Opioid Addiction
Conditions
Brief summary
This study proposes to use functional magnetic resonance imaging (FMRI) to observe brain activity and behavior associated with decision-making about rewards (DD task), working memory and working memory cognitive persistence (WM task), and craving (CR task) in 72 opiate dependent participants initiating buprenorphine. While stably using opiates (initial study appointment) and again during withdrawal (approximately 3 days later), participants will receive an FMRI scan with behavioral challenges; immediately after the second FMRI, they will receive their first dose of buprenorphine. Buprenorphine treatment will continue for twelve weeks, followed by a four week taper. Urine toxicological analysis will be performed prior to the first scanning session, weekly for two weeks and biweekly thereafter. Participation for all individuals will last 4 months. Assessments will occur at baseline, and weeks 1, 2, 4, 8, and 12. Buprenorphine induction will begin at the completion of the second scan; follow-up medical visits will align with study assessments on weeks 1, 2, 4, 8 and 12. All participants will receive 16 weeks of buprenorphine (the final 4 of these 16 weeks will include a taper).
Interventions
OTHERFMRI
all participants will complete 2 FMRIs
DRUGSuboxone
all participants will be prescribed Suboxone for 4 months during their study participation
Sponsors
Butler Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* opiate dependent persons * 21-50 years old * interested in initiating outpatient buprenorphine treatment
Exclusion criteria
* current methadone maintenance treatment program participation * medically necessary prescription opiate treatment (e.g., for chronic pain) * current criteria for a DSM-V diagnosis of substance dependence for sedative or hypnotic drugs, alcohol, stimulants, cocaine, inhalants, hallucinogens * diagnosis of organic brain disorder, bipolar disorder, schizophrenia, schizo-affective, schizophreniform or paranoid disorder * current suicidality on the Modified Scale for Suicidal Ideation * evidence of neuropsychological dysfunction as assessed by the study physician with confirmation with the Folstein Mini-Mental Status Examination• * anticipated major painful event (significant surgical procedure) in the coming 4 months * probation or parole requirements or an upcoming move that might interfere with protocol participation * history of allergic reaction to buprenorphine or naloxone * currently pregnant or planning to become pregnant in the next 4 months * history of neurological disorder (e.g., epilepsy, stroke, brain injury) * impaired uncorrected vision * FMRI contraindications (e.g., claustrophobia, specific metallic implants and injuries)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Resting State Disorganization Between Baseline and One Week by Person by Lapsed Category | Baseline and 1 week | The measure of resting state organization is a z-value derived from Pearson's r-values. They represent the effect of the association between the brain activity of the seed region and each brain voxel over time during the resting state FMRI scan. A central z-value of 0 means that there is no association between the seed region and the voxel. Positive and negative z-values approaching 0 reflect increasingly weaker associations, and more extreme positive and negative values reflect stronger associations. Attributing the qualitative labels better or worse to these values depend upon the brain network and context. In many networks (eg, task-positive cognitive control network), a stronger positive correlation is thought to reflect better network organization. In the task-negative default mode network a stronger positive relationship is considered by some as worse. For this study, these are not yet used as clinical measures and there are not known cutoffs. |
| Working Memory - Between Groups at Baseline by Lapsed Category | Baseline | fMRI working memory differences between participants who lapse back to opioid use and those who don't |
| Changes in Working Memory - Within Groups During Satiation and Withdrawal | Baseline and 1 week | fMRI working memory differences under satiation vs withdrawal from opioids |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants FMRI Suboxone
FMRI: all participants will complete 2 FMRIs
Suboxone: all participants will be prescribed Suboxone for 4 months during their study participation | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | did not attend second fMRI | 1 |
| Overall Study | ruled out at screening | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 36.63 years STANDARD_DEVIATION 7.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 7 |
| other Total, other adverse events | 0 / 12 | 0 / 7 |
| serious Total, serious adverse events | 0 / 12 | 0 / 7 |
Outcome results
Primary
Changes in Resting State Disorganization Between Baseline and One Week by Person by Lapsed Category
The measure of resting state organization is a z-value derived from Pearson's r-values. They represent the effect of the association between the brain activity of the seed region and each brain voxel over time during the resting state FMRI scan. A central z-value of 0 means that there is no association between the seed region and the voxel. Positive and negative z-values approaching 0 reflect increasingly weaker associations, and more extreme positive and negative values reflect stronger associations. Attributing the qualitative labels better or worse to these values depend upon the brain network and context. In many networks (eg, task-positive cognitive control network), a stronger positive correlation is thought to reflect better network organization. In the task-negative default mode network a stronger positive relationship is considered by some as worse. For this study, these are not yet used as clinical measures and there are not known cutoffs.
Time frame: Baseline and 1 week
Population: Mean fMRI resting state disorganization at baseline among no-lapse and lapse groups
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Lapse | Changes in Resting State Disorganization Between Baseline and One Week by Person by Lapsed Category | DMN synchrony active use | 0.315 Mean default mode network (DMN) z-scores | Standard Deviation 0.057 |
| No Lapse | Changes in Resting State Disorganization Between Baseline and One Week by Person by Lapsed Category | DMN synchrony abstinent | 0.384 Mean default mode network (DMN) z-scores | Standard Deviation 0.098 |
| Lapse | Changes in Resting State Disorganization Between Baseline and One Week by Person by Lapsed Category | DMN synchrony active use | 0.328 Mean default mode network (DMN) z-scores | Standard Deviation 0.076 |
| Lapse | Changes in Resting State Disorganization Between Baseline and One Week by Person by Lapsed Category | DMN synchrony abstinent | 0.394 Mean default mode network (DMN) z-scores | Standard Deviation 0.139 |
Primary
Changes in Working Memory - Within Groups During Satiation and Withdrawal
fMRI working memory differences under satiation vs withdrawal from opioids
Time frame: Baseline and 1 week
Population: Within-group analyses contrasting two fMRI responses
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in R middle frontal gyrus | 0.35 % fMRI signal change | Standard Deviation 0.3 |
| No Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in R inferior parietal lobule | 0.33 % fMRI signal change | Standard Deviation 0.29 |
| No Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in L inferior parietal lobule | 0.47 % fMRI signal change | Standard Deviation 0.43 |
| No Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in bilateral supplementary motor | 0.34 % fMRI signal change | Standard Deviation 0.27 |
| Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in bilateral supplementary motor | 0.35 % fMRI signal change | Standard Deviation 0.22 |
| Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in R middle frontal gyrus | 0.37 % fMRI signal change | Standard Deviation 0.25 |
| Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in L inferior parietal lobule | 0.54 % fMRI signal change | Standard Deviation 0.32 |
| Lapse | Changes in Working Memory - Within Groups During Satiation and Withdrawal | Mean Brain Response in R inferior parietal lobule | 0.42 % fMRI signal change | Standard Deviation 0.22 |
Primary
Working Memory - Between Groups at Baseline by Lapsed Category
fMRI working memory differences between participants who lapse back to opioid use and those who don't
Time frame: Baseline
Population: Mean fMRI working memory response at baseline among no-lapse and lapse groups
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L middle frontal gyrus (c) | 0.39 % fMRI signal change | Standard Deviation 0.22 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | bilateral SMA | 0.45 % fMRI signal change | Standard Deviation 0.14 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | R middle frontal gyrus | 0.39 % fMRI signal change | Standard Deviation 0.15 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | R inferior parietal lobule | 0.34 % fMRI signal change | Standard Deviation 0.14 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L inferior parietal lobule | 0.36 % fMRI signal change | Standard Deviation 0.14 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L middle frontal gyrus (a) | 0.46 % fMRI signal change | Standard Deviation 0.2 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L middle frontal gyrus (b) | 0.36 % fMRI signal change | Standard Deviation 0.16 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | bilateral precuneus | 0.38 % fMRI signal change | Standard Deviation 0.2 |
| No Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | R anterior insula | 0.42 % fMRI signal change | Standard Deviation 0.14 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | R anterior insula | 0.39 % fMRI signal change | Standard Deviation 0.26 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L middle frontal gyrus (a) | 0.49 % fMRI signal change | Standard Deviation 0.26 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | bilateral SMA | 0.42 % fMRI signal change | Standard Deviation 0.27 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | bilateral precuneus | 0.37 % fMRI signal change | Standard Deviation 0.26 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | R middle frontal gyrus | 0.40 % fMRI signal change | Standard Deviation 0.23 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L middle frontal gyrus (b) | 0.33 % fMRI signal change | Standard Deviation 0.25 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | R inferior parietal lobule | 0.33 % fMRI signal change | Standard Deviation 0.24 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L middle frontal gyrus (c) | 0.36 % fMRI signal change | Standard Deviation 0.28 |
| Lapse | Working Memory - Between Groups at Baseline by Lapsed Category | L inferior parietal lobule | 0.32 % fMRI signal change | Standard Deviation 0.25 |