Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain (CBOT-P)

NCT06671132 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CBOTP2NS1257454R44NS125745-02
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 2

Brief Summary

The overarching goal of this study phase, Phase II component is to perform a randomized clinical trial of the refined Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain \[CBOT-Pain (or CBOT-P)\] from Phase I, compared to sham Computerized Chemosensory-Based Orbitofrontal Networks Training (CBOT) in Chronic Low Back Pain (CLBP) to determine its short- and long-term effectiveness on Pain, Negative Affect (NA), Cognition and Cortical Brain Structure (PACS), long-term safety, and indications. The investigators will perform a randomized clinical trial of the refined CBOT-P from Phase I, compared to sham CBOT in CLBP. Aim 2.1: To determine if CBOT-P significantly influences: (1) acute and long-term reduction of pain severity, and (2) acute and long-term reduction of negative affect. The hypothesis is that optimized CBOT will produce faster, stronger, and longer-lasting improvements in pain severity, NA severity, cognitive impairments, and sleep and functional outcomes. Aim 2.2 To determine if CBOT-P significantly prevents or reduces progressive shrinkage in the orbitofrontal cortex (OFC), cingulate cortex, and hippocampus. MRI will be acquired at baseline and 6th month. An integrative analysis will be conducted to determine the link between changes in brain structure and cognitive trajectory. The hypothesis is that the CBOT optimized with BCP significantly attenuates shrinkage in OFC and other prefrontal cortex (PFC) regions, compared to the Sham intervention.

Conditions

Chronic Pain; Low Back Pain

Keywords

Chronic pain; Pain; Negative Affect; Cognitive Impairments; Attenuation of Structural Brain Loss in CP with high NA; PACS outcome; Orbitofrontal Cortex; Chemosensory-Based Orbitofrontal Networks Training

Outcome Measures

Primary Outcomes (7)

• Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity (Aim 2.1)

  Change in 11-point score PROMIS Numeric Rating Scale v1.0 - Pain Intensity from baseline. The Numeric Rating Scale measures each consist of a single item rating pain on average over the past 7 days from 0 (no pain) to 10 (worst pain).

  Baseline to month 1 visit

• Positive and Negative Affect Schedule (PANAS) rating scale (Aim 2.1)

  Change in negative affect score from the PANAS rating scale It consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a 5-point scale of 1 (not at all) to 5 (very much). Positive Affect Scores can range from 10 - 50, with higher scores representing higher levels of positive affect. Negative Affect Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.

  Baseline to month 1 visit

• Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity (Aim 2.1)

  Change in 11-point score PROMIS Numeric Rating Scale v1.0 - Pain Intensity from baseline. The Numeric Rating Scale measures each consist of a single item rating pain on average over the past 7 days from 0 (no pain) to 10 (worst pain).

  Baseline to month 3 visit

• Positive and Negative Affect Schedule (PANAS) rating scale (Aim 2.1)

  Change in negative affect score from the PANAS rating scale It consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a 5-point scale of 1 (not at all) to 5 (very much). Positive Affect Scores can range from 10 - 50, with higher scores representing higher levels of positive affect. Negative Affect Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.

  Baseline to month 3 visit

• Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity (Aim 2.1)

  Change in 11-point score PROMIS Numeric Rating Scale v1.0 - Pain Intensity from baseline. The Numeric Rating Scale measures each consist of a single item rating pain on average over the past 7 days from 0 (no pain) to 10 (worst pain).

  Baseline to month 6 visit

• Positive and Negative Affect Schedule (PANAS) rating scale (Aim 2.1)

  Change in negative affect score from the PANAS rating scale It consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a 5-point scale of 1 (not at all) to 5 (very much). Positive Affect Scores can range from 10 - 50, with higher scores representing higher levels of positive affect. Negative Affect Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.

  Baseline to month 6 visit

• Grey Matter Volumes of OrbitoFrontal Cortex and Hippocampus Aim 2.2

  Change in the structural brain MRI baseline grey matter volumes of the orbitofrontal cortex and hippocampus at 6 months. The investigators will use linear mixed effect and coefficient measures, and include sex, age, opioid medications, and duration of CP as confounders and as effect modifiers. Investigators will also estimate linear and non-linear trajectories.

  Baseline and 6 months

Secondary Outcomes (31)

• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.1 - Pain Interference scores. Aim 2.1

  Baseline to month 1 visit

• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Anxiety scores Aim 2.1

  Baseline to month 1 visit

• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Sleep Disturbance scores Aim 2.1

  Baseline to month 1 visit

• Total Sleep Time (TST) Centrepoint Insight Actigraph watch Sleep Parameters Aim 2.1

  Baseline and 1 month

• Sleep Onset Latency (SOL) Centrepoint Insight Actigraph watch Sleep Parameters Aim 2.1

  Baseline and 1 month

Study Arms (2)

CBOT-P [CBOT + beta caryophyllene (BCP)]

EXPERIMENTAL

CBOT device with BCP

Combination Product: Computerized Chemosensory-Based Orbitofrontal Cortex Training for Pain

Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT)

SHAM COMPARATOR

CBOT device

Combination Product: Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT)

Interventions

Computerized Chemosensory-Based Orbitofrontal Cortex Training for Pain COMBINATION_PRODUCT

CBOT device with beta-caryophyllene

Also known as: CBOT-P, CBOT device with BCP

CBOT-P [CBOT + beta caryophyllene (BCP)]

Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) COMBINATION_PRODUCT

CBOT device administering continuous olfactoy stimuli with no BCP

Also known as: CBOT device

Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-85.
• Pain duration \> 6 months.
• Must meet the minimum criteria for cognitive function using the PROMIS 4-item cognitive screener \>3.
• Average pain score of \> 5/10, with low back pain being the primary pain site. (5) CLBP (chronic low back pain) meeting Quebec Task Force Classification System Categories I-III.
• (6) Evidence of a prior lumbar spine X-ray to rule out red flags, such as infection, tumor, or fracture.
• (7) For those taking opioids (the opioid subgroup), participants must be prescribed opioids currently for at least 3 consecutive months prior to enrollment. Such patients must be on opioids for a minimum of three months, taking them daily or intermittently during the week. (8) Subject must agree that opioids cannot be increased during the study. (9) No substance use disorder (SUD), except tobacco in the past year based on substance screening survey and frequent urine toxicology screens. (10) No acute suicidality, mania, or psychosis. This will be assessed at study entry, which will also include a review of history in the EHR, Diagnostic Interview for Genetic Studies (DIGS) and Columbia Suicide Severity Rating scale (C-SSRS) and (11) Finally, participants must sign IRB-approved consent.

You may not qualify if:

• Back surgery within the past six months.
• Active worker's compensation or litigation claims.
• New pain and/or psychiatric treatments within 2 weeks of enrollment.
• Intent to add new or increase pain treatments during the study period, such as back surgery, nerve block procedures, or medications.
• Intent to add new psychiatric treatments during the first 3 months of the study.
• Any clinically unstable systemic illness that is judged to interfere with the trial.
• History of cardiac, nervous system, or respiratory disease that, in the investigator's judgment, precludes participation in the study because of a heightened potential for respiratory depression.
• Non-ambulatory status.
• Pregnancy or the intent to become pregnant during the study. Women of childbearing age will have urine pregnancy testing at enrollment and monthly. (10) Anosmia or significant nasal disease
• (11) Contraindications to MRI (12) Stroke or TBI (traumatic brain injury).

Sponsors & Collaborators

• Evon Medics LLC: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Howard University: collaborator
• Global Pain Management, LLC: collaborator
• Georgetown University: collaborator
• University of Maryland: collaborator
• Johns Hopkins University: collaborator
• Family and Medical Counseling Service, Inc: collaborator

Study Sites (2)

Howard University

Washington D.C., District of Columbia, 20060, United States

RECRUITING

Global Pain Management LLC

Pasadena, Maryland, 21112, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain; Low Back Pain; Pain; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Back Pain; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Charles Nwaokobia

  Evon Medics LLC

  PRINCIPAL INVESTIGATOR

• Evaristus Nwulia, MD, MHS

  Evon Medics LLC

  PRINCIPAL INVESTIGATOR

• Tanya Alim, MD

  Howard University

  PRINCIPAL INVESTIGATOR

• Haddi Ogunsola, MD

  Global Pain Management, LLC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Evaristus Nwulia, M.D., MHS

CONTACT

410-227-2005; enwulia@evonmedics.org

Maria Hipolito, MD

CONTACT

571-241-2766; mhipolito@howard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2024
• First Posted: November 4, 2024
• Study Start: October 23, 2024
• Primary Completion: November 30, 2025
• Study Completion: January 30, 2026
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)