Aging and Reward System Response to Inflammation and Anxiety Study

NCT05363527 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: K01AG0720491K01AG072049-01A1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. Loss of pleasure or loss of motivation will be evaluated using self-report questionnaires, computer tasks, and during a brain scan.

Conditions

Anhedonia; Inflammation; Anxiety; Aging; Depression

Keywords

anxiety; aging; anhedonia; inflammation

Outcome Measures

Primary Outcomes (4)

• 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.

  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).

  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.

  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.

  approximately 2 hours post-injection for 10 minutes

Secondary Outcomes (11)

• Resting state functional connectivity

  2 hours post-injection for 7 minutes

• Social Incentive Delay Task - Neural Indices of Social Reward Motivation

  approximately 2 hours post-injection for 7 minutes

• Social Incentive Delay Task - Neural Indices of Reward Motivation for Close Social Reward

  approximately 2 hours post-injection for 7 minutes

• Behavioral Indices of Reward motivation - close other social reward

  2 hours post-injection

• Monetary Incentive Delay Task -Neural Indices of Monetary Reward Sensitivity

  approximately 2 hours post-injection for 7 minutes

Other Outcomes (11)

• Behavioral Indices of Reward Motivation and Sensitivity with Incentive Delay Tasks

  approximately 2 hours post-injection for 14 minutes

• Behavioral Indices of Reward Sensitivity - Positive Images Task

  approximately 2 hours post-injection for 10 minutes

• Behavioral Indices of Reward Sensitivity - EEfRT

  Pre-injection and 2 hours post-injection

Study Arms (2)

Endotoxin

EXPERIMENTAL

Endotoxin 0.8 ng/kg body weight

Biological: Endotoxin

Placebo

PLACEBO COMPARATOR

same volume of 0.9% saline

Biological: Placebo

Interventions

Placebo BIOLOGICAL

Placebo

Placebo

Endotoxin BIOLOGICAL

Endotoxin

Endotoxin

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• /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;
• /4 the participants (n=10) will be those with low anxiety as defined by a GAD-7 score of \<5.

You may not qualify if:

• 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
• 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;

Sponsors & Collaborators

• National Institute on Aging (NIA): collaborator
• University of California, Los Angeles: lead

Study Sites (1)

Norman Cousins Center for Psychoneuroimmunology, University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Anhedonia; Inflammation; Anxiety Disorders; Depression

Interventions

Endotoxins

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Chloe C Boyle, PHD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded infusion
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Assistant Professor

Model Details: Endotoxin vs. Placebo

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 6, 2022
• Study Start: March 29, 2023
• Primary Completion: December 8, 2025
• Study Completion: December 8, 2025
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available by the on-line publication date once the data has been accepted for publication. All submitted data will conform to relevant data and terminology standards. This data sharing policy is intended to allow investigators sufficient time for data verification, and for submission of primary publications based on the collected data. We will identify where the data will be available, and how to access the data (i.e., by contacting Dr. Boyle directly), in any publication or presentation by Dr. Boyle and her mentorship team. Finally, we will acknowledge the funding source in any and all publications and presentations using these data.
• Access Criteria: * investigators must be working under an institution with a Federal Wide Assurance (FWA); * 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.

Locations

US (1)