Olfactory Training for Substance Use Disorders

(EDITOR Trial)

Recruiting at 4 trial locations

Overseen By Opeyemi M Awofeso, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Evon Medics LLC

Must be taking: Buprenorphine, Naltrexone

Disqualifiers: Neurological disease, Serious mental illness, Unstable medical condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new device called EDITOR (Enhanced Digital-Chemosensory-Based Olfactory Training) to aid in treating substance use disorders, such as opioid, stimulant, or alcohol abuse. The goal is to determine if this device, which combines smell and brain training, improves treatment outcomes more effectively than usual care or another similar device. Participants will use the device daily for three months alongside their usual treatment. Suitable candidates for this trial include individuals who have experienced moderate or severe substance use issues in the past three months and are open to trying new treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be willing to receive buprenorphine (for opioid use disorder) or naltrexone (for alcohol use disorder) during the study.

What prior data suggests that the EDITOR device is safe for treating substance use disorders?

Research has shown that the Enhanced Digital-Chemosensory-Based Olfactory Training (EDITOR) device is generally well-tolerated by individuals with substance use disorders. Early results suggest that any side effects are manageable, making it a promising option for those dealing with opioid, stimulant, and alcohol use disorders.

The CBOT device, used as a comparison in some studies, has also been reported to be safe with manageable side effects. Both devices aim to stimulate certain brain areas to help manage substance use disorders.

Since this trial is in an early stage, its main goal is to gather more information on safety and effectiveness before proceeding further. While initial results are positive, the full safety profile is still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Enhanced Digital-Chemosensory-Based Olfactory Training (EDITOR) because it offers a novel approach to treating substance use disorders by targeting the brain's orbitofrontal cortex with chemosensory stimulation. Unlike traditional treatments that often focus on medication or cognitive-behavioral therapy, this method uses a device that combines olfactory stimulation with digital training tasks. The inclusion of beta-caryophyllene is a unique aspect, which is believed to aid in addressing alcohol and stimulant use disorders. Additionally, the digital enhancements enable remote monitoring and data transmission, making the treatment more accessible and personalized.

What evidence suggests that the EDITOR device is effective for substance use disorders?

Research has shown that Enhanced Digital-Chemosensory-Based Olfactory Training (EDITOR), a treatment in this trial, aims to improve brain function related to substance use disorders. This treatment uses smells and mental exercises to increase brain activity, potentially reducing drug cravings and improving treatment outcomes. Although no direct evidence of its effectiveness exists yet, the method relies on enhancing the brain's ability to change and adapt. Studies suggest that another treatment in this trial, Chemosensory-Based Olfactory Training (CBOT), helps people stay in treatment longer and prevents relapses in substance use disorders. Both treatments explore new ways to manage substance abuse by focusing on brain activity and behavior. ^{1 2 3 6 7}

Who Is on the Research Team?

Marc Fishman, MD

Principal Investigator

Maryland Treatment Center

Tanya Alim, MD

Principal Investigator

Howard University

Edwin Chapman, MD

Principal Investigator

Clinics of Dr. Edwin Chapman at MHDG

Evaristus Nwulia, MD

Principal Investigator

Evon Medics LLC

Charles Nwaokobia

Principal Investigator

Evon Medics LLC

Are You a Good Fit for This Trial?

This trial is for adults with substance use disorders, including opioid, methamphetamine, cocaine, and alcohol addiction. Participants will be recruited from community clinics and must be currently receiving treatment.

Inclusion Criteria

Have a stable place to stay and retain the EDITOR devices in a secure condition when receiving the intervention and during the entire duration of the study participation

Diagnosis of current moderate or severe substance use disorders, opioid use disorders, stimulant (cocaine and methamphetamine) use, and alcohol use disorders in the past three months, including the past month

Does not meet criteria for other current SUDs outside of the 3 above, except for mild or moderate use of cannabis

Exclusion Criteria

Known allergies or intolerance to aromas from plant essential oils. E.g., orange and lemon

Breastfeeding or pregnancy test positive or plans to get pregnant in the 6 months following enrollment

Individuals who are on parole or probation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily EDITOR therapy alongside treatment-as-usual (TAU) for three months, involving olfactory stimulation and training tasks.

12 weeks

Daily remote sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including retention and relapse rates.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enhanced Digital-Chemosensory-Based Olfactory Training

Trial Overview The study tests the EDITOR device—a digital-chemosensory olfactory training tool—against standard treatments and a control CBOT device. It aims to see if EDITOR can improve patient outcomes like staying in treatment longer and maintaining abstinence.

How Is the Trial Designed?

Group I: Enhanced Digital-Chemosensory-Based Olfactory Training (EDITOR) Experimental Treatment 1 Intervention

The EDITOR device is designed to stimulate intensive neural activity in OFC over long periods of time. It consists of 40 daily cycles of intervention with a combination of olfactory stimulation and training tasks, lasting \~45 minutes, delivered once daily over three months. The device also includes 60% beta-caryophyllene chemosensory stimulation to target AUD and stimulant use disorder and 10 digital enhancements for the purpose of remote treatment, remote acquisition of behavioral and physiological data, and seamless data transmission to providers, through a HIPAA-compliant clinic end portal. Participants assigned to this arm will receive their treatment-as-usual (TAU) alongside daily EDITOR therapy for three months. TAU will depend on the drug abused \[Buprenorphine with a median dose of 24 mg (range 16 - 32 mg) for Opioid use disorder and naltrexone (50-100 mg daily for Alcohol use disorder (AUD).

Group II: Chemosensory-Based Olfactory Training (CBOT) Active Control 1 Intervention

CBOT with olfactory stimulants \& orbitofrontal (OFC) tasks TAU same as above + CBOT (Chemosensory-Based Olfactory Training) therapy (40 cycles of olfactory stimulation and OFC training tasks, lasting \~45 minutes, once daily over three months) + use of their smartphone to communicate with their clinic provider/staff

Group III: Chemosensory-Based Olfactory Training (CBOT) Sham Placebo Group 1 Intervention

Control Device (Sham) is CBOT device without olfactory stimulants and orbitofrontal tasks. TAU same as above + CBOT sham + use of their smartphone to communicate with their clinic provider/staff. This CBOT device uses compressed room air scented with phenylethylamine (rose scent) instead of olfactory stimulants and has shape pattern matching tasks instead of cognitive tasks in order to blind users to their treatment assignment. Similar to the active arm, sham COT will be used daily for 45 minutes.

Who Is Running the Clinical Trial?

Evon Medics LLC

Lead Sponsor

Trials

5

Recruited

1,000+

Howard University

Collaborator

Trials

44

Recruited

15,200+

Maryland Treatment Center

Collaborator

Trials

1

Recruited

300+

Clinics of Dr. Edwin Chapman, MD, PC @ MHDG

Collaborator

Trials

2

Recruited

490+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The vertebrate olfactory system uses a diverse set of G protein-coupled receptors, which make up about 1% of vertebrate genes, to recognize and differentiate a wide range of odors.

Recent studies have shown that odorant receptors can recognize multiple related odorants and that odor discrimination relies on a combinatorial code, where different receptors work together to identify specific smells, with this coding changing based on odor concentration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odor discrimination by G protein-coupled olfactory receptors. Touhara, K.[2016]

The study of 156 individuals aged 18-25 revealed that olfactory abnormalities are linked to substance addiction, showing that these changes can predict earlier substance use and are associated with immune system issues.

Episodic users of substances exhibited reduced aversive reactions to certain odors, which correlated with signs of immune deficiency and increased cortisol levels, suggesting that olfactory testing could be a useful tool in understanding and predicting addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Association between pathological olfaction, immunological abnormalities and predisposition to substance use]. Nevidimova, TI., Batukhtina, EI., Savochkina, DN., et al.[2018]

The study developed a neuroimaging-guided approach to noninvasive brain stimulation (NIBS) targeting the cerebellar cortex and prefrontal cortex, showing that cerebellar tDCS can induce significant gamma oscillations in the cerebral cortex, which may help in addressing cue-reactivity in cannabis use disorder.

A preliminary study with 10 healthy participants demonstrated that cerebellar tDCS effectively increased oxyhemoglobin levels in both the cerebellum and prefrontal cortex, indicating the potential for NIBS to enhance cognitive functions related to substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Portable Neuroimaging-Guided Noninvasive Brain Stimulation of the Cortico-Cerebello-Thalamo-Cortical Loop-Hypothesis and Theory in Cannabis Use Disorder. Walia, P., Ghosh, A., Singh, S., et al.[2022]

Olfactory dysfunction can be an early indicator of various neurodegenerative and neuropsychiatric disorders, highlighting the importance of the olfactory system in understanding neuromodulation.

The endocannabinoid system interacts with olfactory processing, and recent advances in understanding its receptor dynamics may lead to new therapeutic drugs for conditions like neuroinflammation and neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocannabinoid-mediated neuromodulation in the main olfactory bulb at the interface of environmental stimuli and central neural processing. Heinbockel, T., Bhatia-Dey, N., Shields, VDC.[2022]

In a study involving 24 short-term abstinent heroin-dependent patients and 20 drug-naïve individuals, exposure to heroin-related cues significantly increased craving levels in the heroin-dependent group.

Neuroimaging revealed that this craving was associated with heightened activation in key brain areas related to reward and decision-making, such as the nucleus accumbens and prefrontal cortex, indicating a strong neural basis for the vulnerability to relapse in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: an event-related fMRI study. Li, Q., Wang, Y., Zhang, Y., et al.[2021]

Rodent models of addiction have provided valuable insights into the mechanisms of drug-related behaviors, particularly highlighting the role of glutamatergic synaptic transmission and mesolimbic dopamine activation in addiction.

Using advanced techniques like optogenetics, researchers can manipulate specific brain circuits to reverse drug-induced changes, paving the way for new treatment options such as deep brain stimulation for addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Emergence of a Circuit Model for Addiction. Lüscher, C.[2018]

Addiction is a chronic disease characterized by compulsive drug-seeking behavior, which can lead to long-lasting changes in the brain's structure and function, particularly in the mesolimbic dopamine system.

Current research is focused on understanding the specific neural pathways involved in addiction and how alterations in brain regions and synaptic connections contribute to the disease, which is essential for developing effective medical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological substrates of addiction. Joffe, ME., Grueter, CA., Grueter, BA.[2021]

The cannabinoid type-1 (CB1) receptor is present in various olfactory brain areas and plays a significant role in how olfactory information is processed and influences behavior.

Recent research has begun to uncover the specific cellular mechanisms by which cannabinoid signaling affects olfactory processing, highlighting the importance of the endocannabinoid system in regulating olfactory circuits and related behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoid Control of Olfactory Processes: The Where Matters. Terral, G., Marsicano, G., Grandes, P., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06434818

Enhanced Digital-Chemosensory-Based Olfactory Training ... This enhances neurobehavioral plasticity, benefiting Substance Use Disorder (SUD) outcomes. The device also features a 60% beta-caryophyllene scent for ...

2. reporter.nih.gov reporter.nih.gov/search/Au2AYliZFkKjTRmE-WlMfQ/project-details/10873840

Project Details ABSTRACT The Development and Evaluation of Enhanced Digital-Chemosensory-Based Olfactory Training for Remote Management of Substance Use Disorders (EDITOR) ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06434818/enhanced-digital-chemosensory-based-olfactory-training-for-remote-management-of-substance-use-disorders

Enhanced Digital-Chemosensory-Based Olfactory Training for ... The overarching goal of this study phase, Phase II component is to implement Enhanced Digital-Chemosensory-Based Olfactory Training for Remote Management of ...

4. withpower.com withpower.com/trial/phase-2-opioid-related-disorders-6-2023-21359

Olfactory Training for Substance Use Disorders Episodic users of substances exhibited reduced aversive reactions to certain odors, which correlated with signs of immune deficiency and increased cortisol ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04850664

Computerized Chemosensory-Based Orbitofrontal Cortex ... 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; ...

6. clinconnect.io clinconnect.io/trials/NCT06434818

Enhanced Digital-Chemosensory-Based Olfactory Training The goal is to see if using the EDITOR device in treatment clinics leads to better outcomes for patients compared to standard treatment or another device called ...

7. wp4r.trialstoday.org wp4r.trialstoday.org/trial/NCT06434818

Enhanced Digital-Chemosensory-Based Olfactory Training ... The investigators will conduct a multi-site study of 300 adult patients with opiate use disorder (OUD), stimulant (i.e., cocaine, ...