Clinical trial NCT06218407: Development and Evaluation of Computerized Chemosensory Based Orbitofrontal Networks Training for Treatment of Pain
Official title: Development and Evaluation of Computerized Chemosensory Based Orbitofrontal Networks Training for Treatment of Pain (CBOT-P)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Pain
Low Back Pain
Keywords: Chronic Pain (CP)
Pain
Negative Affect (NA)
Cognitive Impairments
Attenuation of Structural Brain loss in CP with high NA
PACS outcome
Orbitofrontal cortex
Chemosensory-Based Orbitofrontal Networks Training
Lead sponsor: Evon Medics LLC
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Howard University
name: Georgetown University
First posted: 2024-01-23
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The overarching goal of this study phase, Phase I component is to configure Computerized Chemosensory-Based Orbitofrontal Networks Training (CBOT) into Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain CBOT-Pain (or CBOT-P) for rapid and sustained reduction of Pain, Negative Affect (NA) and Cognitive Impairments. The investigators aimed at first establishing if stimulation parameters targeting key olfactory regions, and their associated networks, paired with tasks that synergistically activate the orbitofrontal cortex (OFC) would have significantly different acute (\< 7 days) effects in pain and NA intensity reductions. The hypothesis is that the short burst paradigm will more effectively activate the medial OFC and its functional connectivity with medial temporal affective networks, and result in greater reduction of affect and pain severity ratings after 7 days. The investigators will further examine if enhancing the odor regimen with beta-caryophyllene (BCP) content would have more dramatic effects in acute relief of pain, NA, and cognition.

Aim 1.1: To optimize CBOT-P stimulation parameters and olfactory stimulants for pain, affect and cognition in CP with and without high NA. This is a 14-day prospective study, in which fMRI and rs-fMRI will be acquired at baseline and day 7 during exposure to short vs long-burst CBOT stimulations. This is followed by daily treatment with short-burst versus long-burst CBOT paradigm over 14 days, during which pain and NA measures will be recorded daily by the subjects, and assessed by train research staff at baseline, day 7 and day 14.

Aim 1.2: To determine if CBOT regimen optimized with BCP content produces stronger and faster pain and affective response. This is a 14-day prospective study design, in which daily treatment of CBOT-PLUS (i.e., CBOT with BCP) will be compared against daily treatment with CBOT without BCP enhancement (CBOT). Subjects and clinicians are blinded to the assigned arms. Pain and NA measures will be recorded daily by the subjects and assessed by trained research staff at baseline and day 14.

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 homebased 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 for treatment of pain and negative affect. In a stakeholder value canvassing exercise 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 I of this Fast-Track SBIR application, the investigators will (a) configure CBOT-P regimen and stimulation parameters for faster onset of mood elevating and analgesic effects, focusing on Chronic Low Back Pain populations and (b) establish its neural mechanism of action through target-engagement studies of OFC activity and functional connectivity with other pain regulating regions at baseline.

Eligibility criteria: Inclusion Criteria:

1. Ages 18-85.
2. Pain duration \> 6 months.
3. Must meet the minimum criteria for cognitive function using the PROMIS 2-item cognitive screener \>3.
4. 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 surveys 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, Structured Clinical Interview for Psychiatric Disorders (SCID-5) and Columbia Suicide Severity Rating Scale (C-SSRS) and -
11. Participants must sign IRB-approved consent.

Exclusion Criteria:

1. Back surgery within the past six months.
2. Active worker's compensation or litigation claims.
3. New pain and/or psychiatric treatments within 2 weeks of enrollment.
4. Intent to add new or increase pain treatments during the study period, such as back surgery, nerve block procedures, or medications.
5. Intent to add new psychiatric treatments during the first 3 months of the study.
6. Any clinically unstable systemic illness that is judged to interfere with the trial.
7. 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.
8. Non-ambulatory status.
9. 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).

Primary outcomes:
measure: Relative changes in blood oxygen level dependent (BOLD) signals from fMRI of orbitofrontal brain regions in response to short durations (i.e., short-bursts) and to long durations (i.e., long-bursts) of repetitive odor stimulations. Aim 1.1
timeFrame: Baseline
measure: Changes in the resting-state functional connectivity between midbrain and corticolimbic brain regions Aim 1.1
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity Aim 1.1
timeFrame: Baseline to day 7
measure: Positive and Negative Affect Schedule (PANAS) rating scale Aim 1.1
timeFrame: Baseline to day 7
measure: Relative changes in blood oxygen level dependent (BOLD) signals from fMRI of orbitofrontal brain regions in response to short durations (i.e., short-bursts) and to long durations (i.e., long-bursts) of repetitive odor stimulations. Aim 1.1
timeFrame: 7 days after baseline
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity Aim 1.2
timeFrame: Baseline to day 7
measure: Positive and Negative Affect Schedule (PANAS) rating scale Aim 1.2
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity Aim 1.1
timeFrame: Baseline to day 14
measure: Positive and Negative Affect Schedule (PANAS) rating scale Aim 1.1
timeFrame: Baseline to day 14
measure: Changes in the resting-state functional connectivity between midbrain and corticolimbic brain regions Aim 1.1
timeFrame: Baseline to 14
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Numeric Rating Scale v1.0 - Pain Intensity Aim 1.2
timeFrame: Baseline to day 14
measure: Positive and Negative Affect Schedule (PANAS) rating scale Aim 1.2
timeFrame: Baseline to day 14
Secondary outcomes:
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.1 - Pain Interference scores. Aim 1.1
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Anxiety scores Aim 1.1
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Sleep Disturbance scores Aim 1.1
timeFrame: Baseline to day 7
measure: Pittsburgh Sleep Quality Index (PSQI) Aim 1.1
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Anxiety scores Aim 1.2
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Sleep Disturbance scores Aim 1.2
timeFrame: Baseline to day 7
measure: Pittsburgh Sleep Quality Index (PSQI) Aim 1.2
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v2.0 - Physical Function Aim 1.2
timeFrame: Baseline to day 7
measure: Patient Global Impression of Change Aim 1.2
timeFrame: Baseline to day 7
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.1 - Pain Interference scores. Aim 1.1
timeFrame: Baseline to day 14
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Anxiety scores Aim 1.1
timeFrame: Baseline to day 14
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Sleep Disturbance scores Aim 1.1
timeFrame: Baseline to day 14
measure: Pittsburgh Sleep Quality Index (PSQI) Aim 1.1
timeFrame: Baseline to day 14
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Anxiety scores Aim 1.2
timeFrame: Baseline to day 14
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Sleep Disturbance scores Aim 1.2
timeFrame: Baseline to day 14
measure: Pittsburgh Sleep Quality Index (PSQI) Aim 1.2
timeFrame: Baseline to day 14
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v2.0 - Physical Function Aim 1.2
timeFrame: baseline to day 14
measure: Patient Global Impression of Change Aim 1.2
timeFrame: Baseline to day 14
Other outcomes:
Locations:
city: Washington
country: United States
facility: Howard University
state: District of Columbia
Study officials:
affiliation: Evon Medics LLC
name: Charles Nwaokobia
role: PRINCIPAL_INVESTIGATOR
affiliation: Howard University
name: Evaristus Nwulia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Howar
name: Tanya Alim, MD
role: PRINCIPAL_INVESTIGATOR
References: