Trial Outcomes & Findings for Leucine for Depression Study (L-DEP) (NCT NCT03557684)
NCT ID: NCT03557684
Last Updated: 2023-06-08
Results Overview
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.
TERMINATED
EARLY_PHASE1
59 participants
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
2023-06-08
Participant Flow
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.
Participant milestones
| Measure |
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
|
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
|
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
|
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
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
23
|
18
|
8
|
10
|
|
Overall Study
COMPLETED
|
23
|
18
|
8
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Leucine for Depression Study (L-DEP)
Baseline characteristics by cohort
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
35.2 years
STANDARD_DEVIATION 16.3 • n=5 Participants
|
26.8 years
STANDARD_DEVIATION 12.7 • n=7 Participants
|
33.1 years
STANDARD_DEVIATION 12.6 • n=5 Participants
|
31.9 years
STANDARD_DEVIATION 14.9 • n=4 Participants
|
31.8 years
STANDARD_DEVIATION 14.6 • n=21 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
35 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
51 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
23 participants
n=5 Participants
|
18 participants
n=7 Participants
|
8 participants
n=5 Participants
|
10 participants
n=4 Participants
|
59 participants
n=21 Participants
|
|
Body-mass index
|
24.3 kg/m^2
STANDARD_DEVIATION 4.0 • n=5 Participants
|
23.6 kg/m^2
STANDARD_DEVIATION 3.0 • n=7 Participants
|
26.3 kg/m^2
STANDARD_DEVIATION 2.9 • n=5 Participants
|
25.5 kg/m^2
STANDARD_DEVIATION 4.0 • n=4 Participants
|
24.6 kg/m^2
STANDARD_DEVIATION 3.6 • n=21 Participants
|
PRIMARY outcome
Timeframe: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administrationDepression 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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Change in Depressed Mood From Baseline
3 hours
|
.5909091 score on a scale
Standard Deviation 2.363595
|
.5625 score on a scale
Standard Deviation 1.364734
|
.375 score on a scale
Standard Deviation 1.06066
|
.1111111 score on a scale
Standard Deviation .3333333
|
|
Change in Depressed Mood From Baseline
4 hours
|
.4285714 score on a scale
Standard Deviation 1.963961
|
.3333333 score on a scale
Standard Deviation .9701425
|
.1428571 score on a scale
Standard Deviation .3779645
|
0 score on a scale
Standard Deviation 0
|
|
Change in Depressed Mood From Baseline
5 hours
|
.4545455 score on a scale
Standard Deviation 2.132007
|
.0555556 score on a scale
Standard Deviation .2357023
|
.1666667 score on a scale
Standard Deviation .4082483
|
0 score on a scale
Standard Deviation 0
|
|
Change in Depressed Mood From Baseline
6 hours
|
.5238095 score on a scale
Standard Deviation 2.182179
|
0 score on a scale
Standard Deviation 0
|
.1428571 score on a scale
Standard Deviation .3779645
|
0 score on a scale
Standard Deviation 0
|
|
Change in Depressed Mood From Baseline
Baseline
|
.6818182 score on a scale
Standard Deviation 1.86155
|
.5294118 score on a scale
Standard Deviation 1.178858
|
.2857143 score on a scale
Standard Deviation .48795
|
.6 score on a scale
Standard Deviation 1.074968
|
|
Change in Depressed Mood From Baseline
1 hour
|
1.619048 score on a scale
Standard Deviation 3.879126
|
.7647059 score on a scale
Standard Deviation 1.480262
|
.375 score on a scale
Standard Deviation .7440238
|
0 score on a scale
Standard Deviation 0
|
|
Change in Depressed Mood From Baseline
1.5 hours
|
1.55 score on a scale
Standard Deviation 3.817894
|
1 score on a scale
Standard Deviation 2.371708
|
.25 score on a scale
Standard Deviation .46291
|
.1 score on a scale
Standard Deviation .3162278
|
|
Change in Depressed Mood From Baseline
2 hours
|
1 score on a scale
Standard Deviation 3.829708
|
1.111111 score on a scale
Standard Deviation 3.103866
|
.7142857 score on a scale
Standard Deviation 1.253566
|
.4 score on a scale
Standard Deviation .6992059
|
SECONDARY outcome
Timeframe: At baseline and then at 2 and 4 hours after LPS (or saline) administrationMontgomery-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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Change in Depressive Symptoms From Baseline
Baseline
|
2.086957 score on a scale
Standard Deviation 2.574579
|
2.125 score on a scale
Standard Deviation 3.052322
|
2.5 score on a scale
Standard Deviation 3.891382
|
1.222222 score on a scale
Standard Deviation 1.301708
|
|
Change in Depressive Symptoms From Baseline
2 hours
|
3 score on a scale
Standard Deviation 5.485913
|
4 score on a scale
Standard Deviation 6.184658
|
1.875 score on a scale
Standard Deviation 2.295181
|
.7 score on a scale
Standard Deviation .9486833
|
|
Change in Depressive Symptoms From Baseline
4 hours
|
1.045455 score on a scale
Standard Deviation 1.812057
|
1.529412 score on a scale
Standard Deviation 1.907801
|
2.142857 score on a scale
Standard Deviation 1.864454
|
.2 score on a scale
Standard Deviation .421637
|
SECONDARY outcome
Timeframe: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administrationFeelings 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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Change in Feelings of Social Disconnection From Baseline
4 hours
|
15.71429 score on a scale
Standard Deviation 7.26046
|
16.66667 score on a scale
Standard Deviation 9.749811
|
16.42857 score on a scale
Standard Deviation 6.803361
|
19.6 score on a scale
Standard Deviation 19.65932
|
|
Change in Feelings of Social Disconnection From Baseline
5 hours
|
16.28571 score on a scale
Standard Deviation 7.444077
|
19.38889 score on a scale
Standard Deviation 13.3775
|
19.5 score on a scale
Standard Deviation 10.96814
|
17.6 score on a scale
Standard Deviation 14.19859
|
|
Change in Feelings of Social Disconnection From Baseline
Baseline
|
22.52381 score on a scale
Standard Deviation 7.639496
|
24 score on a scale
Standard Deviation 8.581786
|
22.57143 score on a scale
Standard Deviation 6.704654
|
21.6 score on a scale
Standard Deviation 10.7827
|
|
Change in Feelings of Social Disconnection From Baseline
1 hour
|
16.65217 score on a scale
Standard Deviation 7.327462
|
17.83333 score on a scale
Standard Deviation 9.463552
|
18 score on a scale
Standard Deviation 6.21059
|
15.44444 score on a scale
Standard Deviation 12.26898
|
|
Change in Feelings of Social Disconnection From Baseline
1.5 hours
|
16.86364 score on a scale
Standard Deviation 7.942025
|
16.77778 score on a scale
Standard Deviation 9.42809
|
17.125 score on a scale
Standard Deviation 6.220645
|
13.625 score on a scale
Standard Deviation 7.836499
|
|
Change in Feelings of Social Disconnection From Baseline
2 hours
|
15.33333 score on a scale
Standard Deviation 7.308335
|
17.05556 score on a scale
Standard Deviation 9.276613
|
17 score on a scale
Standard Deviation 6.546537
|
18.3 score on a scale
Standard Deviation 14.95215
|
|
Change in Feelings of Social Disconnection From Baseline
3 hours
|
15.38095 score on a scale
Standard Deviation 6.6744
|
15.8125 score on a scale
Standard Deviation 9.914426
|
18 score on a scale
Standard Deviation 5.744563
|
13.55556 score on a scale
Standard Deviation 9.166667
|
|
Change in Feelings of Social Disconnection From Baseline
6 hours
|
16.25 score on a scale
Standard Deviation 7.27559
|
17.72222 score on a scale
Standard Deviation 8.68945
|
14.57143 score on a scale
Standard Deviation 7.807201
|
19.9 score on a scale
Standard Deviation 18.62167
|
SECONDARY outcome
Timeframe: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administrationFatigue 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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Change in Fatigue From Baseline
Baseline
|
2.409091 score on a scale
Standard Deviation 2.839502
|
2.117647 score on a scale
Standard Deviation 2.027386
|
1.857143 score on a scale
Standard Deviation 3.338092
|
2 score on a scale
Standard Deviation 1.885618
|
|
Change in Fatigue From Baseline
1 hours
|
3.666667 score on a scale
Standard Deviation 4.09064
|
3.611111 score on a scale
Standard Deviation 3.310214
|
2.25 score on a scale
Standard Deviation 3.412163
|
.6666667 score on a scale
Standard Deviation .8660254
|
|
Change in Fatigue From Baseline
1.5 hours
|
5.095238 score on a scale
Standard Deviation 5.290603
|
4.444444 score on a scale
Standard Deviation 2.994548
|
2.25 score on a scale
Standard Deviation 4.399675
|
1 score on a scale
Standard Deviation 1.247219
|
|
Change in Fatigue From Baseline
2 hours
|
4.681818 score on a scale
Standard Deviation 5.083928
|
4.333333 score on a scale
Standard Deviation 3.694193
|
2.375 score on a scale
Standard Deviation 3.73927
|
.9 score on a scale
Standard Deviation 1.449138
|
|
Change in Fatigue From Baseline
3 hours
|
4.590909 score on a scale
Standard Deviation 4.584229
|
3.555556 score on a scale
Standard Deviation 3.014128
|
2.625 score on a scale
Standard Deviation 4.10357
|
1.777778 score on a scale
Standard Deviation 1.855921
|
|
Change in Fatigue From Baseline
4 hours
|
3.272727 score on a scale
Standard Deviation 4.322497
|
2.111111 score on a scale
Standard Deviation 2.246275
|
2.571429 score on a scale
Standard Deviation 4.197505
|
.6 score on a scale
Standard Deviation 1.074968
|
|
Change in Fatigue From Baseline
5 hours
|
3.454545 score on a scale
Standard Deviation 4.925418
|
2.222222 score on a scale
Standard Deviation 2.438793
|
2.833333 score on a scale
Standard Deviation 4.167333
|
1.3 score on a scale
Standard Deviation 1.946507
|
|
Change in Fatigue From Baseline
6 hours
|
2.666667 score on a scale
Standard Deviation 4.564355
|
1.944444 score on a scale
Standard Deviation 2.508157
|
1.571429 score on a scale
Standard Deviation 2.935821
|
1 score on a scale
Standard Deviation 1.581139
|
SECONDARY outcome
Timeframe: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administrationConfusion 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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Change in Confusion From Baseline
Baseline
|
1.409091 score on a scale
Standard Deviation 1.991867
|
1.125 score on a scale
Standard Deviation 1.408309
|
1 score on a scale
Standard Deviation 1.825742
|
1.1 score on a scale
Standard Deviation 1.286684
|
|
Change in Confusion From Baseline
1 hours
|
2.238095 score on a scale
Standard Deviation 3.845839
|
.8888889 score on a scale
Standard Deviation 1.07861
|
1 score on a scale
Standard Deviation 1.414214
|
.4444444 score on a scale
Standard Deviation 1.013794
|
|
Change in Confusion From Baseline
3 hours
|
1.454545 score on a scale
Standard Deviation 2.063914
|
.8888889 score on a scale
Standard Deviation 1.131833
|
.625 score on a scale
Standard Deviation 1.06066
|
.3333333 score on a scale
Standard Deviation .7071068
|
|
Change in Confusion From Baseline
4 hours
|
.6363636 score on a scale
Standard Deviation 1.216766
|
.6111111 score on a scale
Standard Deviation 1.195033
|
.5714286 score on a scale
Standard Deviation 1.133893
|
0 score on a scale
Standard Deviation 0
|
|
Change in Confusion From Baseline
1.5 hours
|
2.095238 score on a scale
Standard Deviation 3.462727
|
1.222222 score on a scale
Standard Deviation 1.308594
|
.375 score on a scale
Standard Deviation 1.06066
|
.1 score on a scale
Standard Deviation .3162278
|
|
Change in Confusion From Baseline
2 hours
|
1.772727 score on a scale
Standard Deviation 3.435554
|
1.111111 score on a scale
Standard Deviation 1.323493
|
.625 score on a scale
Standard Deviation 1.407886
|
.1 score on a scale
Standard Deviation .3162278
|
|
Change in Confusion From Baseline
5 hours
|
.6363636 score on a scale
Standard Deviation 1.398824
|
.6111111 score on a scale
Standard Deviation 1.036901
|
.5 score on a scale
Standard Deviation .5773503
|
.1 score on a scale
Standard Deviation .3162278
|
|
Change in Confusion From Baseline
6 hours
|
.4761905 score on a scale
Standard Deviation 1.435933
|
.4705882 score on a scale
Standard Deviation 1.06757
|
.1428571 score on a scale
Standard Deviation .3779645
|
0 score on a scale
Standard Deviation 0
|
SECONDARY outcome
Timeframe: At baseline and then 3 hours after LPS (or saline) administrationMemory 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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Change in Memory Domains of Cognitive Function From Baseline
Verbal memory baseline
|
51.30435 score on a scale
Standard Deviation 8.298054
|
53.23529 score on a scale
Standard Deviation 6.139314
|
51.125 score on a scale
Standard Deviation 4.580627
|
52.3 score on a scale
Standard Deviation 8.525126
|
|
Change in Memory Domains of Cognitive Function From Baseline
Verbal memory 3 hours
|
48.66667 score on a scale
Standard Deviation 5.695027
|
52.58824 score on a scale
Standard Deviation 6.538911
|
48.5 score on a scale
Standard Deviation 5.976143
|
45.5 score on a scale
Standard Deviation 10.31988
|
|
Change in Memory Domains of Cognitive Function From Baseline
Visual memory baseline
|
44.04348 score on a scale
Standard Deviation 6.588408
|
47.76471 score on a scale
Standard Deviation 5.695716
|
46.125 score on a scale
Standard Deviation 6.490377
|
43.9 score on a scale
Standard Deviation 8.736259
|
|
Change in Memory Domains of Cognitive Function From Baseline
Visual memory 3 hours
|
42.2381 score on a scale
Standard Deviation 6.106593
|
46.29412 score on a scale
Standard Deviation 7.405781
|
41.75 score on a scale
Standard Deviation 4.26782
|
40.9 score on a scale
Standard Deviation 9.097619
|
SECONDARY outcome
Timeframe: At baseline and then 3 hours after LPS (or saline) administrationNon-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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=23 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Change in Non-memory Domains of Cognitive Function From Baseline
Shifting attention baseline
|
1014.174 milliseconds
Standard Deviation 199.4204
|
899.6471 milliseconds
Standard Deviation 140.7502
|
935.75 milliseconds
Standard Deviation 185.7423
|
947.9 milliseconds
Standard Deviation 140.4457
|
|
Change in Non-memory Domains of Cognitive Function From Baseline
Shifting attention 3 hours
|
957.2857 milliseconds
Standard Deviation 211.8759
|
829.7647 milliseconds
Standard Deviation 131.7823
|
943 milliseconds
Standard Deviation 109.6696
|
957.5 milliseconds
Standard Deviation 156.2358
|
|
Change in Non-memory Domains of Cognitive Function From Baseline
Continuous performance baseline
|
449.1304 milliseconds
Standard Deviation 73.88954
|
426 milliseconds
Standard Deviation 44.63743
|
442.25 milliseconds
Standard Deviation 27.41089
|
458.2 milliseconds
Standard Deviation 44.96122
|
|
Change in Non-memory Domains of Cognitive Function From Baseline
Stroop test 3 hours
|
386.2381 milliseconds
Standard Deviation 93.90842
|
316.2353 milliseconds
Standard Deviation 53.88475
|
324.25 milliseconds
Standard Deviation 36.86946
|
337.4 milliseconds
Standard Deviation 45.80442
|
|
Change in Non-memory Domains of Cognitive Function From Baseline
Stroop test baseline
|
356.913 milliseconds
Standard Deviation 95.80563
|
307.6471 milliseconds
Standard Deviation 57.51515
|
304.125 milliseconds
Standard Deviation 38.96679
|
268.8 milliseconds
Standard Deviation 146.5619
|
|
Change in Non-memory Domains of Cognitive Function From Baseline
Continuous performance 3 hours
|
456.619 milliseconds
Standard Deviation 65.31422
|
423.8235 milliseconds
Standard Deviation 54.88993
|
439.25 milliseconds
Standard Deviation 35.05812
|
460.6 milliseconds
Standard Deviation 55.05795
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 hours after LPS (or saline) administrationPopulation: 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.
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
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 hours after LPS (or saline) administrationUsing 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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=20 Participants
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
|
PO Placebo & IV LPS
n=17 Participants
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
|
PO Leucine & IV Placebo
n=8 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Subjective Sensitivity to Social Rejection
|
18.05 score on a scale
Standard Deviation 5.670561
|
16.17647 score on a scale
Standard Deviation 5.282463
|
18.25 score on a scale
Standard Deviation 7.245688
|
17.6 score on a scale
Standard Deviation 5.481281
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 hours after LPS (or saline) administrationPopulation: 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.
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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 hours after drug administrationPrior 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.
Outcome measures
| Measure |
PO Leucine & IV LPS
n=21 Participants
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
|
PO Placebo & IV LPS
n=18 Participants
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
|
PO Leucine & IV Placebo
n=7 Participants
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
|
PO Placebo & IV Placebo
n=10 Participants
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
|
|---|---|---|---|---|
|
Subjective Sensitivity to Social Acceptance
|
76.7619 score on a scale
Standard Deviation 9.229869
|
77.38889 score on a scale
Standard Deviation 5.94226
|
76.28571 score on a scale
Standard Deviation 3.77334
|
78.3 score on a scale
Standard Deviation 6.037844
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 hours after LPS (or saline) administrationPopulation: 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.
Reward Learning Task (a laboratory based probabilistic reward task that objectively measures participants' ability to modulate behavior as a function of reward)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administrationPopulation: 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.
Plasma proinflammatory cytokines (interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, and soluble tumor necrosis factor receptor)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administrationPopulation: 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.
Plasma tryptophan, kynurenine, quinolinic acid, and kynurenic acid
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: At baseline and 30 minutes after LPS (or saline) administrationPopulation: 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.
Genome-wide transcriptional profiling conducted using Illumina HT-12 BeadArrays
Outcome measures
Outcome data not reported
Adverse Events
PO Leucine & IV LPS
PO Placebo & IV LPS
PO Leucine & IV Placebo
PO Placebo & IV 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