Computerized Brain Training for Lower Back Pain

(CBOT-P-2 Trial)

Recruiting at 2 trial locations

Overseen By Evaristus Nwulia, M.D., MHS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Evon Medics LLC

Must be taking: Opioids

Disqualifiers: Back surgery, Litigation, Pregnancy, 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: 1

Duration: 6 months

220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new brain training method, Computerized Chemosensory-Based Orbitofrontal Cortex Training for Pain (CBOT), to assist individuals with chronic low back pain. The goal is to determine if this computerized training, combined with a natural supplement, can reduce pain and improve mood, cognition, and brain health. The trial compares the new treatment with a placebo to assess any real benefits. Suitable participants have experienced low back pain for over six months and currently use opioids, but they must not increase their dosage during the study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking opioids, you must have been on them for at least three months and cannot increase the dosage during the study.

What prior data suggests that this computerized brain training is safe for treating chronic low back pain?

Research has shown that the Computerized Chemosensory-Based Orbitofrontal Cortex Training for Pain (CBOT-P) is under study for its potential to alleviate chronic low back pain. This treatment combines brain training with beta caryophyllene (BCP), a compound that might help relieve pain.

Currently, detailed safety information about CBOT-P with BCP is not available. However, its status in a Phase 2 trial indicates prior testing in humans. Phase 2 trials typically assess the treatment's effectiveness and examine its safety more closely, suggesting early evidence of sufficient safety for broader testing.

While specific safety details for CBOT-P with BCP remain unclear, reaching this trial phase implies a reasonable level of safety so far. Those interested in the trial should be aware that the treatment is still under investigation, and more detailed safety information may emerge as the trial progresses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for lower back pain?

Researchers are excited about the Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) because it offers a unique approach to managing lower back pain. Unlike traditional treatments like pain medications and physical therapy, CBOT targets the brain's orbitofrontal cortex using a computerized method that involves chemosensory inputs. This innovative approach aims to retrain the brain's response to pain without the need for drugs. Additionally, the experimental arm of the trial combines CBOT with beta caryophyllene (BCP), a compound found in essential oils, which could enhance pain relief through a natural, non-invasive method. These features make CBOT stand out as a potentially groundbreaking treatment for those suffering from chronic lower back pain.

What evidence suggests that this computerized brain training is effective for chronic low back pain?

Research has shown that a new method called Computerized Chemosensory-Based Orbitofrontal Cortex Training with beta caryophyllene (CBOT-P), which participants in this trial may receive, might help reduce chronic low back pain. This method targets a part of the brain involved in processing pain. Studies have found that CBOT-P not only aims to lessen pain but also to boost mood and improve cognitive skills. Early results suggest this training might prevent certain brain changes linked to long-term pain, such as shrinkage in specific brain areas. This approach is based on the idea that altering brain activity can lead to better pain control and improved mental health for those with chronic pain. While more research is needed to confirm these benefits, the initial findings are promising. ^{1 3 4 5 6}

Who Is on the Research Team?

Evaristus Nwulia, MD, MHS

Principal Investigator

Evon Medics LLC

Tanya Alim, MD

Principal Investigator

Howard University

Haddi Ogunsola, MD

Principal Investigator

Global Pain Management, LLC

Charles Nwaokobia

Principal Investigator

Evon Medics LLC

Are You a Good Fit for This Trial?

This trial is for individuals with chronic low back pain who are interested in a non-drug treatment. Participants should be willing to undergo brain scans and complete various assessments. Specific details about age, health conditions, or other criteria aren't provided here.

Inclusion Criteria

My back pain is chronic but not due to a major spine issue.

My average pain level is above 5/10, mainly in my lower back.

Must meet the minimum criteria for cognitive function using the PROMIS 4-item cognitive screener >3

Exclusion Criteria

I cannot walk by myself.

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

I have not had back surgery in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily treatment with CBOT-P device or Sham device for chronic low back pain

6 months

Baseline, months 1, 3, and 6 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT)
• Computerized Chemosensory-Based Orbitofrontal Cortex Training for Pain

Trial Overview The study tests a computerized training called CBOT-P designed to reduce pain by targeting the brain's orbitofrontal cortex. It will be compared to a sham (fake) version of the training to see if it truly works over time.

How Is the Trial Designed?

Group I: CBOT-P [CBOT + beta caryophyllene (BCP)] Experimental Treatment 1 Intervention

CBOT device with BCP

Group II: Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) Placebo Group 1 Intervention

CBOT device

Who Is Running the Clinical Trial?

Evon Medics LLC

Lead Sponsor

Trials

5

Recruited

1,000+

Georgetown University

Collaborator

Trials

355

Recruited

142,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Family and Medical Counseling Service, Inc

Collaborator

Trials

3

Recruited

610+

Global Pain Management, LLC

Collaborator

Trials

1

Recruited

220+

Howard University

Collaborator

Trials

44

Recruited

15,200+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Published Research Related to This Trial

Chronic low back pain (cLBP) is primarily maintained by neuroplastic changes in the brain rather than just peripheral factors, as shown by a meta-analysis of 17 fMRI studies involving 553 patients.

The study identified significant brain activation clusters associated with cLBP, indicating potential imbalances in GABAergic modulation and dysfunction in pain modulation systems, which contribute to persistent pain experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dysfunctional Descending Pain Modulation System in Chronic Nonspecific Low Back Pain: A Systematic Review and ALE Meta-Analysis. Hazra, S., Handa, G., Nayak, P., et al.[2022]

The brain processes pain and reward through overlapping systems, with the orbitofrontal cortex and opioids linked to the pleasurable ('liking') aspects of reward, while the ventral striatum and dopamine are associated with the motivational ('wanting') aspects.

Pain relief is highlighted as a significant rewarding stimulus that can influence pain sensitivity and operant learning, suggesting that understanding these interactions could lead to better insights into chronic pain mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral interactions of pain and reward and their relevance for chronic pain. Becker, S., Gandhi, W., Schweinhardt, P.[2014]

Different brain regions are responsible for processing various aspects of pain, such as pain detection, intensity, and unpleasantness, as shown by a regression analysis of brain activity in response to noxious heat.

The anterior cingulate cortex, frontal inferior cortex, and thalamus are linked to the pain threshold, while the periventricular gray and posterior cingulate cortex are associated with pain intensity, and the posterior anterior cingulate cortex relates to the unpleasantness of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis. Tölle, TR., Kaufmann, T., Siessmeier, T., et al.[2019]

A novel virtual reality neuroscience-based therapy (VRNT) significantly reduced pain intensity and interference in 31 participants with chronic back pain compared to usual care, with effects lasting for at least two weeks after treatment.

VRNT not only improved pain-related outcomes but also enhanced overall functioning by potentially altering brain networks associated with pain, as indicated by MRI findings showing changes in connectivity and white matter integrity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Virtual Reality Neuroscience-based Therapy on Clinical and Neuroimaging Outcomes in Patients with Chronic Back Pain: A Randomized Clinical Trial. Čeko, M., Baeuerle, T., Webster, L., et al.[2023]

A study of 49 subacute back pain patients used advanced brain imaging techniques to identify functional connections in the brain that can predict changes in pain intensity over a year, highlighting the importance of networks involved in pain modulation and integration.

The model developed showed strong predictive power, with correlations between actual and predicted pain scores ranging from r = 0.33 to 0.72, and high accuracy in classifying patients based on their pain outcomes, outperforming previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A neuroimaging marker for predicting longitudinal changes in pain intensity of subacute back pain based on large-scale brain network interactions. Park, BY., Lee, JJ., Kim, HJ., et al.[2021]

The placebo effect can lead to pain relief by decreasing activity in specific brain regions associated with pain modulation, such as the rostral anterior cingulate cortex and the insula, as shown through neuroimaging studies.

The analgesic effects of placebo are linked to the activation of the endogenous opioid system and dopamine release in the nucleus accumbens, suggesting that both opioid and dopamine pathways play crucial roles in how expectations can influence pain perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging study of placebo analgesia in humans. Qiu, YH., Wu, XY., Xu, H., et al.[2021]

Patients with chronic low back pain (cLBP) showed reduced connectivity in the brain's reward pathways compared to pain-free controls, indicating a potential neural basis for the persistence of pain.

Increased pain intensity in cLBP patients was associated with enhanced connectivity in these pathways, suggesting that the brain's reward system may play a role in managing pain and could be targeted for neuromodulation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired mesocorticolimbic connectivity underlies increased pain sensitivity in chronic low back pain. Yu, S., Li, W., Shen, W., et al.[2021]

Chronic back pain patients exhibit reduced habitual behavior and increased hippocampal responses compared to healthy controls, indicating a potential bias in learning and motivation due to pain.

The study found that the duration of pain symptoms, along with levels of depression and anxiety, significantly influenced brain activity and behavior, suggesting that these clinical characteristics play a crucial role in maladaptive learning processes in chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain-behaviour correlates of habitual motivation in chronic back pain. Nees, F., Ruttorf, M., Fuchs, X., et al.[2022]

Using fMRI, the study found that pleasant touch (like velvet) activates the orbitofrontal cortex more than neutral touch (like wood), highlighting the brain's specific response to pleasurable sensations.

The research suggests that the orbitofrontal cortex processes different types of rewarding stimuli, including touch, taste, and smell, which helps us understand the neural basis of emotions related to pleasure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas. Francis, S., Rolls, ET., Bowtell, R., et al.[2019]

In a study of 39 knee osteoarthritis patients, both duloxetine (DLX) and placebo provided similar levels of pain relief over a 3-month treatment period, indicating that subjective pain relief can occur regardless of the treatment type.

Distinct brain mechanisms were identified for pain relief: changes in gray matter density and functional connectivity were linked to analgesia in both groups, suggesting that pharmacological treatments like DLX can be differentiated from placebo based on objective brain biomarkers, which is important for developing personalized pain therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inferring distinct mechanisms in the absence of subjective differences: Placebo and centrally acting analgesic underlie unique brain adaptations. Tétreault, P., Baliki, MN., Baria, AT., et al.[2020]

This study reveals that conditioned pain modulation (CPM) leads to increased activity in the orbitofrontal cortex (OFC) and amygdala, which correlates with reduced subjective pain ratings in healthy young males.

The findings suggest that the pain inhibition process through CPM is primarily controlled by the OFC and amygdala, occurring before any decrease in activity in sensory areas of the brain, indicating a complex interplay between pain perception and modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study. Moont, R., Crispel, Y., Lev, R., et al.[2021]

The study implanted electrodes in four pain-related brain areas of rats and found that noxious laser stimulation led to significant changes in brain oscillations, specifically a decrease in α and β band power and an increase in γ band power.

Using generalized linear models, researchers achieved an 86% accuracy in distinguishing between noxious and innoxious stimuli based on local field potential features, highlighting the potential for understanding how different brain regions collaborate in pain perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracting Neural Oscillation Signatures of Laser-Induced Nociception in Pain-Related Regions in Rats. Li, X., Zhao, Z., Ma, J., et al.[2018]

Functional brain imaging techniques have significantly advanced our understanding of how the brain processes pain, revealing a 'pain matrix' that includes various brain regions activated during pain perception.

Dysfunctional interactions between the brain's ascending and descending pain systems may play a crucial role in the development and persistence of chronic pain, highlighting potential targets for therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Functional imaging in pain research]. Somborski, K., Bingel, U.[2021]

In a study involving 15 healthy volunteers, researchers found that specific brain regions, including the rostral anterior cingulate cortex and dorsolateral prefrontal cortices, can decode the location of painful stimuli (arm or leg) during both anticipation and experience of pain.

This research highlights that the brain's descending pain modulatory system carries spatial information about pain, suggesting that our brain can specifically target pain relief based on where it is felt, which enhances our understanding of how pain is controlled in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Representation of spatial information in key areas of the descending pain modulatory system. Ritter, C., Hebart, MN., Wolbers, T., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06218407

Study Details | NCT06218407 | Development and ... The Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain (CBOT-P) is a project to develop an ...

2. trialx.com trialx.com/clinical-trials/listings/303023/development-and-evaluation-of-computerized-chemosensory-based-orbitofrontal-networks-training-for-treatment-of-pain-cbot-p/

Clinical Research Trial Listing ( Chronic Pain Aim 2.2 To determine if CBOT-P significantly prevents or reduces progressive shrinkage in the orbitofrontal cortex (OFC), cingulate cortex, and ...

3. withpower.com withpower.com/trial/phase-2-chronic-pain-9-2024-e63c9

Computerized Brain Training for Lower Back Pain (CBOT-P-2 Trial) Trial Overview The study tests a computerized training called CBOT-P designed to reduce pain by targeting the brain's orbitofrontal cortex. It will be compared ...

4. reporter.nih.gov reporter.nih.gov/project-details/9881969

Proof of concept study to treat negative affect in chronic low ... This proposal responds to RFA-NS-19-029 to address the need for better evidence-based pain treatment for patients with chronic low back pain (CLBP) who have ...

5. trial.medpath.com trial.medpath.com/clinical-trial/704e7272f67bbaba/nct06218407-development-evaluation-chemosensory-orbitofrontal-networks-training-treatment-pain

Development and Evaluation of Computerized Chemosensory ... The overarching goal of this study phase, Phase I component is to configure Computerized Chemosensory-Based Orbitofrontal Networks Training (CBOT...

6. ctv.veeva.com ctv.veeva.com/study/development-and-evaluation-of-computerized-chemosensory-based-orbitofrontal-networks-training-for-tr-1

Development and Evaluation of Computerized Chemosensory ... 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 ...