Trial Outcomes & Findings for A Trial of the Fatty Acid Amide Hydrolase Inhibitor Palmitoylethanolamide in Bipolar Depression (NCT NCT06229977)
NCT ID: NCT06229977
Last Updated: 2026-08-13
Results Overview
The Hamilton Depression Rating Scale measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity. The change in score will be reported. The change in score will be reported as the \[(Score at 6 weeks follow up) - (Score at Baseline)\] - A negative value indicates improvement of depression severity.
COMPLETED
PHASE2
34 participants
Baseline, 6 weeks follow up
2026-08-13
Participant Flow
Participant milestones
| Measure |
PEA Plus Treatment as Usual (TAU)
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
16
|
|
Overall Study
COMPLETED
|
16
|
12
|
|
Overall Study
NOT COMPLETED
|
2
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Trial of the Fatty Acid Amide Hydrolase Inhibitor Palmitoylethanolamide in Bipolar Depression
Baseline characteristics by cohort
| Measure |
PEA Plus Treatment as Usual (TAU)
n=18 Participants
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
n=16 Participants
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=1 Participants
|
16 Participants
n=1 Participants
|
32 Participants
n=1 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
2 Participants
n=1 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=1 Participants
|
13 Participants
n=1 Participants
|
25 Participants
n=1 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=1 Participants
|
3 Participants
n=1 Participants
|
9 Participants
n=1 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=1 Participants
|
1 Participants
n=1 Participants
|
1 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=1 Participants
|
4 Participants
n=1 Participants
|
8 Participants
n=1 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=1 Participants
|
11 Participants
n=1 Participants
|
25 Participants
n=1 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
0 Participants
n=1 Participants
|
|
Region of Enrollment
United States
|
18 Participants
n=1 Participants
|
16 Participants
n=1 Participants
|
34 Participants
n=1 Participants
|
|
Montgomery Äsberg Depression Rating Scale Score
|
29 score on a scale
STANDARD_DEVIATION 2 • n=1 Participants
|
28 score on a scale
STANDARD_DEVIATION 2 • n=1 Participants
|
28 score on a scale
STANDARD_DEVIATION 1 • n=1 Participants
|
|
Hamilton Depression Rating Scale Score
|
21 score on a scale
STANDARD_DEVIATION 1 • n=1 Participants
|
21 score on a scale
STANDARD_DEVIATION 1 • n=1 Participants
|
21 score on a scale
STANDARD_DEVIATION 1 • n=1 Participants
|
|
Columbia Suicide Severity Rating Scale (C-SSRS) Risk Score
|
1 score on a scale
STANDARD_DEVIATION 0 • n=1 Participants
|
1 score on a scale
STANDARD_DEVIATION 0 • n=1 Participants
|
1 score on a scale
STANDARD_DEVIATION 0 • n=1 Participants
|
PRIMARY outcome
Timeframe: Baseline, 6 weeks follow upPopulation: Analysis includes participants with both a baseline and a Visit 4 (Week 6) Hamilton Depression Rating Scale (HAM-D) score available. 2 participants from the PEA plus Treatment as Usual (TAU) arm and 4 participants from the Placebo plus Treatment as Usual (TAU) arm discontinued the study prior to Visit 4 or had a missing Visit 4 assessment and were excluded.
The Hamilton Depression Rating Scale measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity. The change in score will be reported. The change in score will be reported as the \[(Score at 6 weeks follow up) - (Score at Baseline)\] - A negative value indicates improvement of depression severity.
Outcome measures
| Measure |
PEA Plus Treatment as Usual (TAU)
n=16 Participants
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
n=12 Participants
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
|---|---|---|
|
Change in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D)
|
-12.38 score on a scale
Interval -15.93 to -8.83
|
-13.03 score on a scale
Interval -16.78 to -9.28
|
SECONDARY outcome
Timeframe: from baseline to end of study (6 week follow up)Population: Analysis includes participants with both a baseline and a Visit 4 (Week 6) Hamilton Depression Rating Scale (HAM-D) score available. 2 participants from the PEA plus Treatment as Usual (TAU) arm and 4 participants from the Placebo plus Treatment as Usual (TAU) arm discontinued the study prior to Visit 4 or had a missing Visit 4 assessment and were excluded.
Remission of depressive symptoms is defined by a HAM-D score of ≤7. The Hamilton Depression Rating Scale (HAM-D) measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity
Outcome measures
| Measure |
PEA Plus Treatment as Usual (TAU)
n=16 Participants
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
n=12 Participants
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
|---|---|---|
|
Number of Participants That Show a Remission of Depressive Symptoms as Assessed by the HAM-D Scale
|
7 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: from baseline to end of study (6 week follow up)Population: Analysis includes participants with both a baseline and a Visit 4 (Week 6) Hamilton Depression Rating Scale (HAM-D) score available. 2 participants from the PEA plus Treatment as Usual (TAU) arm and 4 participants from the Placebo plus Treatment as Usual (TAU) arm discontinued the study prior to Visit 4 or had a missing Visit 4 assessment and were excluded.
Response rate is defined by ≥ 50 % reduction in HAM-D Score from baseline. The Hamilton Depression Rating Scale (HAM-D) measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity
Outcome measures
| Measure |
PEA Plus Treatment as Usual (TAU)
n=16 Participants
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
n=12 Participants
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
|---|---|---|
|
Number of Participants That Show a Response as Assessed by the HAM-D Scale
|
9 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks follow upPopulation: Analysis includes participants with both a baseline and a Visit 4 (Week 6) Montgomery-Åsberg Depression Rating Scale (MADRS) score available. 3 participants from the PEA plus Treatment as Usual (TAU) arm and 4 participants from the Placebo plus Treatment as Usual (TAU) arm discontinued the study prior to Visit 4 or had a missing Visit 4 assessment and were excluded.
The Montgomery Äsberg Depression Rating Scale measures severity in depression. The total score ranges from 0 to 60, a higher score indicating greater depression. The change in score will be reported. The change in score will be reported as the \[(Score at 6 weeks follow up) - (Score at Baseline)\] - A negative value indicates improvement of depression severity.
Outcome measures
| Measure |
PEA Plus Treatment as Usual (TAU)
n=15 Participants
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
n=12 Participants
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
|---|---|---|
|
Change in Depression as Assessed by the Montgomery Äsberg Depression Rating Scale (MADRS)
|
-15.97 score on a scale
Interval -22.48 to -9.46
|
-18.22 score on a scale
Interval -25.14 to -11.3
|
SECONDARY outcome
Timeframe: Baseline To Week 6Population: Analysis includes all randomized participants in each arm who had at least one post-baseline HAM-D assessment available.
Time to first study visit at which a participant achieved ≥50% reduction from baseline HAM-D total score. The Hamilton Depression Rating Scale (HAM-D) measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity
Outcome measures
| Measure |
PEA Plus Treatment as Usual (TAU)
n=17 Participants
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
n=14 Participants
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
|---|---|---|
|
Time to Response - HAM-D (≥50% Reduction From Baseline)
|
4 Weeks
Interval 2.0 to 6.0
|
2 Weeks
Interval 2.0 to 4.0
|
Adverse Events
PEA Plus Treatment as Usual (TAU)
Placebo Plus Treatment as Usual (TAU)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PEA Plus Treatment as Usual (TAU)
n=18 participants at risk
Palmitoylethanolamide administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
Placebo Plus Treatment as Usual (TAU)
n=16 participants at risk
Matching placebo administered orally in addition to participants' existing mood stabilizer/antipsychotic/antidepressant regimen
|
|---|---|---|
|
Nervous system disorders
Headache
|
5.6%
1/18 • Number of events 2 • 6 weeks
|
6.2%
1/16 • Number of events 2 • 6 weeks
|
|
Nervous system disorders
Vertigo
|
5.6%
1/18 • Number of events 1 • 6 weeks
|
0.00%
0/16 • 6 weeks
|
|
Immune system disorders
Dry Mouth
|
5.6%
1/18 • Number of events 1 • 6 weeks
|
6.2%
1/16 • Number of events 1 • 6 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia (Aching Joints)
|
5.6%
1/18 • Number of events 1 • 6 weeks
|
0.00%
0/16 • 6 weeks
|
|
Endocrine disorders
Decreased Appetite
|
5.6%
1/18 • Number of events 1 • 6 weeks
|
0.00%
0/16 • 6 weeks
|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
0.00%
0/18 • 6 weeks
|
6.2%
1/16 • Number of events 1 • 6 weeks
|
Additional Information
Dr. Rodrigo Machado-Vieira
The University of Texas Health Science Center at Houston
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place