Trial Outcomes & Findings for Lipopolysaccharide (LPS) Challenge in Depression (NCT NCT03142919)
NCT ID: NCT03142919
Last Updated: 2025-07-02
Results Overview
The SHAPS is a 14-item self-administered questionnaire, with each item scored from 1-4 (strongly agree through strongly disagree; range 14-56), with higher scores indicating greater anticipatory, not consummatory, anhedonia. Disagreement (i.e. score of 3 or 4) on at least three items is defined as indicating clinically significant anhedonia.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
64 participants
Primary outcome timeframe
2-hours
Results posted on
2025-07-02
Participant Flow
Participant milestones
| Measure |
High CRP LPS Intervention
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
13
|
19
|
13
|
19
|
|
Overall Study
COMPLETED
|
13
|
19
|
13
|
19
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lipopolysaccharide (LPS) Challenge in Depression
Baseline characteristics by cohort
| Measure |
High CRP LPS Intervention
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Total
n=64 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
38.0 Years
STANDARD_DEVIATION 11.1 • n=39 Participants
|
30.3 Years
STANDARD_DEVIATION 10.9 • n=41 Participants
|
29.7 Years
STANDARD_DEVIATION 10.0 • n=35 Participants
|
29.6 Years
STANDARD_DEVIATION 10.0 • n=31 Participants
|
31.5 Years
STANDARD_DEVIATION 10.8 • n=146 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=39 Participants
|
14 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
13 Participants
n=31 Participants
|
47 Participants
n=146 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
6 Participants
n=31 Participants
|
17 Participants
n=146 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
2 Participants
n=146 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
3 Participants
n=146 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=146 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
2 Participants
n=31 Participants
|
8 Participants
n=146 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=39 Participants
|
15 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
12 Participants
n=31 Participants
|
43 Participants
n=146 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
3 Participants
n=31 Participants
|
6 Participants
n=146 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
2 Participants
n=146 Participants
|
|
Snaith-Hamilton Pleasure Scale
|
27.8 units on a scale
STANDARD_DEVIATION 5.4 • n=39 Participants
|
28.7 units on a scale
STANDARD_DEVIATION 6.3 • n=41 Participants
|
25.7 units on a scale
STANDARD_DEVIATION 4.6 • n=35 Participants
|
26.5 units on a scale
STANDARD_DEVIATION 7.6 • n=31 Participants
|
27.2 units on a scale
STANDARD_DEVIATION 6.2 • n=146 Participants
|
|
Temperature
|
97.7 Degrees Fahrenheit
n=39 Participants
|
97.6 Degrees Fahrenheit
n=41 Participants
|
97.3 Degrees Fahrenheit
n=35 Participants
|
97.8 Degrees Fahrenheit
n=31 Participants
|
97.7 Degrees Fahrenheit
n=146 Participants
|
|
Montgomery Asberg Depression Rating Scale
|
23.7 units on a scale
STANDARD_DEVIATION 6.5 • n=39 Participants
|
25.1 units on a scale
STANDARD_DEVIATION 5.6 • n=41 Participants
|
22.6 units on a scale
STANDARD_DEVIATION 6.4 • n=35 Participants
|
23.7 units on a scale
STANDARD_DEVIATION 5.7 • n=31 Participants
|
23.9 units on a scale
STANDARD_DEVIATION 5.9 • n=146 Participants
|
|
Interleukin 6
|
0.9 pg/mL
n=39 Participants
|
0.4 pg/mL
n=41 Participants
|
0.5 pg/mL
n=35 Participants
|
0.4 pg/mL
n=31 Participants
|
0.6 pg/mL
n=146 Participants
|
|
Interleukin 10
|
0.2 pg/mL
n=39 Participants
|
0.2 pg/mL
n=41 Participants
|
0.2 pg/mL
n=35 Participants
|
0.3 pg/mL
n=31 Participants
|
0.2 pg/mL
n=146 Participants
|
|
Tumor Necrosis Factor
|
1.8 pg/mL
n=39 Participants
|
1.6 pg/mL
n=41 Participants
|
1.6 pg/mL
n=35 Participants
|
1.5 pg/mL
n=31 Participants
|
1.6 pg/mL
n=146 Participants
|
PRIMARY outcome
Timeframe: 2-hoursThe SHAPS is a 14-item self-administered questionnaire, with each item scored from 1-4 (strongly agree through strongly disagree; range 14-56), with higher scores indicating greater anticipatory, not consummatory, anhedonia. Disagreement (i.e. score of 3 or 4) on at least three items is defined as indicating clinically significant anhedonia.
Outcome measures
| Measure |
High CRP LPS Intervention
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
|
38.4 units on a scale
Standard Deviation 11.3
|
33.2 units on a scale
Standard Deviation 8.7
|
27.2 units on a scale
Standard Deviation 5.9
|
26.2 units on a scale
Standard Deviation 7.0
|
SECONDARY outcome
Timeframe: 24 hoursClinician-administered depression rating scale with scores ranging from 0-60. Higher scores indicate more depression.
Outcome measures
| Measure |
High CRP LPS Intervention
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
|
9.7 units on a scale
Standard Deviation 4.2
|
18.6 units on a scale
Standard Deviation 8.6
|
16.0 units on a scale
Standard Deviation 9.9
|
18.0 units on a scale
Standard Deviation 8.5
|
SECONDARY outcome
Timeframe: 2-hourspro-inflammatory cytokine measured in pg/mL
Outcome measures
| Measure |
High CRP LPS Intervention
n=12 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=13 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=12 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=17 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Change in Interleukin 6 (IL-6) Protein Levels
|
116.4 pg/mL
Interval 36.2 to 586.9
|
54.0 pg/mL
Interval 20.7 to 152.8
|
0.6 pg/mL
Interval 0.6 to 1.6
|
0.5 pg/mL
Interval 0.3 to 0.6
|
SECONDARY outcome
Timeframe: 2-hoursMeasure of systemic inflammation in pg/mL
Outcome measures
| Measure |
High CRP LPS Intervention
n=11 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=13 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=11 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=17 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Change in Interleukin 10 (IL-10) Protein Levels
|
24.1 pg/mL
Interval 17.9 to 34.8
|
12.8 pg/mL
Interval 8.6 to 20.0
|
0.2 pg/mL
Interval 0.1 to 0.2
|
0.2 pg/mL
Interval 0.1 to 0.3
|
SECONDARY outcome
Timeframe: 2-hoursMeasure of systemic inflammation in pg/mL
Outcome measures
| Measure |
High CRP LPS Intervention
n=11 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=13 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=11 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=17 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Change in Tumor Necrosis Factor (TNF) Protein Levels
|
146.0 pg/mL
Interval 48.3 to 896.4
|
130.8 pg/mL
Interval 66.7 to 377.4
|
1.5 pg/mL
Interval 1.3 to 2.1
|
1.2 pg/mL
Interval 0.9 to 2.0
|
SECONDARY outcome
Timeframe: Baseline line; 2-3 hoursPopulation: Note that there was missing data for 9 participants
Percent change of bold signal in the ventral striatum between conditions p5 and p0 at t2 - % change of bold signal in ventral striatum between conditions p5 and p0 at t1. t1= baseline scan; t2= scan performed 2 hours after LPS/saline. P5= $5 reward; p0=no reward. Data only collected at 2 timepoints.
Outcome measures
| Measure |
High CRP LPS Intervention
n=12 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=12 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=18 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=13 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Percent Signal Change in Blood Oxygenation Level Dependent Signal (BOLD) of the Ventral Striatum Reward Versus No Reward Condition
|
-0.09 Percent Signal Change
Standard Deviation 0.35
|
-0.01 Percent Signal Change
Standard Deviation 0.22
|
-0.03 Percent Signal Change
Standard Deviation 0.21
|
0.01 Percent Signal Change
Standard Deviation 0.24
|
SECONDARY outcome
Timeframe: 4-hoursBody temperature measured in degrees Fahrenheit.
Outcome measures
| Measure |
High CRP LPS Intervention
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=13 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=19 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Change in Temperature
|
98.5 Degrees Fahrenheit
Interval 98.4 to 99.2
|
98.0 Degrees Fahrenheit
Interval 97.6 to 99.2
|
98.1 Degrees Fahrenheit
Interval 97.8 to 98.6
|
98.0 Degrees Fahrenheit
Interval 97.8 to 98.6
|
SECONDARY outcome
Timeframe: Baseline line 2-3 hoursPopulation: Note that there was missing data for 9 participants
Percent change of bold signal in the insula between exteroceptive and interoceptive conditions at t2 - % change of bold signal in insula between exteroceptive and interoceptive conditions at t1. t1= baseline scan; t2= scan performed 2 hours after LPS/saline. Data only collected at 2 timepoints.
Outcome measures
| Measure |
High CRP LPS Intervention
n=12 Participants
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=12 Participants
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=18 Participants
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=13 Participants
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Percent Signal Change in Blood Oxygenation Level Dependent Signal (BOLD) of the Insula (Interoceptive vs Exteroceptive Condition)
|
0.01 Percent Signal Change
Standard Deviation 0.10
|
-0.06 Percent Signal Change
Standard Deviation 0.15
|
0.01 Percent Signal Change
Standard Deviation 0.14
|
-0.10 Percent Signal Change
Standard Deviation 0.17
|
Adverse Events
High CRP LPS Intervention
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Low CRP LPS Intervention
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
High CRP LPS Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Low CRP LPS Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
High CRP LPS Intervention
n=13 participants at risk
High CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
Low CRP LPS Intervention
n=19 participants at risk
Low CRP Individuals with Major Depressive Disorder receiving LPS intervention
Lipopolysaccharide: Lipopolysaccharide (LPS) derived from E. Coli group O 113:H10:K negative
|
High CRP LPS Placebo
n=13 participants at risk
High CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
Low CRP LPS Placebo
n=19 participants at risk
Low CRP Individuals with Major Depressive Disorder receiving placebo
Placebo: Saline solution
|
|---|---|---|---|---|
|
Psychiatric disorders
Anxiety
|
0.00%
0/13 • One week
|
5.3%
1/19 • One week
|
0.00%
0/13 • One week
|
0.00%
0/19 • One week
|
|
General disorders
Vasovagal Reaction
|
0.00%
0/13 • One week
|
0.00%
0/19 • One week
|
0.00%
0/13 • One week
|
5.3%
1/19 • One week
|
|
Gastrointestinal disorders
Nausea
|
15.4%
2/13 • One week
|
0.00%
0/19 • One week
|
0.00%
0/13 • One week
|
0.00%
0/19 • One week
|
|
General disorders
Fever
|
7.7%
1/13 • One week
|
0.00%
0/19 • One week
|
0.00%
0/13 • One week
|
0.00%
0/19 • One week
|
|
Infections and infestations
UTI
|
0.00%
0/13 • One week
|
5.3%
1/19 • One week
|
0.00%
0/13 • One week
|
0.00%
0/19 • One week
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place