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

Official title

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

Overview

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.

Detailed description

The Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain (CBOT-P) is a project to develop an effective, scalable, user-friendly, and home-based neuromodulatory platform for broad-spectrum treatment of chronic pain conditions with associated negative affect and cognitive impairments.

The small business, Evon Medics created the olfactory pulsing technology called Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT-P) to enable home-based modulation of the OFC and subcortical limbic structures to treat pain and negative affect. In a stakeholder value canvassing exercise chronic pain (CP) sufferers and pain doctors unanimously desire new non-invasive, home-based, safe, and effective interventions that can reduce pain severity by more than 10%, suggesting that current treatments have limitations. Anterograde and retrograde anatomical tracings have been used to demonstrate direct (monosynaptic) anatomical connection between the OFC and the descending inhibitory pain nodes at the midbrain periaqueductal gray matter (PAG). Transition to CP is marked by weakened modulation of the PAG descending inhibition.

In this study phase, Phase II of this Fast-Track SBIR application, the investigators will conduct a multi-site study of 220 adult patients with CLBP to establish stronger evidence that the product controls pain, reduces negative mood, improves cognition, and protects the brain from shrinking in six months of treatment. Participants in this phase will be randomly assigned in a 1:1 ratio to daily treatment with CBOT-P device (i.e., CBOT with beta-caryophyllene (BCP) compared to a control (Sham) device that looks like the device but does not have the active ingredients and the programmed parameters on the ability to improve pain, mood, cognition and brain functions in chronic pain. Structural magnetic resonance imaging (MRI) will be acquired at baseline and after 6 months of daily treatment with optimized CBOT (based on Phase I) or Sham CBOT device to improve masking. Pain and NA measures, Cognitive batteries, and physical and functional measures will be assessed at baseline, months 1, 3, and 6. Participants would be encouraged through mobile health prompts to complete subjective pain, affect, sleep, and functional studies at the end of each study week. CLBP volunteers, radiologists, and clinicians assessing outcome measures will be blinded to these assignments.

The investigators will also collect user experiences to help refine a final marketable CBOT product, enter the FDA breakthrough designation program for pain that would lead to Medicare/Medicaid reimbursement, engage a wider network of pain stakeholders, and establish marketing for commercial success.

Interventions

• Combination product Computerized Chemosensory-Based Orbitofrontal Cortex Training for Pain
  CBOT device with beta-caryophyllene
• Combination product Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT)
  CBOT device administering continuous olfactoy stimuli with no BCP

Primary outcome measures

• Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity (Aim 2.1) [Time frame: Baseline to month 1 visit]
• Positive and Negative Affect Schedule (PANAS) rating scale (Aim 2.1) [Time frame: Baseline to month 1 visit]
• Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity (Aim 2.1) [Time frame: Baseline to month 3 visit]
• Positive and Negative Affect Schedule (PANAS) rating scale (Aim 2.1) [Time frame: Baseline to month 3 visit]
• Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity (Aim 2.1) [Time frame: Baseline to month 6 visit]
• Positive and Negative Affect Schedule (PANAS) rating scale (Aim 2.1) [Time frame: Baseline to month 6 visit]
• Grey Matter Volumes of OrbitoFrontal Cortex and Hippocampus Aim 2.2 [Time frame: Baseline and 6 months]

Secondary outcome measures (12)

• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.1 - Pain Interference scores. Aim 2.1 [Time frame: Baseline to month 1 visit]
• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Anxiety scores Aim 2.1 [Time frame: Baseline to month 1 visit]
• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Sleep Disturbance scores Aim 2.1 [Time frame: Baseline to month 1 visit]
• Total Sleep Time (TST) Centrepoint Insight Actigraph watch Sleep Parameters Aim 2.1 [Time frame: Baseline and 1 month]
• Sleep Onset Latency (SOL) Centrepoint Insight Actigraph watch Sleep Parameters Aim 2.1 [Time frame: Baseline and 1 month]
• Sleep Efficiency (SE) Centrepoint Insight Actigraph watch Sleep Parameters Aim 2.1 [Time frame: Baseline and 1 month]
• Wake After Sleep Onset (WASO) Centrepoint Insight Actigraph watch Sleep Parameters Aim 2.1 [Time frame: Baseline and 1 month]
• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v2.0 - Physical Function Aim 2.1 [Time frame: Baseline to month 1 visit]
• Patient Global Impression of Change Aim 2.1 [Time frame: Baseline to month 1 visit]
• California Verbal Learning Test (CVLT) Aim 2.1 [Time frame: Baseline to month 1 visit]
• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.1 - Pain Interference scores. Aim 2.1 [Time frame: Baseline to month 3 visit]
• Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Anxiety scores Aim 2.1 [Time frame: Baseline to month 3 visit]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• Howard University — Washington D.C.
• Global Pain Management LLC — Pasadena

Identifiers

NCT: NCT06671132 · CBOTP2NS125745 · 4R44NS125745-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗