Mindfulness-Oriented Recovery Enhancement (MORE) in Heroin Addiction

Study Overview
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Brief Summary
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In this study, neuroimaging of reward processing, drug cue reactivity and inhibitory control is used before and immediately after 8 weeks of two types of group therapy in individuals with opioid addiction; clinical outcomes will be assessed before, immediately and three months after treatment. Results could point to factors that track and predict recovery with treatment, offering clinicians markers that can be used for enhancing precision medicine with the goal of reducing morbidity and mortality associated with opiate addiction.

Detailed Description
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Over the past 15 years, the US has been affected by increasing prescription and illicit opiate/opioid abuse, addiction, and overdose. Research into the enhancement of treatment options for individuals with opiate/opioid use disorder (iOUD) is clearly a priority. The development of neuroscience-informed behavioral therapies that could be used as adjuncts to improve effectiveness of medication-assisted interventions in iOUD is a national priority, a response to the opiate crisis. This study measures the neural correlates of cognitive function and reward processing as potentially contributing to and predictive of the impact of an 8-week group therapy on addiction outcome in iOUD. Using a pre-post randomized treatment design with a 3-months follow-up, this study will examine the impact of group therapy, as add-on to methadone maintenance, on neural functional and structural plasticity, and clinical outcomes (including daily ecological momentary assessments), in treatment-seeking iOUD (with primary use of heroin). Treatment-seeking iOUD will be randomized to 8-weeks of one of two of group therapies and scanned with magnetic resonance imaging (MRI) immediately before and after treatment. Healthy controls will be scanned at similar time intervals. Clinical outcome will be assessed during, immediately after and 3-months after therapy. Results may help identify individual variability in the brain regions/circuits that support reward processing, including cue reactivity, and inhibitory control and that could change with, and predict, response to treatment, ultimately contributing to precision medicine in OUD.

Official Title
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Neuroimaging Response Inhibition and Salience Attribution Changes During Mindfulness-based Treatment of Human Heroin Addiction

Conditions
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Opiate Use Disorder

Intervention / Treatment
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* Behavioral: Behavioral group therapy #1
* Behavioral: Behavioral group therapy #2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and give informed consent Males and Females 18-64 years of age DSM-5 diagnosis of OUD with heroin as the primary drug of choice Stabilized on methadone or other form of MAT. Inclusion criteria for healthy controls: - The same as inclusion criteria 1-2 above; dependence on nicotine or caffeine is non-exclusionary. Exclusion Criteria: DSM-5 diagnosis for schizophrenia or developmental disorder (e.g., autism) Head trauma with loss of consciousness History of neurological disease of central origin including seizures Cardiovascular disease including high blood pressure and/or other medical conditions, including metabolic, endocrinological,oncological or autoimmune diseases, and infectious diseases common in iOUD including Hepatitis B and C or HIV/AIDS Metal implants or other MR contraindications Exclusion criteria for healthy control subjects: - The same, except history of any drug use disorder is prohibitive.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Individuals with opiate use disorder (iOUD) will be randomized to one of two 8-weeks of group therapy and scanned with magnetic resonance imaging (MRI) immediately before and after treatment. Functional MRI (fMRI) scans during select tasks and at rest will assess responsiveness and connectivity of neural networks underlying impairments in Response Inhibition and Salience Attribution (iRISA). Structural MRI will assess the morphological integrity of the neural networks. A follow-up visit will take place 3 months after the second MRI scan. Healthy controls will be scanned at similar time intervals. Data collected from healthy control subjects will be used for comparative analyses.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Behavioral group therapy 1<br>8-weeks of group therapy | Behavioral: Behavioral group therapy #1<br>* Participants will participate in an 8-weeks of group therapy that uses psychological principles including mindfulness training, and could help decrease cravings for heroin and increase general well-being.<br>|
| Active Comparator: Behavioral group therapy 2<br>8-weeks of group therapy | Behavioral: Behavioral group therapy #2<br>* Participants will participate in an 8-weeks of group therapy that uses psychological principles (but not including mindfulness training) and could help decrease craving for heroin and increase general well-being.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fMRI BOLD signal during tasks of reward | Change in fMRI blood-oxygen-level dependent (BOLD) signal acquired during tasks of reward at the 2nd MRI conducted immediately after the 8-week group therapy (about 3 months after enrollment) as compared to baseline MRI. The reward task uses symbols of gain/win and has been shown to elicit BOLD activations in the brain's reward network. | baseline and 3 months after enrollment | 
| Change in fMRI BOLD signal for control reactivity | Change in fMRI blood-oxygen-level dependent (BOLD) signal acquired during control reactivity at the 2nd MRI conducted immediately after the 8-week group therapy (about 3 months after enrollment) as compared to baseline MRI. | baseline and 3 months enrollment | 
| Change in fMRI BOLD signal for cue reactivity | Change in fMRI blood-oxygen-level dependent (BOLD) signal acquired during cue reactivity at the 2nd MRI conducted immediately after the 8-week group therapy (about 3 months after enrollment) as compared to baseline MRI. | baseline and 3 months enrollment | 
| Change in fMRI BOLD signal acquired during resting-state functional connectivity | Change in fMRI blood-oxygen-level dependent (BOLD) signal acquired during resting-state functional connectivity at the 2nd MRI conducted immediately after the 8-week group therapy (about 3 months after enrollment) as compared to baseline MRI. This method captures the synchronicity of low-frequency, spontaneous fluctuations in blood oxygen level-dependent signals that reflect fluctuations in neuronal activity between brain regions in the absence of external stimulation. | baseline and 3 months after treatment | 
| Change in MRI Voxel-Based Morphometry (VBM) measure | Change in MRI VBM measure for grey matter volume at the 2nd MRI conducted immediately after the 8-week group therapy (about 3 months after enrollment) as compared to baseline MRI. Voxel Based Morphometry is a whole-brain, fully automated, unbiased, MRI analysis technique used to detect regionally specific differences in brain tissue composition using a voxel-wise comparison across participants. | baseline and 3 months after treatment | 
| Change in Urine drug test | Urine drug test at 3 months after treatment as compared to baseline | baseline and 3 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mindfulness, Opiate Use Disorder, Drug Cue Reactivity, Inhibitory Control, Salience Attribution