Trial Outcomes & Findings for Study of Naltrexone-Induced Blockade of Antidepressant Effects (NCT NCT04322526)
NCT ID: NCT04322526
Last Updated: 2020-04-21
Results Overview
In order to identify the neural correlates of contextual processing, we examined changes in blood oxygenation level-dependent (BOLD) signal during the post-placebo fMRI scanning session.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
25 participants
Primary outcome timeframe
[Approximately at day 1, 7]
Results posted on
2020-04-21
Participant Flow
Participant milestones
| Measure |
Naltrexone, Then Placebo
In the naltrexone and then placebo arm, participants receive one-dose naltrexone 50mg one hour before a first fMRI scanning session on visit 1 followed by a one-dose placebo pill one hour before a second fMRI scanning session on visit 2.
Naltrexone 50 Mg Oral Tablet: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).
Placebo oral tablet: Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
|
Placebo, Then Naltrexone
In the placebo and then naltrexone arm, participants receive one-dose of placebo pill one hour before a first fMRI scanning session on visit 1 followed by a one-dose naltrexone 50mg one hour before a second fMRI scanning session on visit 2.
Naltrexone 50 Mg Oral Tablet: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).
Placebo oral tablet: Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
|
|---|---|---|
|
First Intervention (1 Day)
STARTED
|
13
|
12
|
|
First Intervention (1 Day)
COMPLETED
|
12
|
11
|
|
First Intervention (1 Day)
NOT COMPLETED
|
1
|
1
|
|
Washout (1 Week)
STARTED
|
12
|
11
|
|
Washout (1 Week)
COMPLETED
|
11
|
9
|
|
Washout (1 Week)
NOT COMPLETED
|
1
|
2
|
|
Second Intervention (1day)
STARTED
|
11
|
9
|
|
Second Intervention (1day)
COMPLETED
|
11
|
9
|
|
Second Intervention (1day)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Naltrexone, Then Placebo
In the naltrexone and then placebo arm, participants receive one-dose naltrexone 50mg one hour before a first fMRI scanning session on visit 1 followed by a one-dose placebo pill one hour before a second fMRI scanning session on visit 2.
Naltrexone 50 Mg Oral Tablet: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).
Placebo oral tablet: Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
|
Placebo, Then Naltrexone
In the placebo and then naltrexone arm, participants receive one-dose of placebo pill one hour before a first fMRI scanning session on visit 1 followed by a one-dose naltrexone 50mg one hour before a second fMRI scanning session on visit 2.
Naltrexone 50 Mg Oral Tablet: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).
Placebo oral tablet: Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
|
|---|---|---|
|
First Intervention (1 Day)
Withdrawal by Subject
|
1
|
1
|
|
Washout (1 Week)
Lost to Follow-up
|
1
|
2
|
Baseline Characteristics
Study of Naltrexone-Induced Blockade of Antidepressant Effects
Baseline characteristics by cohort
| Measure |
Naltrexone, Then Placebo
n=10 Participants
In the naltrexone and then placebo arm, participants receive one-dose naltrexone 50mg one hour before a first fMRI scanning session on visit 1 followed by a one-dose placebo pill one hour before a second fMRI scanning session on visit 2.
Naltrexone 50 Mg Oral Tablet: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).
Placebo oral tablet: Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
|
Placebo, Then Naltrexone
n=10 Participants
In the placebo and then naltrexone arm, participants receive one-dose of placebo pill one hour before a first fMRI scanning session on visit 1 followed by a one-dose naltrexone 50mg one hour before a second fMRI scanning session on visit 2.
Naltrexone 50 Mg Oral Tablet: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).
Placebo oral tablet: Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
25.3 years
STANDARD_DEVIATION 5.2 • n=5 Participants
|
25.9 years
STANDARD_DEVIATION 8.2 • n=7 Participants
|
25.6 years
STANDARD_DEVIATION 6.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: [Approximately at day 1, 7]Population: The goal of aim one was to identify the neural correlates of antidepressant placebo effects. This aim was accomplished by examining the neural responses to the Antidepressant placebo fMRI task during the placebo session only, regardless of whether participants were assigned to the placebo-naltrexone or the naltrexone-placebo intervention.
In order to identify the neural correlates of contextual processing, we examined changes in blood oxygenation level-dependent (BOLD) signal during the post-placebo fMRI scanning session.
Outcome measures
| Measure |
fMRI BOLD Responses in the rACC Cortex (Placebo Session)
n=20 Participants
We examined baseline brain measures of contextual processing during the placebo session only. In particular, we obtained whole-brain BOLD fMRI responses during the processing of contextual cues and extracted BOLD signal measures in the rACC.
Post-naltrexone brain responses were not used for this analysis.
|
|---|---|
|
BOLD Responses in the rACC Cortex During the Processing of Contextual Cues at Baseline (Post-placebo)
|
0.47 BOLD signal
Standard Deviation 0.76
|
PRIMARY outcome
Timeframe: [Approximately at day 1, 7]Population: The goal of aim two was to investigate the effects of one single dose of naltrexone on the neural correlates of antidepressant placebo effects. This aim was accomplished by examining changes in the neural responses to the Antidepressant placebo fMRI task from the naltrexone to the placebo session, regardless of the order of each intervention.
In order to identify naltrexone-induced changes in the neural correlates of contextual processing, we examined changes in blood oxygenation level-dependent (BOLD) during the fMRI scanning session between Naltrexone vs. placebo pill.
Outcome measures
| Measure |
fMRI BOLD Responses in the rACC Cortex (Placebo Session)
n=17 Participants
We examined baseline brain measures of contextual processing during the placebo session only. In particular, we obtained whole-brain BOLD fMRI responses during the processing of contextual cues and extracted BOLD signal measures in the rACC.
Post-naltrexone brain responses were not used for this analysis.
|
|---|---|
|
Naltrexone-induced Changes in BOLD Responses in the rACC Cortex During the Processing of Contextual Cues (Placebo vs. Naltrexone)
|
1.23 changes in BOLD signal
Standard Deviation 1.07
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Naltrexone
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=23 participants at risk
Placebo oral tablet: Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.
|
Naltrexone
n=24 participants at risk
Naltrexone 50 Mg Oral Tablet: Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).
|
|---|---|---|
|
Gastrointestinal disorders
Nausea, gastrointestinal discomfort, vomiting.
|
13.0%
3/23 • Number of events 3 • [Approximately at day 1, 7]
|
33.3%
8/24 • Number of events 8 • [Approximately at day 1, 7]
|
|
Nervous system disorders
Fatigue
|
26.1%
6/23 • Number of events 6 • [Approximately at day 1, 7]
|
41.7%
10/24 • Number of events 10 • [Approximately at day 1, 7]
|
|
Nervous system disorders
Dizziness/drowsiness
|
17.4%
4/23 • Number of events 4 • [Approximately at day 1, 7]
|
20.8%
5/24 • Number of events 5 • [Approximately at day 1, 7]
|
|
Nervous system disorders
Shaking
|
4.3%
1/23 • Number of events 1 • [Approximately at day 1, 7]
|
0.00%
0/24 • [Approximately at day 1, 7]
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place