Trial Outcomes & Findings for The Effects of Kynurenine Aminotransferase Inhibition in People With Schizophrenia (NCT NCT04013555)
NCT ID: NCT04013555
Last Updated: 2026-02-11
Results Overview
The investigators will use the kynurenine serum measures to examine whether NAC compared to placebo blocks the peripheral conversion of kynurenine to KYNA.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
88 participants
Primary outcome timeframe
Baseline, 1 hour and 4 hours on each Challenge Day
Results posted on
2026-02-11
Participant Flow
Eighty-eight people were screened and consented for study participation. Fourteen participants were excluded and 4 were withdrawn prior to randomization. Seventy people were randomized.
Participant milestones
| Measure |
N-acetylcysteine, Then Placebo
On Challenge Day 1, participants first received N-acetylcysteine, 140 mg/kg up to a maximum of 15 g. Thirty minutes after N-acetylcysteine administration participants received Tryptophan, 6 grams.
On Challenge Day 2 (at least two weeks after Challenge Day #1), participants first received placebo, 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants received Tryptophan, 6 grams.
N-acetylcysteine (NAC): Flavored effervescent formulation
Placebo: Flavored effervescent formulation designed to mimic N-acetylcysteine.
Tryptophan: Oral slurry form
|
Placebo, Then N-acetylcysteine
On Challenge Day #1, participants first received placebo, 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants received Tryptophan, 6 grams.
On Challenge Day #2 (at least 2 weeks after Challenge Day #1), participants first received N-acetylcysteine, 140 mg.kg up to a maximum of 15g. Thirty minutes after placebo administration participants received Tryptophan, 6 grams.
N-acetylcysteine (NAC): Flavored effervescent formulation
Placebo: Flavored effervescent formulation designed to mimic N-acetylcysteine.
Tryptophan: Oral slurry form
|
|---|---|---|
|
Challenge Day #1
STARTED
|
36
|
34
|
|
Challenge Day #1
COMPLETED
|
29
|
29
|
|
Challenge Day #1
NOT COMPLETED
|
7
|
5
|
|
Challenge Day #2
STARTED
|
28
|
29
|
|
Challenge Day #2
COMPLETED
|
25
|
26
|
|
Challenge Day #2
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Effects of Kynurenine Aminotransferase Inhibition in People With Schizophrenia
Baseline characteristics by cohort
| Measure |
N-acetylcysteine, Then Placebo
n=36 Participants
On Challenge Day 1, participants first received N-acetylcysteine, 140 mg/kg up to a maximum of 15 g. Thirty minutes after N-acetylcysteine administration participants received Tryptophan, 6 grams.
On Challenge Day 2 (at least two weeks after Challenge Day #1), participants first received placebo, 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants received Tryptophan, 6 grams.
|
Placebo, Then N-acetylcysteine
n=34 Participants
On Challenge Day #1, participants first received placebo, 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants received Tryptophan, 6 grams.
On Challenge Day #2 (at least 2 weeks after Challenge Day #1), participants first received N-acetylcysteine, 140 mg.kg up to a maximum of 15g. Thirty minutes after placebo administration participants received Tryptophan, 6 grams.
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
36 Participants
n=41 Participants
|
34 Participants
n=1581 Participants
|
70 Participants
n=4626 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=41 Participants
|
10 Participants
n=1581 Participants
|
20 Participants
n=4626 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=41 Participants
|
24 Participants
n=1581 Participants
|
50 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
1 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Black or African American
|
18 Participants
n=41 Participants
|
15 Participants
n=1581 Participants
|
33 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=41 Participants
|
16 Participants
n=1581 Participants
|
32 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=41 Participants
|
2 Participants
n=1581 Participants
|
3 Participants
n=4626 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
1 Participants
n=1581 Participants
|
1 Participants
n=4626 Participants
|
|
Region of Enrollment
United States
|
36 participants
n=41 Participants
|
34 participants
n=1581 Participants
|
70 participants
n=4626 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 hour and 4 hours on each Challenge DayPopulation: Participants who completed at least one Challenge Day
The investigators will use the kynurenine serum measures to examine whether NAC compared to placebo blocks the peripheral conversion of kynurenine to KYNA.
Outcome measures
| Measure |
N-acetylcysteine & Tryptophan
n=54 Participants
N-acetylcysteine 140 mg/kg up to a maximum of 15 g. Thirty minutes after N-acetylcysteine administration participants will receive Tryptophan, 6 grams.
N-acetylcysteine (NAC): Flavored effervescent formulation
Tryptophan: Oral slurry form
|
Placebo & Tryptophan
n=54 Participants
Placebo 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants will receive Tryptophan, 6 grams.
Placebo: Flavored effervescent formulation designed to mimic NAC
Tryptophan: Oral slurry form
|
|---|---|---|
|
Serum Kynurenine Levels
Baseline
|
2.39 pmoles/ul
Standard Deviation 1.89
|
1.97 pmoles/ul
Standard Deviation 1.22
|
|
Serum Kynurenine Levels
1 hour
|
22.0 pmoles/ul
Standard Deviation 18.4
|
23.3 pmoles/ul
Standard Deviation 37.3
|
|
Serum Kynurenine Levels
4 hours
|
65.8 pmoles/ul
Standard Deviation 51.6
|
94.0 pmoles/ul
Standard Deviation 159.5
|
PRIMARY outcome
Timeframe: Baseline, 1 hour and 4 hours on each Challenge DayPopulation: Participants who completed at least one Challenge Day
The investigators will use the KYNA serum measures to examine whether NAC compared to placebo blocks the peripheral conversion of kynurenine to KYNA.
Outcome measures
| Measure |
N-acetylcysteine & Tryptophan
n=54 Participants
N-acetylcysteine 140 mg/kg up to a maximum of 15 g. Thirty minutes after N-acetylcysteine administration participants will receive Tryptophan, 6 grams.
N-acetylcysteine (NAC): Flavored effervescent formulation
Tryptophan: Oral slurry form
|
Placebo & Tryptophan
n=54 Participants
Placebo 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants will receive Tryptophan, 6 grams.
Placebo: Flavored effervescent formulation designed to mimic NAC
Tryptophan: Oral slurry form
|
|---|---|---|
|
Kynurenic Acid Levels
Baseline
|
48.1 fmoles/ul
Standard Deviation 50.9
|
42.9 fmoles/ul
Standard Deviation 35.2
|
|
Kynurenic Acid Levels
1 hour
|
1687 fmoles/ul
Standard Deviation 3463
|
1322 fmoles/ul
Standard Deviation 3382
|
|
Kynurenic Acid Levels
4 hours
|
5758 fmoles/ul
Standard Deviation 4850
|
7471 fmoles/ul
Standard Deviation 6930
|
PRIMARY outcome
Timeframe: Baseline, 2 hours on each Challenge DayPopulation: Participants who completed at least one Challenge Day
The investigators will use a Pseudo-continuous Arterial Spin Labeling (pCASL) sequence, which provides full brain coverage with high spatial resolution and excellent WM signal-to-noise ratio (SNR) (SNR\>15), to measure whole brain gray matter cerebral blood flow (CBF). The investigators will use the pCASL CBF measures to examine whether NAC compared to placebo attenuates the effects of TRYP on ASL CBF measures.
Outcome measures
| Measure |
N-acetylcysteine & Tryptophan
n=53 Participants
N-acetylcysteine 140 mg/kg up to a maximum of 15 g. Thirty minutes after N-acetylcysteine administration participants will receive Tryptophan, 6 grams.
N-acetylcysteine (NAC): Flavored effervescent formulation
Tryptophan: Oral slurry form
|
Placebo & Tryptophan
n=54 Participants
Placebo 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants will receive Tryptophan, 6 grams.
Placebo: Flavored effervescent formulation designed to mimic NAC
Tryptophan: Oral slurry form
|
|---|---|---|
|
Whole Brain Gray Matter Cerebral Blood Flow (CBF)
Baseline
|
49.9 ml/100 g/min
Standard Deviation 11.0
|
52.5 ml/100 g/min
Standard Deviation 10.3
|
|
Whole Brain Gray Matter Cerebral Blood Flow (CBF)
2 hours
|
54.4 ml/100 g/min
Standard Deviation 12.0
|
57.3 ml/100 g/min
Standard Deviation 12.2
|
Adverse Events
N-acetylcysteine & Tryptophan
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo & Tryptophan
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
N-acetylcysteine & Tryptophan
n=63 participants at risk
N-acetylcysteine 140 mg/kg up to a maximum of 15 g. Thirty minutes after N-acetylcysteine administration participants will receive Tryptophan, 6 grams.
N-acetylcysteine (NAC): Flavored effervescent formulation
Tryptophan: Oral slurry form
|
Placebo & Tryptophan
n=64 participants at risk
Placebo 140 mg/kg up to a maximum of 15 g. Thirty minutes after placebo administration participants will receive Tryptophan, 6 grams.
Placebo: Flavored effervescent formulation designed to mimic NAC
Tryptophan: Oral slurry form
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
3.2%
2/63 • Over 4 study visits (over 6-8 weeks)
|
6.9%
2/29 • Over 4 study visits (over 6-8 weeks)
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
2/63 • Over 4 study visits (over 6-8 weeks)
|
6.9%
2/29 • Over 4 study visits (over 6-8 weeks)
|
|
Ear and labyrinth disorders
Dizziness
|
1.6%
1/63 • Over 4 study visits (over 6-8 weeks)
|
6.9%
2/29 • Over 4 study visits (over 6-8 weeks)
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/63 • Over 4 study visits (over 6-8 weeks)
|
3.4%
1/29 • Over 4 study visits (over 6-8 weeks)
|
Additional Information
Dr. Robert Buchanan
Maryland Psychiatric Research Center
Phone: 410-402-7876
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place