Opioid-Related Disorders
Conditions
Brief summary
The aim of this study is to train individuals with opioid use disorder to control their brain activity in a way that has been associated with their symptoms. Participants in the experimental group will be given direct feedback regarding their brain activity while they are undergoing functional magnetic resonance imaging (fMRI) scanning, and will try to learn to control their brain activity during these feedback sessions. A separate group of participants will be given a control form of feedback that we do not believe can have clinical benefits. Our primary hypothesis is that the neurofeedback training will reduce opioid use and clinical features of opioid use disorder more than the control feedback.
Interventions
DEVICEExperimental feedback
Participants provided with feedback of target brain activation patterns (for example, in the form of a line graph) and will be instructed to try to make the line go up or down.
DEVICEControl feedback
Participants provided with control type of feedback (for example, in the form of a line graph) and will be instructed to try to make the line go up or down.
DEVICEfMRI
fMRI will be used to assess brain activity
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants will be blinded as to whether they are receiving experimental or control neurofeedback.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. non-methadone opioid positive urine screen (as assessed during standard treatment) or indicated via Utox or self-reported past-month opioid use at screening 2. Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for opioid use disorder, as assessed via structured clinical interview (SCID) 3. ≥3 months of methadone treatment
Exclusion criteria
1. Having any current neurologic or psychiatric disorders including current moderate to severe other DSM-5 substance use disorders with the exceptions of opioids, cocaine, tobacco and cannabis, as assessed using the SCID. 2. Failure to pass a magnetic resonance imaging (MRI) screening 3. Having significant underlying medical conditions requiring medications. 4. Women who are pregnant or nursing 5. Baseline scanning with excessive motion based on frame to frame displacement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Use: Urine Tests | Baseline (week 1) to one month post follow-up (week 9) | Opioid use will be monitored by weekly urine test. This will be assessed as the percentage of negative tests. |
| Opioid Use: Timeline Followback Method (TLFB) | Baseline (week 1) to one month post follow-up (week 9) | Opioid use assessed using the timeline followback method (TLFB). TLFB asks subjects to estimate drug use during a specific time period in the past. Number of participants positive or negative for drug use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Functional Connectivity Patterns in the Brain | Baseline (week 1) through follow up (week 5) | This outcome will be assessed with functional magnetic resonance imaging (fMRI) scans. Opioid abstinence network connectivity strength will be calculated during resting state (H2a). (Data was not able to be collected at MIDT and Stroop tasks as intended.) 0 represents no engagement of the opioid abstinence network. As as a novel brain network measure, there are no defined clinical cutoffs for functional connectivity. Reported is the Z-score Fisher transformed correlation coefficient. |
| Mean Opioid Craving Score | Baseline (week 1) to one month post follow-up (*week 9*) | This outcome will be measured with the Opioid Craving Scale, a 3-item measure of craving that uses a 0-10 analog scale. Total possible score is 0-30, with higher score indicating more craving. |
| Negative Affect Mean Score | Baseline (week 1) to one month post follow-up (week 9) | This outcome will be measured by the Quick Inventory of Depressive Symptomatology. This is a 16-item measure, using a 0-3 scale for each item. Total possible score is 0-48, with higher scores indicating greater symptom severity. |
Countries
United States
Participant flow
Pre-assignment details
12 participants enrolled with one participant excluded prior to randomization
Participants by arm
| Arm | Count |
|---|---|
| Neurofeedback Three imaging (fMRI) sessions of experimental feedback.
Experimental feedback: Participants provided with feedback of target brain activation patterns (for example, in the form of a line graph) and will be instructed to try to make the line go up or down. | 8 |
| Control Feedback Three imaging (fMRI) sessions of control feedback.
Control feedback (sham): Participants provided with control type of feedback (for example, in the form of a line graph) and will be instructed to try to make the line go up or down. | 3 |
| Total | 11 |
Baseline characteristics
| Characteristic | Neurofeedback | Control Feedback | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 3 Participants | 11 Participants |
| Opioid Craving Scale | 17.4 score on a scale STANDARD_DEVIATION 7.6 | 16.8 score on a scale STANDARD_DEVIATION 7.6 | 17.2 score on a scale STANDARD_DEVIATION 7.2 |
| Quick Inventory of Depressive Symptomatology | 9.0 score on a scale STANDARD_DEVIATION 5.4 | 8.7 score on a scale STANDARD_DEVIATION 4.9 | 8.9 score on a scale STANDARD_DEVIATION 5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 3 Participants | 10 Participants |
| Region of Enrollment United States | 8 participants | 3 participants | 11 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 3 |
| other Total, other adverse events | 0 / 8 | 0 / 3 |
| serious Total, serious adverse events | 0 / 8 | 0 / 3 |
Outcome results
Primary
Opioid Use: Timeline Followback Method (TLFB)
Opioid use assessed using the timeline followback method (TLFB). TLFB asks subjects to estimate drug use during a specific time period in the past. Number of participants positive or negative for drug use.
Time frame: Baseline (week 1) to one month post follow-up (week 9)
Population: Results presented here are for participants that had completed TLFB at both baseline and follow up.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Neurofeedback | Opioid Use: Timeline Followback Method (TLFB) | Baseline | Negative | 1 Participants |
| Neurofeedback | Opioid Use: Timeline Followback Method (TLFB) | Baseline | Positive | 1 Participants |
| Neurofeedback | Opioid Use: Timeline Followback Method (TLFB) | Follow up | Positive | 2 Participants |
| Neurofeedback | Opioid Use: Timeline Followback Method (TLFB) | Follow up | Negative | 0 Participants |
| Control Feedback | Opioid Use: Timeline Followback Method (TLFB) | Follow up | Positive | 2 Participants |
| Control Feedback | Opioid Use: Timeline Followback Method (TLFB) | Baseline | Negative | 1 Participants |
| Control Feedback | Opioid Use: Timeline Followback Method (TLFB) | Baseline | Positive | 1 Participants |
| Control Feedback | Opioid Use: Timeline Followback Method (TLFB) | Follow up | Negative | 0 Participants |
Primary
Opioid Use: Urine Tests
Opioid use will be monitored by weekly urine test. This will be assessed as the percentage of negative tests.
Time frame: Baseline (week 1) to one month post follow-up (week 9)
Population: One participant in the experimental group did not have any urine tests.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neurofeedback | Opioid Use: Urine Tests | 17.9 percentage of negative tests |
| Control Feedback | Opioid Use: Urine Tests | 0 percentage of negative tests |
Secondary
Mean Change in Functional Connectivity Patterns in the Brain
This outcome will be assessed with functional magnetic resonance imaging (fMRI) scans. Opioid abstinence network connectivity strength will be calculated during resting state (H2a). (Data was not able to be collected at MIDT and Stroop tasks as intended.) 0 represents no engagement of the opioid abstinence network. As as a novel brain network measure, there are no defined clinical cutoffs for functional connectivity. Reported is the Z-score Fisher transformed correlation coefficient.
Time frame: Baseline (week 1) through follow up (week 5)
Population: Results are reported for resting state as task data was not able to be collected as planned and for participants that completed all 5 scans.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neurofeedback | Mean Change in Functional Connectivity Patterns in the Brain | -11.2 Fisher Z-transform corr. coefficient | Standard Deviation 13.4 |
| Control Feedback | Mean Change in Functional Connectivity Patterns in the Brain | 38.7 Fisher Z-transform corr. coefficient | Standard Deviation 67.7 |
Secondary
Mean Opioid Craving Score
This outcome will be measured with the Opioid Craving Scale, a 3-item measure of craving that uses a 0-10 analog scale. Total possible score is 0-30, with higher score indicating more craving.
Time frame: Baseline (week 1) to one month post follow-up (*week 9*)
Population: Results presented here is for participants that have both baseline and follow up data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Neurofeedback | Mean Opioid Craving Score | Baseline | 18.8 score on a scale | Standard Deviation 7.9 |
| Neurofeedback | Mean Opioid Craving Score | Follow up | 23.8 score on a scale | Standard Deviation 5.5 |
| Control Feedback | Mean Opioid Craving Score | Baseline | 16.8 score on a scale | Standard Deviation 7.6 |
| Control Feedback | Mean Opioid Craving Score | Follow up | 16.0 score on a scale | Standard Deviation 4.9 |
Secondary
Negative Affect Mean Score
This outcome will be measured by the Quick Inventory of Depressive Symptomatology. This is a 16-item measure, using a 0-3 scale for each item. Total possible score is 0-48, with higher scores indicating greater symptom severity.
Time frame: Baseline (week 1) to one month post follow-up (week 9)
Population: Results presented here is for participants that have both baseline and follow up data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Neurofeedback | Negative Affect Mean Score | Baseline | 12 score on a scale | Standard Deviation 1.4 |
| Neurofeedback | Negative Affect Mean Score | Follow up | 14.5 score on a scale | Standard Deviation 2.1 |
| Control Feedback | Negative Affect Mean Score | Baseline | 8.7 score on a scale | Standard Deviation 4.9 |
| Control Feedback | Negative Affect Mean Score | Follow up | 6.7 score on a scale | Standard Deviation 2.5 |