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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to manage pain for individuals with spinal cord injuries, polytrauma, or burn injuries. The researchers aim to determine if a special type of placebo (a treatment with no active drug) can reduce the need for opioid painkillers while still providing effective pain relief. This approach could lower the risk of addiction and side effects from opioids. The trial seeks patients who currently use opioids for pain control and have experienced spinal cord injury or similar conditions for less than five years. Participants will either continue their regular pain treatment or try the new approach with the placebo. As an unphased trial, this study offers a unique opportunity to contribute to innovative pain management research that could benefit many in the future.

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.

What prior data suggests that this method is safe for reducing opioid dosage in spinal cord injury patients?

Research has shown that a conditioning open-label placebo (COLP) can reduce opioid use without compromising pain relief. This method holds promise for managing pain and reducing addiction risk. However, specific safety information for open-label placebo treatments is not available. Studies have not reported negative side effects or safety issues. Since open-label placebos involve openly administering a placebo, they are generally considered safe. The placebo lacks active medication, suggesting a low risk of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel approach to managing opioid use for spinal cord injury patients. Unlike standard care options that rely solely on opioid medications, this trial examines the potential of an open-label placebo to reduce opioid dependency. By introducing a placebo alongside opioids and then transitioning to the placebo alone, researchers hope to discover if this method can effectively manage pain while minimizing opioid use. This could lead to a significant reduction in opioid-related side effects and dependency, offering a new strategy for pain management.

What evidence suggests that the conditioning open-label placebo is effective for reducing opioid dosage in spinal cord injury?

This trial will compare the effects of conditioning open-label placebo (COLP) with standard opioid treatment for managing pain in individuals with spinal cord injuries. Studies have shown that COLP can reduce the need for opioids while effectively managing pain. In one study, participants using COLP reduced their opioid use by 66% compared to those who did not use it. Another trial found that open-label placebos improved pain levels, mood, and sleep in people with chronic pain. These findings suggest that COLP could help individuals with spinal cord injuries manage pain with fewer side effects and a lower risk of addiction. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8378225/

Conditioned open-label placebo for opioid reduction after ... In this randomized control trial, we investigated whether combining conditioning with an OLP (COLP) in the immediate postoperative period could reduce daily ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05351333?term=Deep%20Brain%20Stimulation&cond=Opioid%20Addiction&viewType=Table&rank=8

Conditioning & Open-Label Placebo (COLP) for Opioid ... 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 ...

3. withpower.com withpower.com/trial/phase-polytrauma-4-2022-4d73a

Open-Label Placebo for Spinal Cord Injury Opioid ... 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 ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2823541

Open-Label Placebo Injection for Chronic Back Pain With ... An open-label subcutaneous placebo (saline) injection led to significant improvements in pain intensity, mood, and sleep at 1 month posttreatment compared with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8915754/

The Use of Conditioning Open-Label Placebo in Opioid Dose ... ... spinal cord injury and polytrauma (42). Results showed that participants in the COLP group significantly reduced total opioid consumption by 66% of morphine ...

6. journals.lww.com journals.lww.com/painrpts/fulltext/2020/08000/conditioning_open_label_placebo__a_pilot.3.aspx

Conditioning open-label placebo: a pilot ... Conditioning open-label placebo (COLP) is a promising approach for reducing opioid use in comprehensive inpatient rehabilitation.