Development and Evaluation of Computerized Chemosensory Based Orbitofrontal Networks Training for Treatment of Pain
Condition: Chronic Pain; Low Back Pain
MeSH terms: Low Back Pain; Chronic Pain
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) short burst paradigm; Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) long burst paradigm; Computerized Chemosensory-Based Orbitofrontal Cortex Training plus beta caryophyllene (CBOT-Plus); Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT)
Intervention type(s): Combination Product; Combination Product; Combination Product; Combination Product
Intervention description(s): The CBOT device is designed to stimulate intensive neural activity in the medial orbitofrontal regions over long periods of time.; The CBOT device is designed to stimulate intensive neural activity in the lateral orbitofrontal regions and networks over long periods of time.; CBOT device enhanced with BCP.; CBOT device administering continuous olfactory stimuli (i.e., not programmed for short or long burst), and without BCP enhancement.
Other intervention name(s): CBOT-Short; CBOT-Long; CBOT Plus; CBOT
Intervention MeSH terms: Caryophyllene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
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