Prescription Opioids for Chronic Pain

(I-COAP Trial)

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Opioids

Disqualifiers: Severe mental disorders, Liver disease, Kidney disease, Cognitive impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 6 weeks

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have used opioids in the past 6 months, you would not be eligible to participate.

What data supports the effectiveness of the drug Opioid for chronic pain?

Research shows that opioids can reduce pain intensity by at least 30% in the short term for conditions like neuropathic and musculoskeletal pain. However, many patients experience side effects, and only a few continue long-term use due to concerns about tolerance and addiction. ^{1 2 3 4 5}

What safety data exists for the use of prescription opioids in chronic pain management?

Opioids for chronic pain can cause side effects like dry mouth, nausea, and constipation, and about 22% of patients stop using them due to these issues. Long-term use may lead to more serious problems like addiction, hormonal changes, and immune system suppression. There is also a small risk of death with high doses. ^{6 7 8 9 10}

How does the opioid drug for chronic pain differ from other treatments?

This treatment is unique because it involves using placebos alongside opioids, which can mimic medication effects through learning mechanisms, potentially extending the benefits of opioids without increasing dosage. This approach is different from standard opioid treatments that do not typically incorporate placebos to enhance or extend pain relief. ^{4 5 11 12 13}

What is the purpose of this trial?

The purpose of this study is to determine whether exposure to prescription opioids is associated with brain structural changes on magnetic resonance imaging (MRI), with the primary outcome of white matter integrity as measured by fractional anisotropy of the corpus callosum.

Research Team

Nafisseh Warner

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for older adults who have been experiencing chronic pain. Participants must be eligible to undergo MRI scans, which will be used to observe potential changes in brain structure due to opioid use.

Inclusion Criteria

I am 65 years old or older.

I have had moderate to severe knee or shoulder pain almost daily for 3 months.

Exclusion Criteria

I do not have severe liver or kidney disease.

Life expectancy < 12 months

Non-English speaking

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an individualized multimodal pain treatment pathway for 6 weeks, including either prescription opioids or placebo

6 weeks

Baseline visit, 6-week visit

Taper

Participants undergo opioid/placebo taper

2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 6 months and 1 year

12 months

6-month phone call, 1-year visit

Treatment Details

Interventions

• Opioid
• Opioid Placebo

Trial Overview The study aims to find out if prescription opioids can cause changes in the brain's white matter integrity, specifically in the corpus callosum area. This is measured using MRIs. Some participants will receive opioids and others a placebo without active medication.

Participant Groups

Group I: Opioid Group Experimental Treatment 1 Intervention

The participant will be plugged into an individualized comprehensive tiered pain plan that can include: Tier one (Acetaminophen, NSAIDS, Topicals, TENS unit, Massage, Acupuncture, Physical therapy. Tier two (Cognitive behavioral therapy, joint injections, nerve ablations, peripheral nerve stimulators) and less commonly Tier three (duloxetine, gabapentin). This is modeled after clinical practice. The participants will additionally receive prescription opioids for 6 weeks.

Group II: Placebo Group Placebo Group 1 Intervention

The participant will be plugged into an individualized comprehensive tiered pain plan that can include: Tier one (Acetaminophen, NSAIDS, Topicals, TENS unit, Massage, Acupuncture, Physical therapy. Tier two (Cognitive behavioral therapy, joint injections, nerve ablations, peripheral nerve stimulators) and less commonly Tier three (duloxetine, gabapentin). This is modeled after clinical practice. The participants will additionally receive a prescription opioid placebo for 6 weeks.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

A systematic review of 234 randomized placebo trials involving 10,525 patients found that placebo interventions generally do not have clinically important effects across various health conditions, with a pooled effect size indicating minimal benefit.

However, placebo interventions showed some influence on patient-reported outcomes, particularly for pain and nausea, although the effects varied widely and were often difficult to separate from reporting biases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo interventions for all clinical conditions. Hróbjartsson, A., Gøtzsche, PC.[2022]

A systematic review of 34 trials involving 5,546 patients found that oral opioids used for non-cancer pain resulted in higher rates of adverse events compared to placebo, with common issues including dry mouth (25%), nausea (21%), and constipation (15%).

Approximately 22% of patients discontinued opioid treatment due to adverse events, highlighting the potential safety concerns associated with opioid use in non-cancer pain management, especially since most trials lasted less than four weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. Moore, RA., McQuay, HJ.[2022]

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]

Placebo treatments can be effective in managing chronic pain, and their efficacy is influenced by factors such as the patient-physician relationship rather than just the method of administration (e.g., double blind or open label).

Emerging models like 'predictive coding' and 'bayesian brain' suggest that the brain's expectations and learned experiences play a crucial role in how placebos work, indicating that both chronic pain and its relief through placebos are largely influenced by non-conscious processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. Kaptchuk, TJ., Hemond, CC., Miller, FG.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Seeing others is believing-analgesic placebo effects through observational learning?] [2022]

2. England pubmed.ncbi.nlm.nih.gov

Placebo interventions for all clinical conditions. [2022]

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

Long-term, high-dose opioid prescription for chronic non-cancer pain in primary care: an observational study. [2023]

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

Opioids in chronic non-cancer pain: systematic review of efficacy and safety. [2022]

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

Relieving acute pain (RAP) study: a proof-of-concept protocol for a randomised, double-blind, placebo-controlled trial. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. [2022]

7. 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]

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

Effectiveness of long-term opioid therapy for chronic non-cancer pain. [2011]

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

Prevalence of side effects of prolonged low or moderate dose opioid therapy with concomitant benzodiazepine and/or antidepressant therapy in chronic non-cancer pain. [2009]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Chronic pain-related changes in endogenous opioid analgesia: a case report. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

The Self-administration of Analgesic Drugs in Experimentally Induced Chronic Pain. [2019]