DepressionEarly Phase 1NCT01671150
Inflammation-Induced Depressed Mood: The Role of Social Neurocognitive Mechanisms
A Early Phase 1 study testing endotoxin in people with Depression, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Depressive disorders occur at a high rate in patients with inflammatory disorders, with a point prevalence of 15-29%, which is two to three times greater than that observed in the general population. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression
- What is being tested?
- endotoxin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Aug 2013
- Phase
- Early Phase 1
- 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 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants will be required to be in good general health (as evaluated during the phone and in-person screening sessions described below), and to be between 18-50 years of age. All participants will be required to be fluent in English and to be right-handed.
Who cannot join
- Following a structured telephone interview, prospective participants with the following conditions will not advance to the in-person screening session: claustrophobia or presence of metal in their body (relevant for the neuroimaging component of the study), pregnant or planning to become pregnant in the next 6 months, presence of chronic mental or physical illness, history of allergies, autoimmune, liver, or other severe chronic diseases, current and regular use of prescription medications, nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks, or previous history of fainting during blood draws.
- Furthermore, the absence of significant health problems or medication use history will be confirmed by an in-person screening session. Any participant who has any of the following conditions will be ineligible for the study: Medical conditions. (1) presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders; (2) presence of co-morbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders; (3) presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk; (4) presence of chronic infection, which may elevate proinflammatory cytokines; (5) presence of an acute infectious illness in the two weeks prior to an experimental session. Psychiatric Disorders. (6) current and/or lifetime history of a major Depressive Disorder or other DSM-IV psychiatric disorder (e.g. substance dependence) due to the known effects of major depression and/or substance dependence on inflammation. (Absence of a psychiatric diagnosis will be based on a structured psychiatric interview (Structured Clinical Interview for DSM-IV Diagnosis: SCID; First et al., 1996).) Medication and substance use. (7) current and/or past regular use of hormone-containing medications including steroids; (8) current and/or past regular use of non-steroid anti-inflammatory drugs; (9) current and/or past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists; (10) current and/or past regular use of analgesics such as opioids; (11) current and/or past regular use of psychotropic medications, including selective serotinergic reuptake inhibitors, antidepressants, anxiolytics, hypnotics, sedatives and barbiturates. Health factors. (12) current smokers or excessive caffeine users (>600 mg/day) because of known effects on proinflammatory cytokine levels; (13) body mass index (BMI) greater than 35, (14) shows evidence of drug use from a positive urine test, (15) has a positive pregnancy test, if female, or (16) shows any abnormalities on screening laboratory tests.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Clinical & Translational Research Center
Los Angeles, California, 90095
About this study
Depressive disorders occur at a high rate in patients with inflammatory disorders, with a point prevalence of 15-29%, which is two to three times greater than that observed in the general population. Substantial evidence has shown that inflammation and increases in proinflammatory cytokine activity play a critical role in the onset and perpetuation of depression and depressive symptoms (e.g. insomnia, fatigue) in those who are co-morbid for inflammatory disorders. Consistent with this, experimental work has shown that an inflammatory challenge can increase depressed mood in an otherwise healthy sample. Based on these findings, there has been a growing interest in whether inflammatory processes can contribute to depression in a causal manner and how these effects might occur.
Given the observation that inflammatory processes trigger social withdrawal, coupled with evidence that feelings of 'social disconnection' play a critical role in the onset and perpetuation of (non-inflammatory forms of) depression, it is surprising that the social psychological consequences of inflammation and their contribution to depression have not been more fully explored. Here, we suggest that inflammation may increase feelings of social disconnection and that these social psychological changes may be an important contributor to inflammation-associated depression. Indeed, preliminary data demonstrated that an experimentally-induced inflammatory challenge (endotoxin) led to increases in self-reported feelings of social disconnection (e.g., "I feel disconnected from others") in addition to increases in depressed mood. Aside from these findings, however, there are no studies that have explored the effect of inflammatory processes on social experience in humans. The over-arching objective of this proposal is to explore the experiential and neural correlates of inflammatory-induced changes in social experience (e.g., feelings of social disconnection), which may provide a critical missing link in understanding the relationship between inflammation and depression.
Participants (n=100) will be randomly assigned to receive either endotoxin or placebo and will then be monitored for the next six hours. Blood draws to assess cytokine levels as well as self-reported feelings of social disconnection and depressed mood will be collected hourly. In addition, at the time of peak cytokine response, participants will complete a neuroimaging session to examine the effect of inflammatory challenge on neural sensitivity to social rejection and social acceptance. It is hypothesized that endotoxin will increase feelings of social disconnection over time, and that the underlying neural sensitivities that give rise to these feelings (e.g., increased neural sensitivity to social rejection; decreased neural sensitivity to social acceptance) will contribute to inflammatory-induced depressed mood.
- Conditions
- Depression
- Being tested
- endotoxin
- Keywords
- inflammation, depression, social cognition, neural activity
- Medical subject headings
- Depression, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
endotoxinDrug
Low-dose endotoxin (0.8 ng/kg of body weight): EC.O:113 administered once
| Study group | Role | What they receive |
|---|---|---|
| Placebo control | Placebo comparator | half of the participants will receive a placebo control Receives: Drug: endotoxin |
| Endotoxin (Inflammatory challenge) | Active comparator | Not described Receives: Drug: endotoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in depressed mood from baseline
Measured: at baseline and then at 1,2,3,4,5,and 6 hours after drug administration
Secondary outcomes (1)
Neural activity to negative and positive social feedback
Measured: 2 hours after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2012 (estimated)
- Study startMar 2011
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Naomi Eisenberger, University of California, Los Angeles
- Investigators
- Naomi Eisenberger, PhD, Principal investigator, University of California, Los AngelesMichael Irwin, M.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01671150
- Sponsor's protocol ID
- Endotoxin 2
- Other IDs
- R01MH091352
- Status last verified
- Jun 2014
- First submitted
- 11 Jul 2012
- Last updated
- 18 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kruse JL, Boyle CC, Olmstead R, Breen EC, Tye SJ, Eisenberger NI, Irwin MR. Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial. Sci Rep. 2022 Jul 24;12(1):12627. doi: 10.1038/s41598-022-16364-3.
PubMed 35871638Moieni M, Muscatell KA, Jevtic I, Breen EC, Irwin MR, Eisenberger NI. Sex Differences in the Effect of Inflammation on Subjective Social Status: A Randomized Controlled Trial of Endotoxin in Healthy Young Adults. Front Psychol. 2019 Oct 1;10:2167. doi: 10.3389/fpsyg.2019.02167. eCollection 2019.
PubMed 31632316Moieni M, Tan KM, Inagaki TK, Muscatell KA, Dutcher JM, Jevtic I, Breen EC, Irwin MR, Eisenberger NI. Sex Differences in the Relationship Between Inflammation and Reward Sensitivity: A Randomized Controlled Trial of Endotoxin. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jul;4(7):619-626. doi: 10.1016/j.bpsc.2019.03.010. Epub 2019 Apr 3.
PubMed 31103547Moieni M, Irwin MR, Jevtic I, Breen EC, Cho HJ, Arevalo JM, Ma J, Cole SW, Eisenberger NI. Trait sensitivity to social disconnection enhances pro-inflammatory responses to a randomized controlled trial of endotoxin. Psychoneuroendocrinology. 2015 Dec;62:336-42. doi: 10.1016/j.psyneuen.2015.08.020. Epub 2015 Aug 28.
PubMed 26360770Moieni M, Irwin MR, Jevtic I, Breen EC, Eisenberger NI. Inflammation impairs social cognitive processing: A randomized controlled trial of endotoxin. Brain Behav Immun. 2015 Aug;48:132-8. doi: 10.1016/j.bbi.2015.03.002. Epub 2015 Mar 10.
PubMed 25770082
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammation-Induced Depressed Mood: The Role of Social Neurocognitive Mechanisms
- ClinicalTrials.gov ID
- NCT01671150
- Acronym / sponsor ID
- Endotoxin 2
- Conditions
- Depression
- Keywords
- inflammation, depression, social cognition, neural activity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Mar 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 23 Aug 2012 (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.
Depressive disorders occur at a high rate in patients with inflammatory disorders, with a point prevalence of 15-29%, which is two to three times greater than that observed in the general population. Substantial evidence has shown that inflammation and increases in proinflammatory cytokine activity play a critical role in the onset and perpetuation of depression and depressive symptoms (e.g. insomnia, fatigue) in those who are co-morbid for inflammatory disorders. Consistent with this, experimental work has shown that an inflammatory challenge can increase depressed mood in an otherwise healthy sample. Based on these findings, there has been a growing interest in whether inflammatory processes can contribute to depression in a causal manner and how these effects might occur.
Given the observation that inflammatory processes trigger social withdrawal, coupled with evidence that feelings of 'social disconnection' play a critical role in the onset and perpetuation of (non-inflammatory forms of) depression, it is surprising that the social psychological consequences of inflammation and their contribution to depression have not been more fully explored. Here, we suggest that inflammation may increase feelings of social disconnection and that these social psychological changes may be an important contributor to inflammation-associated depression. Indeed, preliminary data demonstrated that an experimentally-induced inflammatory challenge (endotoxin) led to increases in self-reported feelings of social disconnection (e.g., "I feel disconnected from others") in addition to increases in depressed mood. Aside from these findings, however, there are no studies that have explored the effect of inflammatory processes on social experience in humans. The over-arching objective of this proposal is to explore the experiential and neural correlates of inflammatory-induced changes in social experience (e.g., feelings of social disconnection), which may provide a critical missing link in understanding the relationship between inflammation and depression.
Participants (n=100) will be randomly assigned to receive either endotoxin or placebo and will then be monitored for the next six hours. Blood draws to assess cytokine levels as well as self-reported feelings of social disconnection and depressed mood will be collected hourly. In addition, at the time of peak cytokine response, participants will complete a neuroimaging session to examine the effect of inflammatory challenge on neural sensitivity to social rejection and social acceptance. It is hypothesized that endotoxin will increase feelings of social disconnection over time, and that the underlying neural sensitivities that give rise to these feelings (e.g., increased neural sensitivity to social rejection; decreased neural sensitivity to social acceptance) will contribute to inflammatory-induced depressed mood.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo control | Placebo comparator | Drug: endotoxinhalf of the participants will receive a placebo control |
| Endotoxin (Inflammatory challenge) | Active comparator | Drug: endotoxin |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Participants will be required to be in good general health (as evaluated during the phone and in-person screening sessions described below), and to be between 18-50 years of age. All participants will be required to be fluent in English and to be right-handed.
Key exclusion criteria (2 listed)
- Following a structured telephone interview, prospective participants with the following conditions will not advance to the in-person screening session: claustrophobia or presence of metal in their body (relevant for the neuroimaging component of the study), pregnant or planning to become pregnant in the next 6 months, presence of chronic mental or physical illness, history of allergies, autoimmune, liver, or other severe chronic diseases, current and regular use of prescription medications, nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks, or previous history of fainting during blood draws.
- Furthermore, the absence of significant health problems or medication use history will be confirmed by an in-person screening session. Any participant who has any of the following conditions will be ineligible for the study: Medical conditions. (1) presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders; (2) presence of co-morbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders; (3) presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk; (4) presence of chronic infection, which may elevate proinflammatory cytokines; (5) presence of an acute infectious illness in the two weeks prior to an experimental session. Psychiatric Disorders. (6) current and/or lifetime history of a major Depressive Disorder or other DSM-IV psychiatric disorder (e.g. substance dependence) due to the known effects of major depression and/or substance dependence on inflammation. (Absence of a psychiatric diagnosis will be based on a structured psychiatric interview (Structured Clinical Interview for DSM-IV Diagnosis: SCID; First et al., 1996).) Medication and substance use. (7) current and/or past regular use of hormone-containing medications including steroids; (8) current and/or past regular use of non-steroid anti-inflammatory drugs; (9) current and/or past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists; (10) current and/or past regular use of analgesics such as opioids; (11) current and/or past regular use of psychotropic medications, including selective serotinergic reuptake inhibitors, antidepressants, anxiolytics, hypnotics, sedatives and barbiturates. Health factors. (12) current smokers or excessive caffeine users (>600 mg/day) because of known effects on proinflammatory cytokine levels; (13) body mass index (BMI) greater than 35, (14) shows evidence of drug use from a positive urine test, (15) has a positive pregnancy test, if female, or (16) shows any abnormalities on screening laboratory tests.
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 |
|---|---|---|
| endotoxinLow-dose endotoxin (0.8 ng/kg of body weight): EC.O:113 administered once | Drug | Endotoxin (Inflammatory challenge), Placebo control |
Primary outcome
Change in depressed mood from baseline
Time frame: at baseline and then at 1,2,3,4,5,and 6 hours after drug administration
1 secondary outcome
Neural activity to negative and positive social feedback
Time frame: 2 hours after drug administration
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 18 Jun 2014.
- Derived from this study: PubMed 35871638Kruse JL, Boyle CC, Olmstead R, Breen EC, Tye SJ, Eisenberger NI, Irwin MR. Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial. Sci Rep. 2022 Jul 24;12(1):12627. doi: 10.1038/s41598-022-16364-3.
- Derived from this study: PubMed 31632316Moieni M, Muscatell KA, Jevtic I, Breen EC, Irwin MR, Eisenberger NI. Sex Differences in the Effect of Inflammation on Subjective Social Status: A Randomized Controlled Trial of Endotoxin in Healthy Young Adults. Front Psychol. 2019 Oct 1;10:2167. doi: 10.3389/fpsyg.2019.02167. eCollection 2019.
- Derived from this study: PubMed 31103547Moieni M, Tan KM, Inagaki TK, Muscatell KA, Dutcher JM, Jevtic I, Breen EC, Irwin MR, Eisenberger NI. Sex Differences in the Relationship Between Inflammation and Reward Sensitivity: A Randomized Controlled Trial of Endotoxin. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jul;4(7):619-626. doi: 10.1016/j.bpsc.2019.03.010. Epub 2019 Apr 3.
- Derived from this study: PubMed 26360770Moieni M, Irwin MR, Jevtic I, Breen EC, Cho HJ, Arevalo JM, Ma J, Cole SW, Eisenberger NI. Trait sensitivity to social disconnection enhances pro-inflammatory responses to a randomized controlled trial of endotoxin. Psychoneuroendocrinology. 2015 Dec;62:336-42. doi: 10.1016/j.psyneuen.2015.08.020. Epub 2015 Aug 28.
- Derived from this study: PubMed 25770082Moieni M, Irwin MR, Jevtic I, Breen EC, Eisenberger NI. Inflammation impairs social cognitive processing: A randomized controlled trial of endotoxin. Brain Behav Immun. 2015 Aug;48:132-8. doi: 10.1016/j.bbi.2015.03.002. Epub 2015 Mar 10.
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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.
Naomi Eisenberger, PhD principal investigator
University of California, Los Angeles
Michael Irwin, M.D. principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing endotoxin in people with Depression, run by University of California, Los Angeles 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 1 inclusion and 2 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 18 Jun 2014. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change in depressed mood from baseline (time frame: at baseline and then at 1,2,3,4,5,and 6 hours after drug administration). 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 NCT01671150, which also lists 5 linked publications.
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 18 Jun 2014.