Neuroimaging Predictors of Relapse During Treatment for Opiate Dependence

• Sponsor: Butler Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02696096
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Actual Duration (Months): 42
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Opioid Addiction	Other: FMRI; Drug: Suboxone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Neuroimaging Predictors of Relapse During Treatment for Opiate Dependence
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Feb 1, 2020
• Actual Study Completion Date: Feb 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: All Participants FMRI Suboxone	Other: FMRI; all participants will complete 2 FMRIs; Other Names: functional magnetic resonance imaging ; Drug: Suboxone; all participants will be prescribed Suboxone for 4 months during their study participation; Other Names: buprenorphine

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

3. Changes in Working Memory - Within Groups During Satiation and Withdrawal [Baseline and 1 week]

   fMRI working memory differences under satiation vs withdrawal from opioids

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Butler Hospital	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• Butler Hospital

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 22, 2017
• Statistical Analysis Plan - Jun 22, 2017

More Information

Publications

None provided.

• Responsible Party: Michael Stein, MD, Principle Investigator, Butler Hospital
• ClinicalTrials.gov Identifier: NCT02696096
• Other Study ID Numbers: 793387
• First Posted: Mar 2, 2016
• Last Update Posted: Aug 17, 2022
• Last Verified: Jul 1, 2022

• Additional relevant MeSH terms: Opioid-Related Disorders; Buprenorphine; Buprenorphine, Naloxone Drug Combination

Study Results

Participant Flow

Arm/Group Title	Participants Who Used Illicit Opioids and Were Interested in Transitioning to Buprenorphine
Arm/Group Description	All participants completed 2 fMRI's and induction on Buprenorphine during the baseline enrollment. Participants were provided Buprenorphine and completed assessments for 4 months. Opioid abstinence was monitored through self-report and urine toxicology during the study period.
Period Title: Overall Study
STARTED	21
Opioid Abstinence During Study Period	11
COMPLETED	19
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	FMRI Suboxone FMRI: all participants will complete 2 FMRIs Suboxone: all participants will be prescribed Suboxone for 4 months during their study participation
Overall Participants	19
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	19 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.63 (7.05)
Sex: Female, Male (Count of Participants)
Female	7 36.8%
Male	12 63.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 15.8%
Not Hispanic or Latino	16 84.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 5.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 10.5%
White	14 73.7%
More than one race	0 0%
Unknown or Not Reported	2 10.5%
Region of Enrollment (Count of Participants)
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Resting State Disorganization Between Baseline and One Week by Person by Lapsed Category
Description	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

Outcome Measure Data

Analysis Population Description

Mean fMRI resting state disorganization at baseline among no-lapse and lapse groups

Arm/Group Title	No Lapse	Lapse
Arm/Group Description	No opioid use during the study period	Opioid use during the study period
Measure Participants	6	5
DMN synchrony active use	0.315 (0.057)	0.328 (0.076)
DMN synchrony abstinent	0.384 (0.098)	0.394 (0.139)

2. Primary Outcome

Title	Working Memory - Between Groups at Baseline by Lapsed Category
Description	fMRI working memory differences between participants who lapse back to opioid use and those who don't
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Mean fMRI working memory response at baseline among no-lapse and lapse groups

Arm/Group Title	No Lapse	Lapse
Arm/Group Description	No opioid use during the study period	Opioid use during the study period
Measure Participants	9	7
bilateral SMA	0.45 (0.14)	0.42 (0.27)
R middle frontal gyrus	0.39 (0.15)	0.40 (0.23)
R inferior parietal lobule	0.34 (0.14)	0.33 (0.24)
L inferior parietal lobule	0.36 (0.14)	0.32 (0.25)
L middle frontal gyrus (a)	0.46 (0.20)	0.49 (0.26)
L middle frontal gyrus (b)	0.36 (0.16)	0.33 (0.25)
L middle frontal gyrus (c)	0.39 (0.22)	0.36 (0.28)
bilateral precuneus	0.38 (0.20)	0.37 (0.26)
R anterior insula	0.42 (0.14)	0.39 (0.26)

3. Primary Outcome

Title	Changes in Working Memory - Within Groups During Satiation and Withdrawal
Description	fMRI working memory differences under satiation vs withdrawal from opioids
Time Frame	Baseline and 1 week

Outcome Measure Data

Analysis Population Description

Within-group analyses contrasting two fMRI responses

Arm/Group Title	fMRI During Withdrawal	fMRI During Opioid Use
Arm/Group Description	this fMRI was completed when the participants were experiencing opioid withdrawal symptoms	this fMRI was completed while participants were satiated with opioids
Measure Participants	12	12
Mean Brain Response in R middle frontal gyrus	0.35 (0.30)	0.37 (0.25)
Mean Brain Response in R inferior parietal lobule	0.33 (0.29)	0.42 (0.22)
Mean Brain Response in L inferior parietal lobule	0.47 (0.43)	0.54 (0.32)
Mean Brain Response in bilateral supplementary motor	0.34 (0.27)	0.35 (0.22)

Adverse Events

Time Frame	4 months
Adverse Event Reporting Description	Adverse events were as noted in clinicaltrials.gov
Arm/Group Title	No Lapse		Lapse
Arm/Group Description	No opioid use during the study period		Opioid use during the study period
All Cause Mortality
	No Lapse		Lapse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/7 (0%)
Serious Adverse Events
	No Lapse		Lapse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	No Lapse		Lapse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.