the details of the incident to mind and, when ready, to describe the incident in great detail to the experimenter. Participants are asked to describe key elements, such as any dialogue that transpired during the incident, along with other details of the incident, particularly regarding the feelings of that particular emotion experienced at the time. In so doing, the experimenter works to re-elicit the emotions that accompanied the original incident. The duration of the negative emotion induction task is 8 minutes. | Other | Anger induction |
| Depressed Mood InductionThe participant will be asked to undergo a validated depression/sadness induction task. | Other | Depressed Mood Induction |
| Anxiety InductionThe participant will be asked to undergo a validated anxiety induction task. | Other | Anxiety Induction |
| Neutral emotion taskThis is a neutral control task that each of the negation emotion induction tasks will be compared to. | Other | Neutral emotion task |
Primary outcome
Endothelium-dependent arterial vasodilation
Time frame: baseline
Circulating EMPs expressing CD62E
Time frame: baseline
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Time frame: baseline
Endothelium-dependent arterial vasodilation
Time frame: 3 mins after end of mood induction
Endothelium-dependent arterial vasodilation
Time frame: 40 mins after end of mood induction
Endothelium-dependent arterial vasodilation
Time frame: 70 mins after end of mood induction
Endothelium-dependent arterial vasodilation
Time frame: 100 mins after end of mood induction
Circulating EMPs expressing CD62E
Time frame: 3 mins after end of mood induction
Circulating EMPs expressing CD62E
Time frame: 40 mins after end of mood induction
Circulating EMPs expressing CD62E
Time frame: 70 mins after end of mood induction
Circulating EMPs expressing CD62E
Time frame: 100 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Time frame: 3 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Time frame: 40 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Time frame: 70 mins after end of mood induction
Circulating early EPCs (KDR+, CD34+, CD133+ cells)
Time frame: 100 mins after end of mood induction
3 secondary outcomes
Circulating EMPs expressing CD31
Time frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction
Circulating EMPs expressing CD51
Time frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction
Self-reported anger, depressed mood, and anxiety
Time frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2022.
- Derived from this study: PubMed 29858417Ensari I, Burg MM, Diaz KM, Fu J, Duran AT, Suls JM, Sumner JA, Monane R, Julian JE, Zhao S, Chaplin WF, Shimbo D. Putative mechanisms Underlying Myocardial infarction onset and Emotions (PUME): a randomised controlled study protocol. BMJ Open. 2018 May 31;8(5):e020525. doi: 10.1136/bmjopen-2017-020525.
- Individual participant dataSharing planned: Undecided
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Healthy Adult Participants
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daichi Shimbo, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anger Induction, Depressed Mood Induction and Anxiety Induction in people with Emotions and Endothelial Dysfunction, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelium-dependent arterial vasodilation (time frame: baseline). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01909895, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2022.