Treatments for Chronic Back Pain and Opioid Use Disorder

Overseen By Meghan Ford

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must be taking: Short acting opioids

Must not be taking: Antidepressants, Long acting opioids

Disqualifiers: Diabetes, Hypertension, Neurological conditions, 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: 4

Duration: 3 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to track brain functional changes in individuals with i) chronic back pain + opioid use (CBP+O) and individuals with ii) chronic back pain + opioid misuse disorder (CBP+mOUD) following a brief drug delay and re-exposure manipulation. Re-exposure could be placebo, the participant's own opioid dose, or a dopaminergic treatment (DA+NSAID). The participants will be also evaluated for changes in cognition, emotion, and motor abilities with opioid delay and re-exposure to placebo, opioid, or DA+NSAID.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be on regular short-acting opioid therapy for at least 3 months before joining. You should discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the drugs used for chronic back pain and opioid use disorder?

Research indicates that opioids may provide short-term pain relief for chronic back pain, but their long-term effectiveness and safety are unclear, with potential risks including addiction and overdose. NSAIDs like naproxen are often used for pain relief, and studies suggest they may be as effective as opioids for chronic low back pain without the same level of risk. ^{1 2 3 4 5}

Is opioid treatment generally safe for chronic back pain?

Opioids can provide short-term pain relief for chronic back pain, but their long-term safety is uncertain. Common short-term side effects include constipation, nausea, and increased risk of falls, while long-term use may lead to addiction, overdose, depression, and sexual dysfunction. ^{1 5 6 7 8}

How do opioids differ from other drugs for chronic back pain and opioid use disorder?

Opioids are unique because they are often used for short-term relief of acute back pain, but their long-term use can lead to increased pain sensitivity and addiction. Unlike other treatments, opioids can cause hormonal issues and decreased quality of life, making them a challenging option for chronic back pain management. ^{1 3 9 10 11}

Research Team

Apkar Apkarian, PhD

Principal Investigator

Northwestern University Feinberg School of Medicine

Eligibility Criteria

This trial is for adults over 18 with chronic low back pain who have been on short-acting opioid therapy for at least 3 months. Participants must be in stable health, able to read and speak English, and willing to use a daily eDiary. Exclusions include diabetes, long-acting opioids or high doses of opioids (>50mg/day), uncontrolled hypertension, lactose intolerance, certain implants, unstable antidepressant use, other chronic pain/neurological conditions, significant medical diseases like heart failure or renal insufficiency.

Inclusion Criteria

Must be in generally stable health;

Male or female, age equal or greater than 18 years, with no racial/ethnic restrictions;

You must be able to read and understand instructions as well as questionnaires.

Exclusion Criteria

An established diagnosis of diabetes (type 1 or type 2)

Use of a patch or long acting opioid therapy (e.g. anticipated duration of action > 6 hours)

You have high blood pressure that is not well managed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 hours

1 visit (in-person)

Treatment

Participants undergo three imaging visits with different drug interventions, including opioids, carbidopa/levodopa, and placebo, with brain MRI scans and cognitive assessments.

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in pain and craving using the Pain and Craving Index (PCI) and other assessments.

3 weeks

Treatment Details

Interventions

• Carbidopa-Levodopa
• Naproxen
• Opioids

Trial Overview The study observes brain function changes in people with chronic back pain using opioids regularly (CBP+O) and those misusing them (CBP+mOUD). It involves a drug delay followed by re-exposure to either placebo; the participant's usual opioid dose; or dopaminergic treatment combined with NSAID. The impact on cognition, emotion, and motor skills will also be assessed.

Participant Groups

Group I: Chronic Back Pain with Opioid Use Experimental Treatment 3 Interventions

Subjects of this arms will be on a previously prescribed, short term acting opioid. Previous to each of the three imaging visits, subjects will be instructed to withhold from taking their regular morning opioid dose. Subjects will be randomized into a group that determines the sequence of which they will receive the study drugs. The three sequences are as follows: 1. treatment dose #1: 25mg carbidopa/ 100mg levodopa + 500mg naproxen, treatment dose #2: subjects prescribed, short acting opioid; 2. treatment dose #1: placebo, treatment dose #2: subjects prescribed, short acting opioid; or 3. treatment #1: subjects prescribed, short acting opioid, treatment dose #2: placebo.

Group II: Chronic Back Pain with Opioid Misuse Disorder Experimental Treatment 3 Interventions

Subjects of this arms will be on a previously prescribed, short term acting opioid. Previous to each of the three imaging visits, subjects will be instructed to withhold from taking their regular morning opioid dose. Subjects will be randomized into a group that determines the sequence of which they will receive the study drugs. The three sequences are as follows: 1. treatment dose #1: 25mg carbidopa/ 100mg levodopa + 500mg naproxen, treatment dose #2: subjects prescribed, short acting opioid; 2. treatment dose #1: placebo, treatment dose #2: subjects prescribed, short acting opioid; or 3. treatment #1: subjects prescribed, short acting opioid, treatment dose #2: placebo.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Shirley Ryan AbilityLab

Collaborator

Trials

212

Recruited

17,900+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

This systematic review analyzed 16 randomized trials and 8 observational studies involving 1427 and 1190 patients, respectively, to evaluate the efficacy and safety of long-acting opioids for chronic non-cancer pain.

The review found insufficient evidence to conclude that different long-acting opioids have distinct efficacy or safety profiles compared to each other or to short-acting opioids, although some evidence suggested that long-acting and short-acting oxycodone are equally effective for pain control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. Chou, R., Clark, E., Helfand, M.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Randomized clinical trial comparing buprenorphine/naloxone and methadone for the treatment of patients with failed back surgery syndrome and opioid addiction. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of Opioids and Nonsteroidal Anti-Inflammatory Drugs on Chronic Low Back Pain and Related Measures: Results from the PRECISION Pain Research Registry. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Opioids for low back pain. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

[Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration]. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Opioids and Chronic Pain: An Analytic Review of the Clinical Evidence. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Pharmacological management of chronic low back pain in older patients: a randomized controlled trial of the effect of pregabalin and opioid administration. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Comparison of Lumbar Fusion for Back Pain and Opioid Use at County and Managed Care Hospitals. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

[Noninvasive Treatments for Acute and Chronic Back Pain]. [2022]