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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Withdrawal Symptoms; Craving; Opioid Use Disorder, Moderate; Opioid Use Disorder, Severe; Negative Affectivity
• Intervention / Treatment: Drug: CBOT + TAU; Drug: Sham + TAU

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 190
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Evaristus A Nwulia, MD, MHS; Phone Number: 410-227-2005; Email: enwulia@evonmedics.org
• Study Contact Backup: Name: Maria M Hipolito, MD; Phone Number: 571-241-2766; Email: mhipolito@evonmedics.org

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Recruiting
      • Howard University
      • Contact: Rai
      • Contact: Hipolito
      • Principal Investigator: Tanya N Alim, MD
      • Sub-Investigator: Mark Johnson, MD
    • Washington, District of Columbia, United States, 20002
      • Recruiting
      • Clinics of Dr. Edwin Chapman @ MHDG
      • Contact: Settles-Reaves
      • Contact: Adenuga
      • Principal Investigator: Edwin Chapman, MD
    • Washington, District of Columbia, United States, 20020
      • Recruiting
      • Family and Medical Counseling Service, Inc
      • Contact: Serlin
      • Contact: Jackson
      • Principal Investigator: Michael Serlin, MD
  • Maryland
    • Rockville, Maryland, United States, 20853
      • Recruiting
      • Maryland Treatment Centers @ Avery Road Treatment Center
      • Contact: Wenzel
      • Contact: Machineni

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CBOT + TAU; 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; 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.; Other Names: plant based essential oils
SHAM_COMPARATOR: Sham + TAU; 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; Sham CBOT device uses artificially scented compressed room air instead of olfactory stimulants and has control cognitive tasks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Evon Medics LLC
• Collaborators: National Institute on Drug Abuse (NIDA); Howard University; Family and Medical Counseling Service, Inc; Maryland Treatment Centers @ ARTC; Clinics of Dr. Edwin Chapman, MD, PC @ MHDG
• Investigators: Principal Investigator: Evaristus A Nwulia, MD, Evon Medics LLC; Principal Investigator: Tanya Alim, MD, Howard University; Principal Investigator: Mark Johnson, MD, Howard University; Principal Investigator: Michael Serlin, MD, Family and Medical Counseling Service, Inc; Principal Investigator: Edwin Chapman, MD, Clinics of Dr. Edwin C. Chapman, MD, PC @ MHDG

Publications and helpful links

General Publications

• Jackson C, Rai N, McLean CK, Hipolito MMS, Hamilton FT, Kapetanovic S, Nwulia EA. Overlapping Risky Decision-Making and Olfactory Processing Ability in HIV-Infected Individuals. Clin Exp Psychol. 2017 Sep;3(3):160. doi: 10.4172/2471-2701.1000160. Epub 2017 Aug 15.
• Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex. 2000 Mar;10(3):318-25. doi: 10.1093/cercor/10.3.318.
• Lucantonio F, Takahashi YK, Hoffman AF, Chang CY, Bali-Chaudhary S, Shaham Y, Lupica CR, Schoenbaum G. Orbitofrontal activation restores insight lost after cocaine use. Nat Neurosci. 2014 Aug;17(8):1092-9. doi: 10.1038/nn.3763. Epub 2014 Jul 20. Erratum In: Nat Neurosci. 2014 Sep;17(9):1287.
• Temple DM. Isolation techniques for pharmacologically active substances (animal). Annu Rev Pharmacol. 1969;9:407-18. doi: 10.1146/annurev.pa.09.040169.002203. No abstract available.
• Hummel T, Rissom K, Reden J, Hahner A, Weidenbecher M, Huttenbrink KB. Effects of olfactory training in patients with olfactory loss. Laryngoscope. 2009 Mar;119(3):496-9. doi: 10.1002/lary.20101.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 26, 2021
• Primary Completion (ANTICIPATED): November 30, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (ACTUAL): April 20, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 6, 2021
• Last Update Submitted That Met QC Criteria: July 30, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Relapse Prevention; Opioid Use Disorders; Buprenorphine Maintenance Treatment; Orbitofrontal cortex (OFC); CBOT
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Narcotic-Related Disorders; Substance-Related Disorders; Disease; Opioid-Related Disorders; Substance Withdrawal Syndrome
• Other Study ID Numbers: CBOTDA049616; 2R44DA049616-02 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No