Trial Outcomes & Findings for Sleep and Healthy Aging Research on Depression for Younger Women (NCT NCT03848715)
NCT ID: NCT03848715
Last Updated: 2026-01-27
Results Overview
Implicit reward learning and sensitivity to monetary reward is assessed with the probabilistic reward task (PRT) a behavioral computer task; change in the magnitude of response bias from baseline to post-injection is the outcome measure. More positive response bias indicates a bias towards the more frequently reward stimuli (a better outcome); more negative response bias indicates a bias towards the less frequently reward stimuli (a worse outcome). This is not a standardized scale with minimum and maximum values. Response bias is calculated using a formula from signal detection theory and is a logarithmic ratio derived from choice frequencies. The formula is log b=1/2log((Rich-correct+.5) \*(Lean-incorrect+.5)/(rich-incorrect+.5) \* (lean-incorrect+.5)), where rich refers to the more frequently rewarded option and lean refers to the less frequently rewarded option.
COMPLETED
PHASE1
40 participants
Baseline and post-injection (2.25 hrs)
2026-01-27
Participant Flow
Clinical hold on LPS by FDA
Participant milestones
| Measure |
Endotoxin
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
22
|
|
Overall Study
COMPLETED
|
18
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sleep and Healthy Aging Research on Depression for Younger Women
Baseline characteristics by cohort
| Measure |
Endotoxin
n=18 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=22 Participants
same volume of 0.9% saline
Placebo: Placebo
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
30 years
n=25 Participants
|
35 years
n=25 Participants
|
33 years
n=50 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=25 Participants
|
22 Participants
n=25 Participants
|
40 Participants
n=50 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=25 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=50 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=25 Participants
|
4 Participants
n=25 Participants
|
8 Participants
n=50 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=25 Participants
|
18 Participants
n=25 Participants
|
32 Participants
n=50 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=25 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=50 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=25 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=50 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=25 Participants
|
2 Participants
n=25 Participants
|
7 Participants
n=50 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=25 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=50 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=25 Participants
|
4 Participants
n=25 Participants
|
6 Participants
n=50 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=25 Participants
|
11 Participants
n=25 Participants
|
19 Participants
n=50 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=25 Participants
|
5 Participants
n=25 Participants
|
8 Participants
n=50 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=25 Participants
|
0 Participants
n=25 Participants
|
0 Participants
n=50 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=25 Participants
|
22 participants
n=25 Participants
|
40 participants
n=50 Participants
|
PRIMARY outcome
Timeframe: Baseline and post-injection (2.25 hrs)Population: For the Probabilistic Reward Task data are cleaned according to pre-specified quality controlled (QC) guidelines; data that do not meet these QC requirements are not included (e.g., participants who have accuracy less than 50%)
Implicit reward learning and sensitivity to monetary reward is assessed with the probabilistic reward task (PRT) a behavioral computer task; change in the magnitude of response bias from baseline to post-injection is the outcome measure. More positive response bias indicates a bias towards the more frequently reward stimuli (a better outcome); more negative response bias indicates a bias towards the less frequently reward stimuli (a worse outcome). This is not a standardized scale with minimum and maximum values. Response bias is calculated using a formula from signal detection theory and is a logarithmic ratio derived from choice frequencies. The formula is log b=1/2log((Rich-correct+.5) \*(Lean-incorrect+.5)/(rich-incorrect+.5) \* (lean-incorrect+.5)), where rich refers to the more frequently rewarded option and lean refers to the less frequently rewarded option.
Outcome measures
| Measure |
Endotoxin
n=14 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=17 Participants
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
Non-social (Monetary) Reward Response (Reward Learning and Sensitivity)
Baseline (pre-injection) PRT TASK
|
.563 response bias
Standard Deviation .292
|
.307 response bias
Standard Deviation .409
|
|
Non-social (Monetary) Reward Response (Reward Learning and Sensitivity)
Post-injection PRT TASK
|
.309 response bias
Standard Deviation .478
|
.366 response bias
Standard Deviation .460
|
PRIMARY outcome
Timeframe: Baseline and post-injection (2.1 hrs)Motivation for monetary reward is assessed with a 10-minute version of the Effort Expenditure for Rewards Task (EEfRT), a behavioral computer task; change in the amount of hard trials chosen (relative to total trials) from baseline to post-injection is the outcome measure. The task is analyzed using generalized estimating equations (GEE) with a binary outcome; outcome values at each timepoint therefore range from 0 to 1, with higher numbers indicating higher motivation (a better outcome). The predictor for the GEE model is a time (coded as 0 and 1) by condition (coded as 0 and 1) interaction term. A negative result in the boxes below for each condition separately indicates a pre-to post-injection decrease in the proportion of hard trials chosen.
Outcome measures
| Measure |
Endotoxin
n=18 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=22 Participants
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
Non-social (Monetary) Reward Response (Reward Motivation)
|
-.3597425 Proportion of hard trials
Interval -0.6121048 to -0.1073803
|
-.0876787 Proportion of hard trials
Interval -0.2934619 to 0.1181044
|
PRIMARY outcome
Timeframe: Baseline and post-injection (2.1 hrs)Sensitivity for monetary reward is assessed with a 10-minute version of the Effort Expenditure for Rewards Task (EEfRT) a behavioral computer task, tested as the strength of the association between increases in potential monetary reward for hard trials and selection of hard (vs) easy trials during the task. This is tested using generalized estimating equations, with condition (LPS vs. placebo) by time (pre vs post-injection) by reward magnitude (ranges from $1-$4.12) predicting hard (vs easy) trial choice. More positive values indicate higher reward sensitivity ( a better outcome), and lower values indicate lower reward sensitivity. The unit of measurement for the task is the proportion of hard trials chosen; the unit of measurement for the reward sensitivity outcome is a beta coefficient. For example, a positive coefficient for reward magnitude in the GEE output means that as the reward amount increases by one unit (e.g., $1), the odds of choosing the high-effort option increase.
Outcome measures
| Measure |
Endotoxin
n=18 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=22 Participants
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
Non-social (Monetary) Reward Response (Reward Sensitivity)
|
-.0525937 Proportion of hard trials chosen
Interval -0.1125722 to 0.0073848
|
.0521303 Proportion of hard trials chosen
Interval 0.0032571 to 0.1010036
|
PRIMARY outcome
Timeframe: Baseline and post-injection (2.7 hrs)Sensitivity to general social reward cues (i.e., response to positive emotional faces) assessed as positive attentional bias with an emotional dot probe task. Attentional bias is assessed by measuring reaction times to targets that appear in the same location as emotional (e.g., happy faces) versus neutral cues (e.g., neutral faces). Outcomes are change from baseline to post-injection in attentional bias towards positive vs neutral faces. Higher positive attentional bias scores indicate higher sensitivity to reward; negative attentional bias score indicate less sensitivity to reward. A score of 0 indicates no bias. The attentional bias score is derived by subtracting the reaction time in ms on congruent trials (dot replaces an emotional face) from the reaction time on incongruent trials (dot replaces the neutral face).
Outcome measures
| Measure |
Endotoxin
n=16 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=20 Participants
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
General Social Reward Response (Reward Sensitivity Via Emotional Dot Probe)
|
11.85463 milliseconds
Standard Deviation 18.61149
|
5.806407 milliseconds
Standard Deviation 38.32138
|
PRIMARY outcome
Timeframe: Baseline and post-injection (2.8 hrs)Sensitivity to general social reward cues (i.e., response to positive emotional faces) assessed as positive emotion detection with a face morphing task. The outcome is the absolute change from baseline to post-injection in the percent of accurate responses. Higher accuracy is an indicator of higher sensitivity to reward and lower accuracy is an indicator of lower sensitivity to reward.
Outcome measures
| Measure |
Endotoxin
n=18 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=19 Participants
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
General Social Reward Response (Reward Sensitivity Via Face Morphing Task)
|
.0092593 Percentage of accuracy
Standard Error .0190538
|
.0657895 Percentage of accuracy
Standard Error .0185456
|
PRIMARY outcome
Timeframe: Baseline and post-injection (2 hrs)Motivation for general social reward is assessed via self-report; participants rate their desire to engage in 3 different activities, one of which is social, on a 1 (not at all) to 10 (extremely) Likert scale.; change in desire for the social activity from baseline to post-injection is the outcome variable. Higher values indicate higher motivation.
Outcome measures
| Measure |
Endotoxin
n=17 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=21 Participants
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
General Social Reward Response (Social Reward Motivation)
|
-2.94 change in score on a scale
Standard Deviation 3.40
|
-.29 change in score on a scale
Standard Deviation 1.65
|
SECONDARY outcome
Timeframe: Hourly, from pre-injection (T0) to 9 hours later (T9)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. The outcome reported below is the mean score at 2-hours post-injection, which is when the response to endotoxin is known to peak. Higher values indicate more depressive symptoms.
Outcome measures
| Measure |
Endotoxin
n=18 Participants
Endotoxin 0.8 ng/kg body weight; 1 infusion
Endotoxin: Endotoxin
|
Placebo
n=22 Participants
same volume of 0.9% saline
Placebo: Placebo
|
|---|---|---|
|
Depressed Mood Subscale of the Profile of Mood States (POMS)
|
6.939871 score on a scale
Standard Error 1.952918
|
2.680794 score on a scale
Standard Error 1.762826
|
SECONDARY outcome
Timeframe: Post-injection (2.9 hrs)Participants spend 5 minutes talking about a "close other" to a research assistant trained in reflective listening and provide ratings of current negative and positive emotion on visual analogue scales (0=not at all; 100=extremely) using items from the Profile of Mood States. Outcome variables are change in self-report positive emotion from pre to post-discussion, and percentage of positive and negative emotional words used during the discussion (scored with Linguistic Inquiry and Word Count Software). Higher positive emotion and higher percentage of positive words indicates a greater social reward response.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 14 days (7 days pre-injection; 7 days post-injection).Participants indicate the extent to which they enjoyed 10 activities (social, non-social, close social) on a 0-100 visual analogue scale (0= not at all; 100=extremely) at five random times during the day; change in enjoyment in each of the domains from pre to post-experimental session is the outcome for consummatory reward. Higher values indicate higher reward response.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and post-injection (1.9 hrs)Count of eye blinks (resting eye blink rate; EBR) over a five minute period; the outcome is change in EBR from pre to post-injection. Higher values indicate higher dopaminergic activity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 14 days (7 days pre-injection; 7 days post-injection).Participants rate how much they are currently looking forward to different categories of rewarding activities on an analogue scale (0= not at all; 100=extremely); change from pre to post-experimental session is the outcome for anticipatory reward. Higher values indicate higher reward response.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: post-injection (approximately 3 hrs)Participants complete a 30 minute standardized emotion regulation task that includes two phases: a reactivity phase and a regulation phase, and assesses the ability to down-regulate negative emotional response to standardized images, using instructed reappraisal strategies. The dependent variable is the degree to which self-reported emotion changes when reacting to versus reappraising emotion stimuli. Participants rate how negative they feel on a 0 (not at all) to 100 (extremely) visual analogue scale before and after film clips. The change in negative emotion when reacting is compared to the change in negative emotion when regulating. More positive values indicate better emotion regulation.
Outcome measures
Outcome data not reported
Adverse Events
Endotoxin
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place