Depression
Conditions
Brief summary
Depression is very common and poses a huge disease burden. About 20% of the US population suffers from depression at lease once in their lifetime. Inflammations that are hidden inside our body as a result of aging, obesity, chronic diseases, or certain treatments (e.g., interferon for hepatitis C) appear to cause depressive symptoms and even clinical depression. Individuals with such inflammations are more likely to suffer from depression and are less likely to respond to currently available antidepressant medications. This study will test leucine, an amino acid, as a new way to mitigate depressive symptoms in response to such inflammations. This study begins with a 90-minute screening session to determine whether participants are eligible to join the main study. Those who meet the eligibility criteria will then join the main study, which will consist of taking leucine or maltodextrin (i.e., oral placebo) for 2 weeks at home and an 8-hour session at the UCLA Medical Center. A brief telephone follow-up every 3 months for 2 years with questions on mood is also planned. Approximately 90 healthy adults will be recruited for participation in the study. During the course of the study, participants will take leucine or maltodextrin for 2 weeks at home and then will be injected either lipopolysaccharide (LPS) or saline (i.e., intravenous placebo) at the UCLA Medical Center. LPS is a bacterial substance that can initiate chemical reactions that are similar to those seen in individuals with mild sickness symptoms, such as a slight increase in body temperature, muscle aches, or tiredness. It is a safe way of investigating the body's response to inflammation and how these changes may alter cognitive, emotional, or neural function. It has been given thousands of times to healthy volunteers - both younger and older adults - without any serious side effects.
Interventions
DIETARY_SUPPLEMENTleucine
amino acid leucine in powder
OTHERPO placebo
maltodextrin
BIOLOGICALlipopolysaccharide (LPS)
purified bacterial wall component as an inflammatory challenge
OTHERIV placebo
0.9% saline
Sponsors
National Institute of Mental Health (NIMH)
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Participants will be required to be in good general health (as evaluated during the phone and in-person screening sessions) and aged 18 to 65 years.
Exclusion criteria
Following a structured telephone interview, prospective participants with the following conditions will not advance to the in-person screening session: presence of chronic mental or physical illness, history of allergies, autoimmune, liver, or other severe chronic diseases, current use of prescription medications such as steroids, NSAIDs, immune modifying drugs, opioid analgesics, and psychotropics, or previous history of fainting during blood draws. These inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Depressed Mood From Baseline | At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration | Depression Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 32; higher values represent worse outcome, i.e., more severe depressed mood; the absolute values at each time point are presented here rather than change of values between time points; zero (0) in mean and standard deviation reflect measured data and not placeholder values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Feelings of Social Disconnection From Baseline | At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration | Feelings of Social Disconnection Scale: a self-report questionnaire of feelings of social disconnection with scores ranging from 0 to 28, with higher scores indicating more severe feelings of social disconnection. |
| Change in Fatigue From Baseline | At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration | Fatigue Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 20; higher values represent worse outcome, i.e., more severe fatigue; the absolute values at each time point are presented here rather than change of values between time points. |
| Change in Depressive Symptoms From Baseline | At baseline and then at 2 and 4 hours after LPS (or saline) administration | Montgomery-Asberg Depression Rating Scale (MADRS): a clinician-rated questionnaire of depressive symptoms with scores ranging from 0 to 60, with higher scores indicating more severe depressive symptoms. |
| Change in Memory Domains of Cognitive Function From Baseline | At baseline and then 3 hours after LPS (or saline) administration | Memory domains of cognitive function were measured using the computerized tests from CNS Vital Signs™: verbal memory using Verbal Memory Test (total scores ranging from 0 to 60; higher scores mean a better outcome); and visual memory using Visual Memory Test (total scores ranging from 0 to 60; higher scores mean a better outcome). The absolute values at each time point are presented. |
| Change in Non-memory Domains of Cognitive Function From Baseline | At baseline and then 3 hours after LPS (or saline) administration | Non-memory domains of cognitive function were measured using the computerized tests from CNS Vital Signs™: executive function using Stroop Test (average reaction time in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome); and attention using Shifting Attention Test (average reaction time for correct responses in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome) and Continuous Performance Test (average reaction time for correct responses in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome). The absolute values at each time point are presented. |
| Change in Confusion From Baseline | At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration | Confusion Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 20; higher values represent worse outcome, i.e., more severe confusion; the absolute values at each time point are presented here rather than change of values between time points; zero (0) in mean and standard deviation reflect measured data and not placeholder values. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Anhedonia | 2 hours after LPS (or saline) administration | Facial expressions and skin conductance in response to funny film clips using the iMotions®Attention Tool (iMotions Inc., Cambridge, MA) which performs automatic analysis of facial expressions from video and integrates simultaneous measurement of skin conductance |
| Change in Gene Expression From Baseline | At baseline and 30 minutes after LPS (or saline) administration | Genome-wide transcriptional profiling conducted using Illumina HT-12 BeadArrays |
| Subjective Sensitivity to Social Rejection | 2 hours after LPS (or saline) administration | Using the Cyberball Social Exclusion Task, feelings of social distress to social rejection are evaluated based on a scale with the total score ranging from 0 to 48; higher values represent worse outcome, i.e., more severe social distress. The Overall Number of Participants Analyzed is different from numbers of participants reported in the Participant Flow module because some participants declined to complete this task. |
| Negative Bias in Facial Emotion Recognition | 2 hours after LPS (or saline) administration | Emotional Face Recognition Task consists in showing participants a series of black and white photographs (Ekman Pictures of facial affect), in which the facial expression is morphed from neutral to either Sad, Angry, or Happy. For each image, participants will be asked to make a forced choice about the emotion expressed, and rate their certainty. |
| Subjective Sensitivity to Social Acceptance | 2 hours after drug administration | Prior to the experimental session, participants are asked to complete a survey that contains several personality questionnaires and are video-recorded for 2-5 minutes as they discuss what they like about themselves. Participants are told that 8 people will form impressions of them by selecting personality traits to describe them. Participants then see a photograph of themselves along with a descriptive word underneath (supposedly provided by the evaluators), which is pre-rated based on desirability, and are asked to rate subjective happiness when each of the feedback items is presented. The total score of the scale ranges from 0 to 105; higher values represent better outcome, i.e., higher social reward. The Overall Number of Participants Analyzed is different from numbers of participants reported in the Participant Flow module because some participants declined to complete this task. |
| Reward | 2 hours after LPS (or saline) administration | Reward Learning Task (a laboratory based probabilistic reward task that objectively measures participants' ability to modulate behavior as a function of reward) |
| Change in Proinflammatory Cytokines From Baseline | At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration | Plasma proinflammatory cytokines (interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, and soluble tumor necrosis factor receptor) |
| Change in Kynurenine Metabolites From Baseline | At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration | Plasma tryptophan, kynurenine, quinolinic acid, and kynurenic acid |
Countries
United States
Participant flow
Pre-assignment details
A total of 88 subjects were interviewed, 73 eligible, and 70 randomized. Out of these 70, 11 did not participate in the actual study (7 declined; 3 tested positive in urine toxicology on the study day, which was a pre-set exclusion criterion; 1 reported using a drug given by another study on the study day). Thus, 59 were enrolled in and started the study, an experimental provocation trial involving LPS injection, which was a necessary step for a participant to be considered enrolled and started.
Participants by arm
| Arm | Count |
|---|---|
| PO Leucine & IV LPS Oral (PO) leucine 6 g twice a day for 2 weeks followed by a single intravenous (IV) bolus of lipopolysaccharide (LPS) 0.8 ng/kg of body weight
leucine: amino acid leucine in powder
lipopolysaccharide (LPS): purified bacterial wall component as an inflammatory challenge | 23 |
| PO Placebo & IV LPS PO maltodextrin (placebo) twice a day for 2 weeks followed by a single IV bolus of LPS 0.8 ng/kg of body weight
PO placebo: maltodextrin
lipopolysaccharide (LPS): purified bacterial wall component as an inflammatory challenge | 18 |
| PO Leucine & IV Placebo PO leucine 6 g twice a day for 2 weeks followed by a single IV bolus of 0.9% saline
leucine: amino acid leucine in powder
IV placebo: 0.9% saline | 8 |
| PO Placebo & IV Placebo PO maltodextrin (placebo) twice a day for 2 weeks followed by a single IV bolus of 0.9% saline
PO placebo: maltodextrin
IV placebo: 0.9% saline | 10 |
| Total | 59 |
Baseline characteristics
| Characteristic | PO Leucine & IV LPS | PO Placebo & IV LPS | PO Leucine & IV Placebo | PO Placebo & IV Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 16.3 | 26.8 years STANDARD_DEVIATION 12.7 | 33.1 years STANDARD_DEVIATION 12.6 | 31.9 years STANDARD_DEVIATION 14.9 | 31.8 years STANDARD_DEVIATION 14.6 |
| Body-mass index | 24.3 kg/m^2 STANDARD_DEVIATION 4 | 23.6 kg/m^2 STANDARD_DEVIATION 3 | 26.3 kg/m^2 STANDARD_DEVIATION 2.9 | 25.5 kg/m^2 STANDARD_DEVIATION 4 | 24.6 kg/m^2 STANDARD_DEVIATION 3.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 17 Participants | 6 Participants | 9 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 9 Participants | 1 Participants | 3 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 10 Participants | 8 Participants | 6 Participants | 7 Participants | 31 Participants |
| Region of Enrollment United States | 23 participants | 18 participants | 8 participants | 10 participants | 59 participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 2 Participants | 4 Participants | 24 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 6 Participants | 6 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 18 | 0 / 8 | 0 / 10 |
| other Total, other adverse events | 0 / 23 | 0 / 18 | 0 / 8 | 0 / 10 |
| serious Total, serious adverse events | 0 / 23 | 0 / 18 | 0 / 8 | 0 / 10 |
Outcome results
Primary
Change in Depressed Mood From Baseline
Depression Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 32; higher values represent worse outcome, i.e., more severe depressed mood; the absolute values at each time point are presented here rather than change of values between time points; zero (0) in mean and standard deviation reflect measured data and not placeholder values.
Time frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | Baseline | .6818182 score on a scale | Standard Deviation 1.86155 |
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | 3 hours | .5909091 score on a scale | Standard Deviation 2.363595 |
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | 1 hour | 1.619048 score on a scale | Standard Deviation 3.879126 |
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | 4 hours | .4285714 score on a scale | Standard Deviation 1.963961 |
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | 1.5 hours | 1.55 score on a scale | Standard Deviation 3.817894 |
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | 6 hours | .5238095 score on a scale | Standard Deviation 2.182179 |
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | 2 hours | 1 score on a scale | Standard Deviation 3.829708 |
| PO Leucine & IV LPS | Change in Depressed Mood From Baseline | 5 hours | .4545455 score on a scale | Standard Deviation 2.132007 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | Baseline | .5294118 score on a scale | Standard Deviation 1.178858 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | 6 hours | 0 score on a scale | Standard Deviation 0 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | 3 hours | .5625 score on a scale | Standard Deviation 1.364734 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | 5 hours | .0555556 score on a scale | Standard Deviation 0.2357023 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | 1.5 hours | 1 score on a scale | Standard Deviation 2.371708 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | 2 hours | 1.111111 score on a scale | Standard Deviation 3.103866 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | 4 hours | .3333333 score on a scale | Standard Deviation 0.9701425 |
| PO Placebo & IV LPS | Change in Depressed Mood From Baseline | 1 hour | .7647059 score on a scale | Standard Deviation 1.480262 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | 4 hours | .1428571 score on a scale | Standard Deviation 0.3779645 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | 5 hours | .1666667 score on a scale | Standard Deviation 0.4082483 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | 6 hours | .1428571 score on a scale | Standard Deviation 0.3779645 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | 1 hour | .375 score on a scale | Standard Deviation 0.7440238 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | 1.5 hours | .25 score on a scale | Standard Deviation 0.46291 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | Baseline | .2857143 score on a scale | Standard Deviation 0.48795 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | 2 hours | .7142857 score on a scale | Standard Deviation 1.253566 |
| PO Leucine & IV Placebo | Change in Depressed Mood From Baseline | 3 hours | .375 score on a scale | Standard Deviation 1.06066 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | 6 hours | 0 score on a scale | Standard Deviation 0 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | Baseline | .6 score on a scale | Standard Deviation 1.074968 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | 1 hour | 0 score on a scale | Standard Deviation 0 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | 1.5 hours | .1 score on a scale | Standard Deviation 0.3162278 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | 2 hours | .4 score on a scale | Standard Deviation 0.6992059 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | 3 hours | .1111111 score on a scale | Standard Deviation 0.3333333 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | 4 hours | 0 score on a scale | Standard Deviation 0 |
| PO Placebo & IV Placebo | Change in Depressed Mood From Baseline | 5 hours | 0 score on a scale | Standard Deviation 0 |
Secondary
Change in Confusion From Baseline
Confusion Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 20; higher values represent worse outcome, i.e., more severe confusion; the absolute values at each time point are presented here rather than change of values between time points; zero (0) in mean and standard deviation reflect measured data and not placeholder values.
Time frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PO Leucine & IV LPS | Change in Confusion From Baseline | Baseline | 1.409091 score on a scale | Standard Deviation 1.991867 |
| PO Leucine & IV LPS | Change in Confusion From Baseline | 1 hours | 2.238095 score on a scale | Standard Deviation 3.845839 |
| PO Leucine & IV LPS | Change in Confusion From Baseline | 1.5 hours | 2.095238 score on a scale | Standard Deviation 3.462727 |
| PO Leucine & IV LPS | Change in Confusion From Baseline | 2 hours | 1.772727 score on a scale | Standard Deviation 3.435554 |
| PO Leucine & IV LPS | Change in Confusion From Baseline | 3 hours | 1.454545 score on a scale | Standard Deviation 2.063914 |
| PO Leucine & IV LPS | Change in Confusion From Baseline | 4 hours | .6363636 score on a scale | Standard Deviation 1.216766 |
| PO Leucine & IV LPS | Change in Confusion From Baseline | 5 hours | .6363636 score on a scale | Standard Deviation 1.398824 |
| PO Leucine & IV LPS | Change in Confusion From Baseline | 6 hours | .4761905 score on a scale | Standard Deviation 1.435933 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | 4 hours | .6111111 score on a scale | Standard Deviation 1.195033 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | 3 hours | .8888889 score on a scale | Standard Deviation 1.131833 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | 1 hours | .8888889 score on a scale | Standard Deviation 1.07861 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | 6 hours | .4705882 score on a scale | Standard Deviation 1.06757 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | 5 hours | .6111111 score on a scale | Standard Deviation 1.036901 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | 2 hours | 1.111111 score on a scale | Standard Deviation 1.323493 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | 1.5 hours | 1.222222 score on a scale | Standard Deviation 1.308594 |
| PO Placebo & IV LPS | Change in Confusion From Baseline | Baseline | 1.125 score on a scale | Standard Deviation 1.408309 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | 5 hours | .5 score on a scale | Standard Deviation 0.5773503 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | 1.5 hours | .375 score on a scale | Standard Deviation 1.06066 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | 2 hours | .625 score on a scale | Standard Deviation 1.407886 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | 3 hours | .625 score on a scale | Standard Deviation 1.06066 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | 4 hours | .5714286 score on a scale | Standard Deviation 1.133893 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | 6 hours | .1428571 score on a scale | Standard Deviation 0.3779645 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | Baseline | 1 score on a scale | Standard Deviation 1.825742 |
| PO Leucine & IV Placebo | Change in Confusion From Baseline | 1 hours | 1 score on a scale | Standard Deviation 1.414214 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | 1.5 hours | .1 score on a scale | Standard Deviation 0.3162278 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | 2 hours | .1 score on a scale | Standard Deviation 0.3162278 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | 1 hours | .4444444 score on a scale | Standard Deviation 1.013794 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | Baseline | 1.1 score on a scale | Standard Deviation 1.286684 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | 3 hours | .3333333 score on a scale | Standard Deviation 0.7071068 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | 6 hours | 0 score on a scale | Standard Deviation 0 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | 5 hours | .1 score on a scale | Standard Deviation 0.3162278 |
| PO Placebo & IV Placebo | Change in Confusion From Baseline | 4 hours | 0 score on a scale | Standard Deviation 0 |
Secondary
Change in Depressive Symptoms From Baseline
Montgomery-Asberg Depression Rating Scale (MADRS): a clinician-rated questionnaire of depressive symptoms with scores ranging from 0 to 60, with higher scores indicating more severe depressive symptoms.
Time frame: At baseline and then at 2 and 4 hours after LPS (or saline) administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PO Leucine & IV LPS | Change in Depressive Symptoms From Baseline | Baseline | 2.086957 score on a scale | Standard Deviation 2.574579 |
| PO Leucine & IV LPS | Change in Depressive Symptoms From Baseline | 4 hours | 1.045455 score on a scale | Standard Deviation 1.812057 |
| PO Leucine & IV LPS | Change in Depressive Symptoms From Baseline | 2 hours | 3 score on a scale | Standard Deviation 5.485913 |
| PO Placebo & IV LPS | Change in Depressive Symptoms From Baseline | Baseline | 2.125 score on a scale | Standard Deviation 3.052322 |
| PO Placebo & IV LPS | Change in Depressive Symptoms From Baseline | 4 hours | 1.529412 score on a scale | Standard Deviation 1.907801 |
| PO Placebo & IV LPS | Change in Depressive Symptoms From Baseline | 2 hours | 4 score on a scale | Standard Deviation 6.184658 |
| PO Leucine & IV Placebo | Change in Depressive Symptoms From Baseline | 2 hours | 1.875 score on a scale | Standard Deviation 2.295181 |
| PO Leucine & IV Placebo | Change in Depressive Symptoms From Baseline | Baseline | 2.5 score on a scale | Standard Deviation 3.891382 |
| PO Leucine & IV Placebo | Change in Depressive Symptoms From Baseline | 4 hours | 2.142857 score on a scale | Standard Deviation 1.864454 |
| PO Placebo & IV Placebo | Change in Depressive Symptoms From Baseline | Baseline | 1.222222 score on a scale | Standard Deviation 1.301708 |
| PO Placebo & IV Placebo | Change in Depressive Symptoms From Baseline | 4 hours | .2 score on a scale | Standard Deviation 0.421637 |
| PO Placebo & IV Placebo | Change in Depressive Symptoms From Baseline | 2 hours | .7 score on a scale | Standard Deviation 0.9486833 |
Secondary
Change in Fatigue From Baseline
Fatigue Subscale of the Short Form of the Profile of Mood States (POMS-SF): total score ranges from 0 to 20; higher values represent worse outcome, i.e., more severe fatigue; the absolute values at each time point are presented here rather than change of values between time points.
Time frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PO Leucine & IV LPS | Change in Fatigue From Baseline | Baseline | 2.409091 score on a scale | Standard Deviation 2.839502 |
| PO Leucine & IV LPS | Change in Fatigue From Baseline | 1 hours | 3.666667 score on a scale | Standard Deviation 4.09064 |
| PO Leucine & IV LPS | Change in Fatigue From Baseline | 1.5 hours | 5.095238 score on a scale | Standard Deviation 5.290603 |
| PO Leucine & IV LPS | Change in Fatigue From Baseline | 2 hours | 4.681818 score on a scale | Standard Deviation 5.083928 |
| PO Leucine & IV LPS | Change in Fatigue From Baseline | 3 hours | 4.590909 score on a scale | Standard Deviation 4.584229 |
| PO Leucine & IV LPS | Change in Fatigue From Baseline | 4 hours | 3.272727 score on a scale | Standard Deviation 4.322497 |
| PO Leucine & IV LPS | Change in Fatigue From Baseline | 5 hours | 3.454545 score on a scale | Standard Deviation 4.925418 |
| PO Leucine & IV LPS | Change in Fatigue From Baseline | 6 hours | 2.666667 score on a scale | Standard Deviation 4.564355 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | 4 hours | 2.111111 score on a scale | Standard Deviation 2.246275 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | 3 hours | 3.555556 score on a scale | Standard Deviation 3.014128 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | 1 hours | 3.611111 score on a scale | Standard Deviation 3.310214 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | 6 hours | 1.944444 score on a scale | Standard Deviation 2.508157 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | 5 hours | 2.222222 score on a scale | Standard Deviation 2.438793 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | 2 hours | 4.333333 score on a scale | Standard Deviation 3.694193 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | 1.5 hours | 4.444444 score on a scale | Standard Deviation 2.994548 |
| PO Placebo & IV LPS | Change in Fatigue From Baseline | Baseline | 2.117647 score on a scale | Standard Deviation 2.027386 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | 5 hours | 2.833333 score on a scale | Standard Deviation 4.167333 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | 1.5 hours | 2.25 score on a scale | Standard Deviation 4.399675 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | 2 hours | 2.375 score on a scale | Standard Deviation 3.73927 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | 3 hours | 2.625 score on a scale | Standard Deviation 4.10357 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | 4 hours | 2.571429 score on a scale | Standard Deviation 4.197505 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | 6 hours | 1.571429 score on a scale | Standard Deviation 2.935821 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | Baseline | 1.857143 score on a scale | Standard Deviation 3.338092 |
| PO Leucine & IV Placebo | Change in Fatigue From Baseline | 1 hours | 2.25 score on a scale | Standard Deviation 3.412163 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | 1.5 hours | 1 score on a scale | Standard Deviation 1.247219 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | 2 hours | .9 score on a scale | Standard Deviation 1.449138 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | 1 hours | .6666667 score on a scale | Standard Deviation 0.8660254 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | Baseline | 2 score on a scale | Standard Deviation 1.885618 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | 3 hours | 1.777778 score on a scale | Standard Deviation 1.855921 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | 6 hours | 1 score on a scale | Standard Deviation 1.581139 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | 5 hours | 1.3 score on a scale | Standard Deviation 1.946507 |
| PO Placebo & IV Placebo | Change in Fatigue From Baseline | 4 hours | .6 score on a scale | Standard Deviation 1.074968 |
Secondary
Change in Feelings of Social Disconnection From Baseline
Feelings of Social Disconnection Scale: a self-report questionnaire of feelings of social disconnection with scores ranging from 0 to 28, with higher scores indicating more severe feelings of social disconnection.
Time frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | Baseline | 22.52381 score on a scale | Standard Deviation 7.639496 |
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | 1 hour | 16.65217 score on a scale | Standard Deviation 7.327462 |
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | 1.5 hours | 16.86364 score on a scale | Standard Deviation 7.942025 |
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | 2 hours | 15.33333 score on a scale | Standard Deviation 7.308335 |
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | 3 hours | 15.38095 score on a scale | Standard Deviation 6.6744 |
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | 4 hours | 15.71429 score on a scale | Standard Deviation 7.26046 |
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | 5 hours | 16.28571 score on a scale | Standard Deviation 7.444077 |
| PO Leucine & IV LPS | Change in Feelings of Social Disconnection From Baseline | 6 hours | 16.25 score on a scale | Standard Deviation 7.27559 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | 4 hours | 16.66667 score on a scale | Standard Deviation 9.749811 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | 3 hours | 15.8125 score on a scale | Standard Deviation 9.914426 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | 1 hour | 17.83333 score on a scale | Standard Deviation 9.463552 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | 6 hours | 17.72222 score on a scale | Standard Deviation 8.68945 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | 5 hours | 19.38889 score on a scale | Standard Deviation 13.3775 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | 2 hours | 17.05556 score on a scale | Standard Deviation 9.276613 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | 1.5 hours | 16.77778 score on a scale | Standard Deviation 9.42809 |
| PO Placebo & IV LPS | Change in Feelings of Social Disconnection From Baseline | Baseline | 24 score on a scale | Standard Deviation 8.581786 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 5 hours | 19.5 score on a scale | Standard Deviation 10.96814 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 1.5 hours | 17.125 score on a scale | Standard Deviation 6.220645 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 2 hours | 17 score on a scale | Standard Deviation 6.546537 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 3 hours | 18 score on a scale | Standard Deviation 5.744563 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 4 hours | 16.42857 score on a scale | Standard Deviation 6.803361 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 6 hours | 14.57143 score on a scale | Standard Deviation 7.807201 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | Baseline | 22.57143 score on a scale | Standard Deviation 6.704654 |
| PO Leucine & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 1 hour | 18 score on a scale | Standard Deviation 6.21059 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 1.5 hours | 13.625 score on a scale | Standard Deviation 7.836499 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 2 hours | 18.3 score on a scale | Standard Deviation 14.95215 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 1 hour | 15.44444 score on a scale | Standard Deviation 12.26898 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | Baseline | 21.6 score on a scale | Standard Deviation 10.7827 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 3 hours | 13.55556 score on a scale | Standard Deviation 9.166667 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 6 hours | 19.9 score on a scale | Standard Deviation 18.62167 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 5 hours | 17.6 score on a scale | Standard Deviation 14.19859 |
| PO Placebo & IV Placebo | Change in Feelings of Social Disconnection From Baseline | 4 hours | 19.6 score on a scale | Standard Deviation 19.65932 |
Secondary
Change in Memory Domains of Cognitive Function From Baseline
Memory domains of cognitive function were measured using the computerized tests from CNS Vital Signs™: verbal memory using Verbal Memory Test (total scores ranging from 0 to 60; higher scores mean a better outcome); and visual memory using Visual Memory Test (total scores ranging from 0 to 60; higher scores mean a better outcome). The absolute values at each time point are presented.
Time frame: At baseline and then 3 hours after LPS (or saline) administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PO Leucine & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory baseline | 51.30435 score on a scale | Standard Deviation 8.298054 |
| PO Leucine & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory 3 hours | 48.66667 score on a scale | Standard Deviation 5.695027 |
| PO Leucine & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Visual memory baseline | 44.04348 score on a scale | Standard Deviation 6.588408 |
| PO Leucine & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Visual memory 3 hours | 42.2381 score on a scale | Standard Deviation 6.106593 |
| PO Placebo & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory 3 hours | 52.58824 score on a scale | Standard Deviation 6.538911 |
| PO Placebo & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Visual memory baseline | 47.76471 score on a scale | Standard Deviation 5.695716 |
| PO Placebo & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Visual memory 3 hours | 46.29412 score on a scale | Standard Deviation 7.405781 |
| PO Placebo & IV LPS | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory baseline | 53.23529 score on a scale | Standard Deviation 6.139314 |
| PO Leucine & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Visual memory baseline | 46.125 score on a scale | Standard Deviation 6.490377 |
| PO Leucine & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory 3 hours | 48.5 score on a scale | Standard Deviation 5.976143 |
| PO Leucine & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Visual memory 3 hours | 41.75 score on a scale | Standard Deviation 4.26782 |
| PO Leucine & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory baseline | 51.125 score on a scale | Standard Deviation 4.580627 |
| PO Placebo & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Visual memory 3 hours | 40.9 score on a scale | Standard Deviation 9.097619 |
| PO Placebo & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory 3 hours | 45.5 score on a scale | Standard Deviation 10.31988 |
| PO Placebo & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Verbal memory baseline | 52.3 score on a scale | Standard Deviation 8.525126 |
| PO Placebo & IV Placebo | Change in Memory Domains of Cognitive Function From Baseline | Visual memory baseline | 43.9 score on a scale | Standard Deviation 8.736259 |
Secondary
Change in Non-memory Domains of Cognitive Function From Baseline
Non-memory domains of cognitive function were measured using the computerized tests from CNS Vital Signs™: executive function using Stroop Test (average reaction time in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome); and attention using Shifting Attention Test (average reaction time for correct responses in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome) and Continuous Performance Test (average reaction time for correct responses in milliseconds thus ranging from 0 to infinite; shorter reaction time means a better outcome). The absolute values at each time point are presented.
Time frame: At baseline and then 3 hours after LPS (or saline) administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PO Leucine & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test baseline | 356.913 milliseconds | Standard Deviation 95.80563 |
| PO Leucine & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test 3 hours | 386.2381 milliseconds | Standard Deviation 93.90842 |
| PO Leucine & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention baseline | 1014.174 milliseconds | Standard Deviation 199.4204 |
| PO Leucine & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention 3 hours | 957.2857 milliseconds | Standard Deviation 211.8759 |
| PO Leucine & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance baseline | 449.1304 milliseconds | Standard Deviation 73.88954 |
| PO Leucine & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance 3 hours | 456.619 milliseconds | Standard Deviation 65.31422 |
| PO Placebo & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance 3 hours | 423.8235 milliseconds | Standard Deviation 54.88993 |
| PO Placebo & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention 3 hours | 829.7647 milliseconds | Standard Deviation 131.7823 |
| PO Placebo & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test baseline | 307.6471 milliseconds | Standard Deviation 57.51515 |
| PO Placebo & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention baseline | 899.6471 milliseconds | Standard Deviation 140.7502 |
| PO Placebo & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test 3 hours | 316.2353 milliseconds | Standard Deviation 53.88475 |
| PO Placebo & IV LPS | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance baseline | 426 milliseconds | Standard Deviation 44.63743 |
| PO Leucine & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test 3 hours | 324.25 milliseconds | Standard Deviation 36.86946 |
| PO Leucine & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention baseline | 935.75 milliseconds | Standard Deviation 185.7423 |
| PO Leucine & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention 3 hours | 943 milliseconds | Standard Deviation 109.6696 |
| PO Leucine & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance 3 hours | 439.25 milliseconds | Standard Deviation 35.05812 |
| PO Leucine & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance baseline | 442.25 milliseconds | Standard Deviation 27.41089 |
| PO Leucine & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test baseline | 304.125 milliseconds | Standard Deviation 38.96679 |
| PO Placebo & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance baseline | 458.2 milliseconds | Standard Deviation 44.96122 |
| PO Placebo & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Continuous performance 3 hours | 460.6 milliseconds | Standard Deviation 55.05795 |
| PO Placebo & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test 3 hours | 337.4 milliseconds | Standard Deviation 45.80442 |
| PO Placebo & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention 3 hours | 957.5 milliseconds | Standard Deviation 156.2358 |
| PO Placebo & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Stroop test baseline | 268.8 milliseconds | Standard Deviation 146.5619 |
| PO Placebo & IV Placebo | Change in Non-memory Domains of Cognitive Function From Baseline | Shifting attention baseline | 947.9 milliseconds | Standard Deviation 140.4457 |
Other Pre-specified
Anhedonia
Facial expressions and skin conductance in response to funny film clips using the iMotions®Attention Tool (iMotions Inc., Cambridge, MA) which performs automatic analysis of facial expressions from video and integrates simultaneous measurement of skin conductance
Time frame: 2 hours after LPS (or saline) administration
Population: The study was paused during the COVID pandemic because endotoxin, a biologic derived from an infectious agent, was being used. Then, the request for COIVD supplement to NIMH was denied, and due to the lack of funds, the study was prematurely terminated. As the raw data of this particular outcome measure consist in recordings of facial expression and skin conductance, further processing by a specialized technician and additional funds are required. Thus we are currently unable to report the data.
Other Pre-specified
Change in Gene Expression From Baseline
Genome-wide transcriptional profiling conducted using Illumina HT-12 BeadArrays
Time frame: At baseline and 30 minutes after LPS (or saline) administration
Population: The study was paused during the COVID pandemic because endotoxin, a biologic derived from an infectious agent, was being used. Then, the request for COIVD supplement to NIMH was denied, and due to the lack of funds, the study was prematurely terminated. Due to the lack of funds, the blood sample could not be assayed, and we are currently unable to report the data for this particular outcome measure.
Other Pre-specified
Change in Kynurenine Metabolites From Baseline
Plasma tryptophan, kynurenine, quinolinic acid, and kynurenic acid
Time frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Population: The study was paused during the COVID pandemic because endotoxin, a biologic derived from an infectious agent, was being used. Then, the request for COIVD supplement to NIMH was denied, and due to the lack of funds, the study was prematurely terminated. Due to the lack of funds, the blood sample could not be assayed, and we are currently unable to report the data for this particular outcome measure.
Other Pre-specified
Change in Proinflammatory Cytokines From Baseline
Plasma proinflammatory cytokines (interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, and soluble tumor necrosis factor receptor)
Time frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Population: The study was paused during the COVID pandemic because endotoxin, a biologic derived from an infectious agent, was being used. Then, the request for COIVD supplement to NIMH was denied, and due to the lack of funds, the study was prematurely terminated. As the raw data of this particular outcome measure require further processing and thus further funds, we are currently unable to process and report the data.
Other Pre-specified
Negative Bias in Facial Emotion Recognition
Emotional Face Recognition Task consists in showing participants a series of black and white photographs (Ekman Pictures of facial affect), in which the facial expression is morphed from neutral to either Sad, Angry, or Happy. For each image, participants will be asked to make a forced choice about the emotion expressed, and rate their certainty.
Time frame: 2 hours after LPS (or saline) administration
Population: The study was paused during the COVID pandemic because endotoxin, a biologic derived from an infectious agent, was being used. Then, the request for COIVD supplement to NIMH was denied, and due to the lack of funds, the study was prematurely terminated. As the raw data of this particular outcome measure require further processing by a specialized technician and thus additional funds, we are currently unable to process and report the data.
Other Pre-specified
Reward
Reward Learning Task (a laboratory based probabilistic reward task that objectively measures participants' ability to modulate behavior as a function of reward)
Time frame: 2 hours after LPS (or saline) administration
Population: The study was paused during the COVID pandemic because endotoxin, a biologic derived from an infectious agent, was being used. Then, the request for COIVD supplement to NIMH was denied, and due to the lack of funds, the study was prematurely terminated. As the raw data of this particular outcome measure require further processing by a specialized technician and thus additional funds, we are currently unable to process and report the data.
Other Pre-specified
Subjective Sensitivity to Social Acceptance
Prior to the experimental session, participants are asked to complete a survey that contains several personality questionnaires and are video-recorded for 2-5 minutes as they discuss what they like about themselves. Participants are told that 8 people will form impressions of them by selecting personality traits to describe them. Participants then see a photograph of themselves along with a descriptive word underneath (supposedly provided by the evaluators), which is pre-rated based on desirability, and are asked to rate subjective happiness when each of the feedback items is presented. The total score of the scale ranges from 0 to 105; higher values represent better outcome, i.e., higher social reward. The Overall Number of Participants Analyzed is different from numbers of participants reported in the Participant Flow module because some participants declined to complete this task.
Time frame: 2 hours after drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PO Leucine & IV LPS | Subjective Sensitivity to Social Acceptance | 76.7619 score on a scale | Standard Deviation 9.229869 |
| PO Placebo & IV LPS | Subjective Sensitivity to Social Acceptance | 77.38889 score on a scale | Standard Deviation 5.94226 |
| PO Leucine & IV Placebo | Subjective Sensitivity to Social Acceptance | 76.28571 score on a scale | Standard Deviation 3.77334 |
| PO Placebo & IV Placebo | Subjective Sensitivity to Social Acceptance | 78.3 score on a scale | Standard Deviation 6.037844 |
Other Pre-specified
Subjective Sensitivity to Social Rejection
Using the Cyberball Social Exclusion Task, feelings of social distress to social rejection are evaluated based on a scale with the total score ranging from 0 to 48; higher values represent worse outcome, i.e., more severe social distress. The Overall Number of Participants Analyzed is different from numbers of participants reported in the Participant Flow module because some participants declined to complete this task.
Time frame: 2 hours after LPS (or saline) administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PO Leucine & IV LPS | Subjective Sensitivity to Social Rejection | 18.05 score on a scale | Standard Deviation 5.670561 |
| PO Placebo & IV LPS | Subjective Sensitivity to Social Rejection | 16.17647 score on a scale | Standard Deviation 5.282463 |
| PO Leucine & IV Placebo | Subjective Sensitivity to Social Rejection | 18.25 score on a scale | Standard Deviation 7.245688 |
| PO Placebo & IV Placebo | Subjective Sensitivity to Social Rejection | 17.6 score on a scale | Standard Deviation 5.481281 |