AnhedoniaPhase 1ARIANCT05363527
Aging and Reward System Response to Inflammation and Anxiety Study
A Phase 1 study testing Endotoxin in people with Anhedonia and Inflammation, run by University of California, Los Angeles at 1 site in United States.
Trial summary
The purpose of this study is to use an experimental inflammatory challenge to examine whether older adults with symptoms of anxiety experience loss of pleasure or loss of motivation when they are exposed to inflammation. Read more about this study
- Who is it for?
- Ages 60 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Anhedonia, Inflammation, Anxiety
- What is being tested?
- Endotoxin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2023to 8 Dec 2025
- Phase
- 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 60 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older 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 baseline session)
- Participants will be aged 60 to 80 years.
- 3/4 the participants (n=30) will be those with clinically significant anxiety as defined by a score of 5 or greater on the GAD-7;
- 1/4 the participants (n=10) will be those with low anxiety as defined by a GAD-7 score of <5.
Who cannot join
- Presence of chronic mental or physical illness (except for anxiety)
- History of allergies, autoimmune, liver, or other severe chronic diseases
- Current and regular use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, aspirin, immune modifying drugs, opioid analgesics, statins, antihypertensive drugs, anti-arrhythmic drugs, and antidepressant medications (none in the last 6 months)
- Nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks
- Previous history of fainting during blood draws.
- Claustrophobia
Show all 27Show fewer
- Metal in the body
- 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;
- Presence of comorbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders;
- 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;
- Presence of chronic infection, which may elevate pro-inflammatory cytokines;
- Presence of an acute infectious illness in the two weeks prior to an experimental session.
- Current Axis I psychiatric disorders other than anxiety as determined by the Research Version of the Structured Clinical Interview
- Lifetime history of suicide attempt or inpatient psychiatric admission.
- Sleep Disorders: Current history of sleep apnea or nocturnal myoclonus;
- Phase-shift disorder
- Current and/or past regular use of hormone-containing medications including steroids;
- Current and/or past regular use of non-steroid anti-inflammatory drugs;
- Current and/or past regular use of immune modifying drugs that target specific immune responses such as cytokine antagonists;
- Current and/or past regular use of analgesics such as opioids;
- Current and/or past regular use of cardiovascular medications, including antihypertensive, anti-arrhythmic, antianginal, and anticoagulant drugs;
- Current smoking
- Current excessive caffeine use (>600 mg/day) because of the known effects on pro-inflammatory cytokine levels;
- Evidence of recreational drug use from urine test.
- Body mass index > 35 because of the effects of obesity on proinflammatory cytokine activity
- Any clinically significant abnormality on screening laboratory tests
- Clinically significant abnormalities in electrocardiogram
Trial locations and contacts
1 site in 1 country.
United States1 site
Norman Cousins Center for Psychoneuroimmunology, University of California, Los Angeles
Los Angeles, California, 90095
About this study
Official title: Experimental Model of Depression in Aging: Anxiety, Inflammation, and Reward Mechanisms
The purpose of this study is to use an experimental inflammatory challenge to examine whether older adults with symptoms of anxiety experience loss of pleasure or loss of motivation when they are exposed to inflammation. Loss of pleasure or loss of motivation will be evaluated using self-report questionnaires, computer tasks, and during a brain scan.
Read the detailed description
Participants will undergo phone screening, two in-person visits, and telephone follow-up. The first visit will last 4 hours and the second visit will last 10.5 hours. Phone screening and follow-up will take no longer than 30 minutes.
Phone Screening and Visit #1:
Following phone screening to determine potential eligibility, participants will have an in-person evaluation. Following informed consent in the first session, participants will undergo semi-structured clinical interviews and complete questionnaires to assess medical- and medication histories; current- and past history of psychiatric disorders, and evaluation of behavioral symptoms of anxiety and depression. They will also complete computer tasks that assess motivation and sensitivity to reward. As part of one of these tasks, they will be asked to provide a picture of a loved one, which they will later view during a fMRI scan.
Visit #2 and telephone follow-up:
The second session will be about two weeks later. It will begin at 7:30AM and will involve placement of two intravenous catheters (one in each arm), evaluation of heart rate and blood pressure, administration of endotoxin vs. placebo, repeated blood sampling along with questionnaires about mood and symptoms for approximately 10.5 hours. Two hours post-injection participants will complete a 1-hour brain scan that includes tasks to assess motivation and sensitivity to reward. Study staff will escort the participant to a nearby facility to complete the brain scan. 24 hrs and 2-weeks following this session, study staff will call the subject and ask about physical and mood symptoms, using the same set of items used during the experimental protocol.
- Conditions
- Anhedonia, Inflammation, Anxiety, Aging, Depression
- Being tested
- Endotoxin, Placebo
- Keywords
- anxiety, aging, anhedonia, inflammation
- Medical subject headings
- Anhedonia, Inflammation, Anxiety Disorders, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndotoxinBiological
Endotoxin
PlaceboBiological
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Endotoxin | Experimental | Endotoxin 0.8 ng/kg body weight Receives: Biological: Endotoxin |
| Placebo | Placebo comparator | same volume of 0.9% saline Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neural Indices of Reward Motivation - Anticipatory Reward Response
Task-based functional magnetic resonance imaging (fMRI) will be used to assess reward motivation, as operationalized by ventral striatum (VS) activity during anticipation of monetary reward cue trials vs no-reward cue trials during the Monetary Incentive Delay Task.
Measured: approximately 2 hours post-injection for 7 minutes
Neural Indices of Reward Motivation - Effort-Based Decision Making
Task-based functional magnetic resonance imaging (fMRI) will be used to assess effort-based motivational processing, as assessed by VS, ventromedial prefrontal cortex (vmPFC), and pre-supplementary motor area (pre-SMA) activity with choice phase as event onset during an adapted version of the Effort Expenditure for Rewards Task (EEfRT).
Measured: approximately 2 hours post-injection for 14 minutes
Neural Indices of Monetary Reward Sensitivity during Effort-Based Decision Making
Task-based functional magnetic resonance imaging (fMRI) will be used to assess sensitivity for monetary reward, as operationalized by VS and VMPFC activity during receipt of monetary reward (vs. fixation) and during choice of low vs. high reward trials during the EEfRT.
Measured: approximately 2 hours post-injection for 14 minutes
Neural Indices of Reward Sensitivity for Non-Monetary Reward
Sensitivity for non-monetary reward as assessed by VS and VMPFC activity when viewing positive non-social vs neutral images, and when viewing positive social vs. neutral images, in a positive picture viewing task.
Measured: approximately 2 hours post-injection for 10 minutes
Secondary outcomes (11)
Resting state functional connectivity
Resting-state functional connectivity will be assessed over a 7-minute period, focusing on functional connectivity between the ventromedial prefrontal cortex and ventral striatum.
Measured: 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Social Reward Motivation
Task-based functional magnetic resonance imaging (fMRI) will be used to assess social reward motivation, as operationalized by ventral striatum (VS) activity during anticipation of social reward cue trials vs no-reward cue trials on the Social Incentive Delay Task.
Measured: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Reward Motivation for Close Social Reward
Motivational processing for a close other social reward will be assessed with the Social Incentive Delay Task as VS activity during anticipation of viewing images of a close other (vs no-reward cue).
Measured: approximately 2 hours post-injection for 7 minutes
Behavioral Indices of Reward motivation - close other social reward
Motivational processing for a close other social reward will be assessed as self-reported desire to be around the close other on a scale of 1 (not at all) to 7 (a lot).
Measured: 2 hours post-injection
Monetary Incentive Delay Task -Neural Indices of Monetary Reward Sensitivity
Sensitivity for monetary reward as assessed by VS and VMPFC activity during outcome (reward vs. no-reward) and anticipation (low vs. high reward cues) on the Monetary Incentive Delay task.
Measured: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Social Reward Sensitivity
Sensitivity for social reward as assessed by VS and VMPFC activity during outcomes (reward vs. no-reward) on the Social Incentive Delay Task.
Measured: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Reward Sensitivity for Close Social Reward
Reward sensitivity for a close other will be assessed as VS and VMPFC activity during the outcome phase (close other reward vs no-reward outcomes) and anticipation phase (general social reward vs. close other social reward cue anticipation) on the Social Incentive Delay Task.
Measured: approximately 2 hours post-injection for 7 minutes
Behavioral Indices of Reward Motivation - Effort-Based Decision Making
Motivation for monetary reward is assessed with an Effort Expenditure for Rewards Task (EEfRT); willingness to exert physical effort for monetary reward (i.e., selection of hard vs easy tasks) is the outcome measure with higher willingness indicative of higher motivation.
Measured: Pre-injection and approximately 2 hours post-injection
Behavioral Indices of Reward Sensitivity and Learning - Probabilistic Reward Task
Implicit reward learning and sensitivity to monetary reward is assessed with the probabilistic reward task (PRT); change in the magnitude of response bias from baseline to post-injection is the outcome measure. Higher response bias indicates higher reward sensitivity/learning.
Measured: Pre-injection and approximately 2 hours post-injection
Depressed Mood Subscale of the Profile of Mood States (POMS)
The Depressed Mood Subscale of the POMS is a self-reported assessment of depressed mood in which subjects rate severity of depressed mood using a visual analog scale from 1 to 10 (10 being most severe). Each timepoint is scored and analyses examine the temporal profile of change with assessment every hour
Measured: 10 hours
Motivation for social and non-social reward (interest in activities scale).
This task will evaluate motivation for reward by subjective reports of interest in engaging in a variety of social and non-social activities on a 1 to 5 Likert scale on an hourly basis, with higher score indicating more interest. Each timepoint is scored and analyses examine the temporal profile of change with assessment at baseline and at 1 hour intervals post-injection.
Measured: 10 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2022
- Study start29 Mar 2023
- Primary completion8 Dec 2025
- Study completion8 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnhedoniaStudies 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
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Endotoxin vs. Placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Chloe Boyle, PhD, University of California, Los Angeles
- Investigators
- Chloe C Boyle, PHD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05363527
- Sponsor's protocol ID
- K01AG072049
- Other IDs
- 1K01AG072049-01A1
- Acronym
- ARIA
- Status last verified
- Dec 2025
- First submitted
- 2 May 2022
- Last updated
- 11 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be available to users upon request, provided the investigators are working under an institution with a Federal Wide Assurance (FWA). All requests for transfer of materials for research purposes will be made through a UCLA onlineMTA. Persons requesting access will be required to complete a data-sharing agreement providing for the maintenance of the confidentiality of research participants, describing use to which the data will be put, and requiring acknowledgement of the source of the data and its underlying NIA funding. The names and institutions of persons either given or denied access to the data, and the bases for such decisions, will be summarized in annual progress reports.
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Experimental Model of Depression in Aging: Anxiety, Inflammation, and Reward Mechanisms
- ClinicalTrials.gov ID
- NCT05363527
- Acronym / sponsor ID
- ARIA / K01AG072049
- Conditions
- Anhedonia, Inflammation, Anxiety, Aging, Depression
- Keywords
- anxiety, aging, anhedonia, inflammation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 29 Mar 2023 (actual)
- Primary completion
- 8 Dec 2025 (actual)
- Study completion
- 8 Dec 2025 (actual)
- First posted
- 6 May 2022 (actual)
- 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.
The purpose of this study is to use an experimental inflammatory challenge to examine whether older adults with symptoms of anxiety experience loss of pleasure or loss of motivation when they are exposed to inflammation. Loss of pleasure or loss of motivation will be evaluated using self-report questionnaires, computer tasks, and during a brain scan.
Detailed description
Participants will undergo phone screening, two in-person visits, and telephone follow-up. The first visit will last 4 hours and the second visit will last 10.5 hours. Phone screening and follow-up will take no longer than 30 minutes.
Phone Screening and Visit #1:
Following phone screening to determine potential eligibility, participants will have an in-person evaluation. Following informed consent in the first session, participants will undergo semi-structured clinical interviews and complete questionnaires to assess medical- and medication histories; current- and past history of psychiatric disorders, and evaluation of behavioral symptoms of anxiety and depression. They will also complete computer tasks that assess motivation and sensitivity to reward. As part of one of these tasks, they will be asked to provide a picture of a loved one, which they will later view during a fMRI scan.
Visit #2 and telephone follow-up:
The second session will be about two weeks later. It will begin at 7:30AM and will involve placement of two intravenous catheters (one in each arm), evaluation of heart rate and blood pressure, administration of endotoxin vs. placebo, repeated blood sampling along with questionnaires about mood and symptoms for approximately 10.5 hours. Two hours post-injection participants will complete a 1-hour brain scan that includes tasks to assess motivation and sensitivity to reward. Study staff will escort the participant to a nearby facility to complete the brain scan. 24 hrs and 2-weeks following this session, study staff will call the subject and ask about physical and mood symptoms, using the same set of items used during the experimental protocol.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Endotoxin vs. Placebo
| Arm | Type | Receives |
|---|---|---|
| Endotoxin | Experimental | Biological: EndotoxinEndotoxin 0.8 ng/kg body weight |
| Placebo | Placebo comparator | Biological: Placebosame volume of 0.9% saline |
Who may qualify
- Ages
- 60 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participants will be required to be in good general health (as evaluated during the phone and in-person baseline session)
- Participants will be aged 60 to 80 years.
- 3/4 the participants (n=30) will be those with clinically significant anxiety as defined by a score of 5 or greater on the GAD-7;
- 1/4 the participants (n=10) will be those with low anxiety as defined by a GAD-7 score of <5.
Key exclusion criteria (27 listed)
- Presence of chronic mental or physical illness (except for anxiety)
- History of allergies, autoimmune, liver, or other severe chronic diseases
- Current and regular use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, aspirin, immune modifying drugs, opioid analgesics, statins, antihypertensive drugs, anti-arrhythmic drugs, and antidepressant medications (none in the last 6 months)
- Nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks
- Previous history of fainting during blood draws.
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 |
|---|---|---|
| EndotoxinEndotoxin | Biological | Endotoxin |
| PlaceboPlacebo | Biological | Placebo |
Primary outcome
Neural Indices of Reward Motivation - Anticipatory Reward Response
Time frame: approximately 2 hours post-injection for 7 minutes
Task-based functional magnetic resonance imaging (fMRI) will be used to assess reward motivation, as operationalized by ventral striatum (VS) activity during anticipation of monetary reward cue trials vs no-reward cue trials during the Monetary Incentive Delay Task.
Neural Indices of Reward Motivation - Effort-Based Decision Making
Time frame: approximately 2 hours post-injection for 14 minutes
Task-based functional magnetic resonance imaging (fMRI) will be used to assess effort-based motivational processing, as assessed by VS, ventromedial prefrontal cortex (vmPFC), and pre-supplementary motor area (pre-SMA) activity with choice phase as event onset during an adapted version of the Effort Expenditure for Rewards Task (EEfRT).
Neural Indices of Monetary Reward Sensitivity during Effort-Based Decision Making
Time frame: approximately 2 hours post-injection for 14 minutes
Task-based functional magnetic resonance imaging (fMRI) will be used to assess sensitivity for monetary reward, as operationalized by VS and VMPFC activity during receipt of monetary reward (vs. fixation) and during choice of low vs. high reward trials during the EEfRT.
Neural Indices of Reward Sensitivity for Non-Monetary Reward
Time frame: approximately 2 hours post-injection for 10 minutes
Sensitivity for non-monetary reward as assessed by VS and VMPFC activity when viewing positive non-social vs neutral images, and when viewing positive social vs. neutral images, in a positive picture viewing task.
11 secondary outcomes
Resting state functional connectivity
Time frame: 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Social Reward Motivation
Time frame: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Reward Motivation for Close Social Reward
Time frame: approximately 2 hours post-injection for 7 minutes
Behavioral Indices of Reward motivation - close other social reward
Time frame: 2 hours post-injection
Monetary Incentive Delay Task -Neural Indices of Monetary Reward Sensitivity
Time frame: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Social Reward Sensitivity
Time frame: approximately 2 hours post-injection for 7 minutes
Social Incentive Delay Task - Neural Indices of Reward Sensitivity for Close Social Reward
Time frame: approximately 2 hours post-injection for 7 minutes
Behavioral Indices of Reward Motivation - Effort-Based Decision Making
Time frame: Pre-injection and approximately 2 hours post-injection
Behavioral Indices of Reward Sensitivity and Learning - Probabilistic Reward Task
Time frame: Pre-injection and approximately 2 hours post-injection
Depressed Mood Subscale of the Profile of Mood States (POMS)
Time frame: 10 hours
Motivation for social and non-social reward (interest in activities scale).
Time frame: 10 hours
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 11 Dec 2025.
- Individual participant dataSharing planned: Yes. De-identified data will be available to users upon request, provided the investigators are working under an institution with a Federal Wide Assurance (FWA). All requests for transfer of materials for research purposes will be made through a UCLA onlineMTA. Persons requesting access will be required to complete a data-sharing agreement providing for the maintenance of the confidentiality of research participants, describing use to which the data will be put, and requiring acknowledgement of the source of the data and its underlying NIA funding. The names and institutions of persons either given or denied access to the data, and the bases for such decisions, will be summarized in annual progress reports.
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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.
Chloe C Boyle, PHD 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 Phase 1 study testing Endotoxin in people with Anhedonia and Inflammation, 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 4 inclusion and 27 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 11 Dec 2025. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Neural Indices of Reward Motivation - Anticipatory Reward Response (time frame: approximately 2 hours post-injection for 7 minutes). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Dec 2025.