Computerized Chemosensory-Based Orbitofrontal Cortex (CBOT) for Opioid Use Disorder

Study Overview
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Brief Summary
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Opioid Use Disorders (OUD) cause significant burden to individuals, families, and the society. Our product - Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) - offers a cost-saving, home-based, user-friendly brain stimulation system that increased 6-month treatment retention of OUDs in a pilot study; and also, acutely reduced opioid withdrawal severity and negative affect during induction into opioid maintenance therapy. This study will establish its effectiveness in a broad category of OUD subjects at different stages of OUD care continuum.

Detailed Description
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Evon Medics proposes to evaluate the effectiveness of Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT), as an alternative strategy for relapse prevention in patients with Opioid Use (OUD) and other substance use disorders (SUD). This treatment leverages the overlap in brain regions that process smell and mediate decision making. The CBOT is portable and can be used at home. This clinical trial is being conducted to demonstrate its utility for home application by nontreatment seeking and treatment-seeking OUD populations, to engage in long-term, successful opioid recovery. Key objectives of this project are to: (1) establish the effectiveness of CBOT for improved retention and relapse prevention in a large sample of OUD subjects; (2) establish its effectiveness for acute reduction of withdrawal severity and negative affect early in recovery; and (3) evaluate its safety, user-friendliness and acceptability. Accomplishment of these goals would lead to larger clinical trials for OUD and wider applications of CBOT in other addictive disorders.

Official Title
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Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) for Opioid Use Disorder

Conditions
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Craving, Opioid Use Disorder, Moderate, Opioid Use Disorder, Severe, Withdrawal Symptoms, Negative Affectivity

Intervention / Treatment
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* Drug: CBOT + TAU
* Drug: Sham + TAU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18- 70years Diagnosis of current moderate or severe OUD in the past 6 months, including the past one month Willing to receive study interventions and buprenorphine during the study Do not meet criteria for current moderate or severe use of other substance use disorders (except nicotine use disorder) Diagnosis of Major Depressive Disorder, Anxiety disorders, and Post-traumatic Stress disorders will be included as long as the symptoms are stable, no suicidal ideas or plans and there are no recent changes in treatment of these conditions in the last 6 weeks prior to enrollment No intranasal disease Willing to participate by signing the informed consent form and Have a place to stay when receiving the intervention. Exclusion Criteria: Any significant neurologic disease such as stroke, dementia, meningitis, neurosyphilis, cerebral palsy, encephalitis, epilepsy or seizures Mental retardation Schizophrenia or bipolar disorders Experiencing current suicide ideas or plans Any unstable medical condition such as uncontrolled hypertension, uncontrolled diabetes, and liver cirrhosis, as determined by site PI History of severe traumatic nose injury that affects ability to smell, as determined by site PI Allergies or intolerance to aromas from plant essential oils (e.g. orange and lemon) Breastfeeding or Pregnancy test positive. On parole or probation mandated to receive treatment for OUD.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Evon Medics will perform randomization of participants stratified by sex at site level. Site staff and participants will be blinded to treatment assignment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBOT + TAU<br>CBOT consists of 40 cycles of olfactory stimulation and OFC training tasks, lasting  45 minutes, once daily over 3 months. Treatment-as-usual (TAU) is standard dosing of buprenorphine (BUP) to a median dose of 24 mg (range 16-32 mg). | Drug: CBOT + TAU<br>* The CBOT with proprietary odorant molecules is designed to stimulate olfactory neural activity over long periods of time. It is paired with OFC-dependent cognitive tasks.<br>* Other names: plant based essential oils;|
| Sham Comparator: Sham + TAU<br>Sham is a CBOT device that uses artificially-scented compressed room air instead of olfactory stimulants and has no OFC cognitive tasks. Similar to the CBOT, sham will be used daily for 45 minutes. TAU is standard dosing of buprenorphine (BUP) to a median dose of 24 mg (range 16-32 mg). | Drug: Sham + TAU<br>* Sham CBOT device uses artificially scented compressed room air instead of olfactory stimulants and has control cognitive tasks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 2 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 4 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 6 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 8 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 10 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 12 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 14 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 16 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 18 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 20 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 22 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 24 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 26 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 28 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 30 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 32 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 34 weeks after baseline | 
| 6-month buprenorphine maintenance treatment (BMT) retention | 6-month BMT retention is defined as missing two consecutive clinic visits after completing the first two weeks of BMT treatment, to allow for BUP dose stabilization. Ascertainment of retention is simply by tracking clinic visits and electronic record of the health visit. | 36 weeks after baseline | 
| Change from Screening in Subjective Opiate Withdrawal Scale (SOWS) at week | The SOWS is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely), and takes less than 10 minutes to complete. | Screening to Week 12 Treatment | 
| Change from Screening in Subjective Opiate Withdrawal Scale (SOWS) at Week 24 | The SOWS is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely), and takes less than 10 minutes to complete. | Screening to Week 24 | 
| Change from Screening in Opioid Craving Scale (OCS) at Week 12 severity rating measures over 1 month | he Opioid Craving Scale, a modification of the Cocaine Craving Scale was used to measure opioid craving. | Screening visit to Week 12 | 
| Change from Screening in Opioid Craving Scale (OCS) at Week 24 severity rating measures over 1 month | he Opioid Craving Scale, a modification of the Cocaine Craving Scale was used to measure opioid craving. | Screening visit to Week 24 | 
| Change from Screening in negative affect severity in the PANAS | The Positive and Negative Affect Schedule (PANAS) is the most widely and frequently used scale to assess positive and negative affect. | Screening visit to Week 12 | 
| Change from Screening in negative affect severity in the PANAS | The Positive and Negative Affect Schedule (PANAS) is the most widely and frequently used scale to assess positive and negative affect. | Screening visit to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Relapse | Relapse is defined as presence of self-reported repeated (i.e. 2 or more) use after the first two weeks for stabilization of buprenorphine dose, and/or presence of positive urine drug test for opiates. Ascertainment of opioid relapse is through: (a) Survey question administered 2-weekly, inquiring how days in the past did the subject use heroin, prescription opiates and/or other drugs; the dates of drug use; and the quantity (or dose) of drugs used; and (b) Biochemical verification of drug use, through urine samples will be collected and tested every two weeks. | Screening visit to Week 12 | 
| Pre-Intervention changes in SOWS from Screening at Week 2 | The SOWS is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). | Screening visit to Week 2 | 
| Post-Intervention changes in SOWS from Week 12 at Week 13 | The SOWS is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). | Week 12 to Week 13 | 
| Pre-Intervention changes in OCS from Screening to Week 2 | a modification of the Cocaine Craving Scale was used to measure opioid craving. | Screening visit to Week 2 | 
| Post-Intervention changes in OCS from Week 12 to Week 13 | a modification of the Cocaine Craving Scale was used to measure opioid craving. | Week 12 to Week 13 | 
| Pre-Intervention changes in PANAS negative affect from Screening visit to Week 2 | The Positive and Negative Affect Schedule (PANAS) is the most widely and frequently used scale to assess positive and negative affect. | Screening visit to Week 2 | 
| Post-Intervention changes in PANAS negative affect from Week 12 at Week 13 | The SOWS is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). The Positive and Negative Affect Schedule (PANAS) is the most widely and frequently used scale to assess positive and negative affect. | Week 12 to Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid Use Disorders, Buprenorphine Maintenance Treatment, Orbitofrontal cortex (OFC), CBOT, Relapse Prevention