- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03897998
Neural Correlates of Hypoalgesia Driven by Observation
Placebo effects held an ambivalent place in health care for at least two centuries. On the one hand, placebos are traditionally used as controls in clinical trials to correct for biases and the placebo response is viewed as an effect to be factored out in order to isolate and accurately measure the effects of the treatment. On the other hand, there is scientific evidence that placebo effects represent fascinating psychoneurobiological events involving the contribution of distinct central nervous as well as peripheral physiological mechanisms that influence pain perception and clinical pain symptoms and substantially modulate the response to pain therapeutics. Therefore, placebo effects have shifted from being a challenge for clinical trials to a resource to trigger the reduction of pain based on endogenous mechanisms that can be activated in the brain to promote hypolagesia, self-healing, and well-being. This is relevant in acute pain settings given that chronic opioid users die within approximately 2.5 years of being prescribed their first opioid medication to treat acute pain.
The overall hypothesis is that observational learning influences neural pain modulation and cognition systems, including processes associated with mentalizing (the ability to cognitively understand mental states of others), empathy (the ability to share an emotional experience), and expectancy (the anticipation of a benefit). The objective is to determine the brain mechanisms of observationally-induced analgesia using brain mapping approaches that target changes in blood oxygenation and oscillatory activity in the brain, thus enabling investigators to draw inferences about the localization and extent of neurobiological activation underlying hypoalgesia driven by observation. Therefore, the investigators designed innovative experiments using pharmacological fMRI, EEG, and combined EEG-fMRI measurements.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Analgesic effects can also occur without formal conditioning and direct prior experience because crucial information necessary to build up expectations of analgesia can be acquired through observation of a therapeutic benefit in others. Placebo analgesic effects following the observation of a benefit in another person are similar in magnitude to those induced by directly experiencing an analgesic benefit. These observations emphasize that contextual cues substantially modulate the individual placebo analgesic effects.
In this project, the investigators propose a compelling research agenda to explore the neural mechanisms of hypoalgesia driven by observation as a foundation for future development of novel nonpharmacological pain therapies using pharmacological functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and combined EEG/fMRI. It builds on a decade of experience in placebo research in PI Colloca's lab and with University of Maryland collaborators experienced in brain mapping and pain research. In Aim 1, the investigators will determine the role of endogenous opioids on the neural mechanisms of observationally-induced hypoalgesia by using the opioid antagonist naloxone in a functional Magnetic Resonance Imaging (fMRI) setting. In Aim 2, the investigators will identify the impact of empathy by exploring how being in the immersive environment can enhance observationally-induced analgesia. In Aim 3, the investigators will leverage the EEG/fMRI to determine the neural EEG/fMRI transient changes that could co-occur when socially-induced expectations are violated.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Research Coordinator
- Phone Number: 410-706-5975
- Email: NRSCollocaLab@umaryland.edu
Study Contact Backup
- Name: Adria Suhr
- Email: asuhr@umaryland.edu
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21201-1512
- Recruiting
- University of Maryland
-
Contact:
- Luana Colloca
- Phone Number: 301-364-8089
- Email: colloca@umaryland.edu
-
Contact:
- Adria Suhr
- Phone Number: 4107065975
- Email: asuhr@umaryland.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age (18-55 years old)
- English speaker (written and spoken)
Exclusion Criteria:
- Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, degenerative neuromuscular disease, or history of cancer within past 3 years
- Any history of chronic pain disorder or currently in pain
- Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, mania, autism) and /or psychiatric condition leading to treatment and/or hospitalization within the last 3 years.
- Personal history of mania, schizophrenia, or other psychoses
- Nasal Polyps
- Chronic intranasal drug use ( e.g., intranasal decongestants; antihistamines)
- Lifetime alcohol/drug dependence, or alcohol/drug abuse in past 3 months
- Use of antidepressants, ADHD medication, non-over-the-counter painkillers, methadone, benzodiazepines, barbiturates, and/or narcotics during the past 3 months
- Pregnancy or breast feeding
- Color-blindness
- Impaired, uncorrected hearing
- Left handed
- Allergies or sensitivities to creams, lotions, or food coloring
- Any non-organic implant or any non-removable metal device (e.g., pacemaker, cochlear implants, stents, surgical clips, non-removable piercings)
- Any prior eye injury or the potential of a foreign body in the eye (e.g., worked in metal fields)
- Persistent functional impairment due to a head trauma
- Fear of closed spaces
- Any other contraindications for MRI (e.g., large tattoos on head and neck)
- Previously participated in other "Pain Perception in the Brain" Studies in Colloca lab Failed drug test (testing for opiates, cocaine, methamphetamines, amphetamines, and THC)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Naloxone
NARCAN® Naloxone Nasal Spray will be used to block placebo effects during the fMRI experiment.
Participants will be stratified for sex and then randomized to naloxone (The dose of naloxone will be 4 mg, so 0.1 mL of 40 mg/ml naloxone solution given intranasally) or saline (0.1 mL 0.9% sodium chloride intranasally), respectively.
Investigators, staff, and participants will be blinded to the treatment options.
|
4mg of Naloxone will be administered (0.1 mL of 40 mg/ml naloxone solution given intranasally). A random allocation sequence will be independently generated by the UM Pharmacy. The Principal investigator will call for each experiment.
Other Names:
|
Sham Comparator: Saline
Saline will be used as a sham comparator for blocking placebo effects during the fMRI experiment.
Participants will be stratified for sex and then randomized to naloxone (The dose of naloxone will be 4 mg, so 0.1 mL of 40 mg/ml naloxone solution given intranasally) or saline (0.1 mL 0.9% sodium chloride intranasally), respectively.
Investigators, staff, and participants will be blinded to the treatment options.
|
Intranasal Normal Saline (0.1 mL 0.9% sodium chloride) will be administered shortly before beginning the fMRI experiment. A random allocation sequence will be independently generated by the UM Pharmacy. The Principal investigator will call for each experiment.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neural responses
Time Frame: Two days
|
Blood oxygenation level dependent (BOLD) responses will allow the identification of relative activation/deactivation in the brain as result of events (e.g.
painful stimulations) that will be given during the experiment and the treatment administration.
|
Two days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pain ratings
Time Frame: Two days
|
Participants will rate painful and non-painful stimulations on a Visual Analogue Scale raging from 0=no pain to 100= maximum unbearable pain.
|
Two days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Luana Colloca, MD/PHD/MS, University of Maryland Baltimore School of Nursing
Publications and helpful links
General Publications
- Colloca L. The Placebo Effect in Pain Therapies. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:191-211. doi: 10.1146/annurev-pharmtox-010818-021542. Epub 2018 Sep 14.
- Schenk LA, Krimmel SR, Colloca L. Observe to get pain relief: current evidence and potential mechanisms of socially learned pain modulation. Pain. 2017 Nov;158(11):2077-2081. doi: 10.1097/j.pain.0000000000000943. No abstract available.
- Benedetti F, Pollo A, Colloca L. Opioid-mediated placebo responses boost pain endurance and physical performance: is it doping in sport competitions? J Neurosci. 2007 Oct 31;27(44):11934-9. doi: 10.1523/JNEUROSCI.3330-07.2007.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HP-00085382
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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