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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if prescription opioids for chronic pain affect the brain's structure using MRI scans. Researchers seek to understand how opioids might alter the white matter, which facilitates communication between different brain regions. Participants will join one of two groups: one receiving opioids and the other a placebo, both with a personalized pain management plan. This trial targets individuals aged 65 or older who have experienced moderate to severe daily pain for over three months and have not found relief with other pain medications. 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 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that long-term use of prescription opioids can be risky. Studies have found a higher chance of serious problems, such as overdose, addiction, and broken bones. The FDA has updated guidelines for prescribing opioids to emphasize caution with long-term use. However, opioids often manage ongoing pain and are usually safe when prescribed and taken correctly for short periods. Discussing any concerns with a doctor is important, as they can help balance the benefits and risks based on individual health needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic pain?

Researchers are excited about the treatment approach for chronic pain in this trial because it integrates a comprehensive tiered pain management plan alongside prescription opioids or their placebos. Unlike standard options, which often rely heavily on just medication, this method combines multiple non-drug therapies like acupuncture, massage, and physical therapy, with cognitive behavioral therapy and advanced interventions like nerve stimulators. This holistic approach aims to address pain from multiple angles, potentially offering more sustainable relief and minimizing opioid reliance, which is a significant concern with traditional treatments.

What evidence suggests that this trial's treatments could be effective for chronic pain?

This trial will compare the effects of prescription opioids with a placebo for chronic pain management. Studies have shown that the effectiveness of long-term opioid use for chronic pain remains unclear. Evidence does not strongly support that opioids provide lasting pain relief or improve daily activities. Some research even suggests that higher doses of opioids might worsen pain. Due to these findings, other treatments, such as non-opioid medications, are increasingly used. While opioids can be part of a pain management plan, their long-term benefits remain debated. ^{1 2 4 6 7}

Who Is on the Research Team?

Nafisseh Warner

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK556253/

Opioid Treatments for Chronic Pain - NCBI Bookshelf - NIH Trials of patients with prescription opioid dependence found buprenorphine maintenance associated with better outcomes than buprenorphine taper and similar ...

2. acpjournals.org acpjournals.org/doi/10.7326/M14-2559

The Effectiveness and Risks of Long-Term Opioid Therapy ... Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function.

3. cdc.gov cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

CDC Clinical Practice Guideline for Prescribing Opioids ... The systematic review addressed the effectiveness of long-term opioid therapy for outcomes related to pain, function, and quality of life ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2793224

Patterns in Nonopioid Pain Medication Prescribing After ... Results of this study showed increases in nonopioid pain medication prescribing after the release of the 2016 CDC guideline.

5. sciencedirect.com sciencedirect.com/science/article/pii/S152659001630356X

Higher Prescription Opioid Dose is Associated With Worse ... Higher opioid dose was associated with poorer pain outcomes and more health care utilization. •. Differences were detected among groups in rates of self- ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK458655/

Pain Management and the Opioid Epidemic - NCBI Bookshelf A study of 1,477 adults prescribed opioids for chronic pain, for example, showed that patients who used lower or intermittent doses of opioids had pain outcomes ...

7. fda.gov fda.gov/safety/medical-product-safety-information/fda-requiring-opioid-pain-medicine-manufacturers-update-prescribing-information-regarding-long-term

FDA is Requiring Opioid Pain Medicine Manufacturers to ... FDA is Requiring Opioid Pain Medicine Manufacturers to Update Prescribing Information Regarding Long-Term Use: Drug Safety Communication.