Open-Label Placebo for Spinal Cord Injury Opioid Management

Overseen By Leon Morales-Quezada, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Spaulding Rehabilitation Hospital

Must be taking: Narcotics

Disqualifiers: Alcohol, Drug dependence, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 days

66 Participants Needed

Trial Summary

What is the purpose of this trial?

The use of the conditioning open-label placebo (COLP) paradigm will be studied as a dose extension method to lower opioid dosage in patients with spinal cord injury, polytrauma, and burn injury. The goal is to provide the same level of pain relief with a reduced opioid intake to diminish side effects as well as the risk of addiction associated with opioid treatment.

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 does require that your narcotic use is no more than 120 mg of morphine equivalent. You may need to adjust your opioid dosage as part of the study.

Is open-label placebo safe for humans?

There is no specific safety data available for open-label placebo treatments in the provided research articles. ^{1 2 3 4 5}

How does the open-label placebo treatment differ from other treatments for spinal cord injury opioid management?

The open-label placebo treatment is unique because it involves giving patients a placebo (a treatment with no active drug) while being transparent about its nature, aiming to harness the placebo effect to reduce opioid use and its side effects. This approach is different from traditional treatments that rely on active medications like opioids, which can have significant side effects and complications. ^{1 4 6 7 8}

Eligibility Criteria

This trial is for adults with moderate to severe pain from spinal cord injury, burns, or multiple traumas who are in the Spaulding Comprehensive Rehabilitation Unit. They must be stable, using opioids for pain but not more than a specified dose, and cannot have drug dependence history or certain medical conditions like uncontrolled cancer.

Inclusion Criteria

I have moderate to severe pain from nerve damage or injury.

I am 18 or older with a spinal cord injury or severe burn from Spaulding Rehabilitation.

With current narcotic use for pain control

Exclusion Criteria

History of alcohol or drug dependence, as self-reported

Current use of a ventilator

Pregnancy or breastfeeding. Participants with pregnancy capability will be tested for pregnancy by serum human chorionic gonadotropin (hCG) test

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either the Conditioning Open-Label Placebo (COLP) or standard opioid treatment for 6 days

6 days

Daily visits (in-person)

Voluntary COLP Continuation

Participants in the COLP group may continue the intervention during hospitalization if they agree

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

3-6 weeks

Treatment Details

Interventions

• Placebo

Trial Overview The study tests if a placebo given openly (patients know they're receiving it) can help reduce opioid doses while managing pain effectively in patients with serious injuries. The aim is to lessen opioid side effects and addiction risk without compromising on pain relief.

Participant Groups

Group I: Conditioning Open-Label Placebo Experimental Treatment 1 Intervention

Days 1 to 3 will include the acquisition phase where the opioid medication will be prescribed on a schedule of 3-4 times per day and paired with an open-label placebo. Day 4 and 6 will be the evoked phase, and patients will receive only the open-label placebo pill. On day 5 the opioid medication will be re-introduced as pharmacological reinforcement.

Group II: Treatment as usual Active Control 1 Intervention

Patients in the standard of care group will receive their analgesic treatment through Spaulding Pharmacy as prescribed by their treating physicians. The treatment regime will include an opioid medication at the standard recommended dosage. Participants in this group will receive the treatment orally for 6 consecutive days.

Who Is Running the Clinical Trial?

Spaulding Rehabilitation Hospital

Lead Sponsor

Trials

143

Recruited

11,200+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

Administering small doses of opioids directly into the spinal canal (intrathecal administration) can lead to the development of neuropathic pain and allodynia in individuals with spinal cord injuries.

This finding highlights the potential risks associated with opioid use in this specific patient population, suggesting that careful consideration is needed when prescribing opioids for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allodynia after acute intrathecal morphine administration in a patient with neuropathic pain after spinal cord injury. Parisod, E., Siddall, PJ., Viney, M., et al.[2019]

In a survey of 279 individuals with spinal cord injury pain (CSCIP), 63.8% were undergoing treatment, yet they reported high pain levels (average score of 52.8 out of 100), indicating that current treatments may not be sufficiently effective.

Among various treatments, acupuncture/magnetising, cannabis/alcohol, and physiotherapy/exercise were perceived as the most effective, while TENS/ultrasound and antidepressants were viewed as less effective, highlighting the need for further research into effective pain management strategies for CSCIP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic spinal cord injury pain: pharmacological and non-pharmacological treatments and treatment effectiveness. Heutink, M., Post, MW., Wollaars, MM., et al.[2015]

Pregabalin was found to be effective for managing neuropathic pain in chronic spinal cord injury patients, with strong evidence from multiple studies, while cannabinoids were deemed ineffective for the same condition.

Adverse events (AEs) such as dizziness and somnolence were common, leading to withdrawal rates that varied significantly across different medication types, highlighting the need for better reporting of AEs in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy, Adverse Events, and Withdrawal Rates of the Pharmacological Management of Chronic Spinal Cord Injury Pain: A Systematic Review and Meta-Analysis. Canavan, C., Inoue, T., McMahon, S., et al.[2022]

Intravenous morphine administration in the early phase of spinal cord injury (SCI) not only undermines locomotor recovery but also increases lesion size in a rodent model, indicating potential harm from its use.

The study found that morphine treatment led to a significant loss of neuron markers and altered glial cell responses, which were associated with decreased locomotor function and increased pain sensitivity, suggesting that morphine may be contraindicated for acute SCI management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurobiological Effects of Morphine after Spinal Cord Injury. Hook, MA., Woller, SA., Bancroft, E., et al.[2019]

Approximately one-third of individuals with spinal cord injury (SCI) experience persistent neuropathic pain, which is challenging to treat and significantly impacts quality of life.

Opioid treatment, while effective for pain relief, may hinder recovery of locomotor function and exacerbate pain development after SCI, suggesting a need for cautious use and the establishment of guidelines for opioid administration in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid administration following spinal cord injury: implications for pain and locomotor recovery. Woller, SA., Hook, MA.[2021]

This ongoing randomized controlled trial involves 70 patients recovering from dorsal lumbar interbody fusion surgery, investigating the effectiveness of adding open-label placebos to standard opioid treatment to reduce opioid consumption and side effects.

The study aims to provide insights into how open-label placebos can enhance pain management without compromising efficacy, potentially offering a cost-effective strategy to minimize opioid use in acute postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial. Sezer, D., de Leeuw, M., Netzer, C., et al.[2021]

In a rodent model of spinal cord injury, three consecutive days of intravenous morphine administration significantly increased the number of activated microglia and macrophages at the injury site, indicating a heightened immune response.

Repeated morphine treatment altered the function of these immune cells by increasing the production of neuropeptides linked to neurotoxicity, suggesting that morphine may negatively impact recovery after spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphine-induced changes in the function of microglia and macrophages after acute spinal cord injury. Terminel, MN., Bassil, C., Rau, J., et al.[2022]

In a meta-analysis of 276 patients with spinal cord injury, it was found that male patients and those with higher baseline pain levels experienced larger placebo responses in clinical trials for neuropathic pain.

The study concluded that these placebo responses are influenced by individual factors like sex and initial pain intensity, rather than the characteristics of the injury itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo response in neuropathic pain after spinal cord injury: a meta-analysis of individual participant data. Jutzeler, CR., Warner, FM., Cragg, JJ., et al.[2022]

References

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

Allodynia after acute intrathecal morphine administration in a patient with neuropathic pain after spinal cord injury. [2019]

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

Chronic spinal cord injury pain: pharmacological and non-pharmacological treatments and treatment effectiveness. [2015]

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

The Efficacy, Adverse Events, and Withdrawal Rates of the Pharmacological Management of Chronic Spinal Cord Injury Pain: A Systematic Review and Meta-Analysis. [2022]

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

Neurobiological Effects of Morphine after Spinal Cord Injury. [2019]

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

Opioid administration following spinal cord injury: implications for pain and locomotor recovery. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Morphine-induced changes in the function of microglia and macrophages after acute spinal cord injury. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Placebo response in neuropathic pain after spinal cord injury: a meta-analysis of individual participant data. [2022]