Brain Effects of Opiate Agonist and Antagonist

This study will look at the short-term effect of morphine on brain response to food.

Study Overview

• Status: Completed
• Conditions: Chronic Low-back Pain
• Intervention / Treatment: Drug: Morphine

Detailed Description

Chronic low back pain patients and healthy controls will be recruited for this study. Participants' brain will be scanned at baseline and then again on a different day after the administration of an oral dose of 30 mg morphine in an open label design. Participants will receive morphine 60 minutes prior to the start of the second scanning session. The brain scans will include structural scans, functional scans at rest and functional scans during the ingestion of a highly caloric drink.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy participants
• Patients in pain: suffering from persistent pain more days than not, 3/10 in intensity on a numerical rating scale, for at least 6 weeks or more.

Exclusion Criteria:

• Any DSM diagnosis
• diabetes
• food allergies
• lactose intolerance
• participants seeking to quit smoking or to lose weight
• participants on any psychotropic medication including opiate based analgesics (e.g. oxycodone, methadone, suboxone)
• pregnant or nursing women
• pacemaker or other implanted electrical devices
• Participants with a past history of head trauma or seizures
• Any past history of illegal drug or alcohol misuse
• Participants who cannot undergo an MRI scan.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All Participants; People with low back pain who were given and oral dose of 30 mg morphine.	Drug: Morphine; 30 mg oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Subcortical Brain Structure Volume	Magnetic Resonance Imaging (MRI) scanning was performed to collect brain volume measurements in cc. There were 4 different areas of the brain that were analyzed.	baseline to 1 hour
Change in Brain Response to Highly Caloric Drink	Participants received a highly caloric drink and a tasteless solution during a functional MRI scanning session. A general linear model was used to generate the magnitude of the fit for each type of stimuli and differences between the fits were calculated. A within subject analysis approach was used to calculate the effect of an acute dose of morphine on brain response to the highly caloric drink. Participants contributed beta values that were averaged across subjects and based on the average and standard deviation, the software, FSL, calculated Z = 4.38. This value indicates 4.38 standard deviations away from the mean in a distribution with a mean of zero and standard deviation of 1, which is the definition of the Gaussian curve (Z-distribution). It is scientifically not valid to say there is a higher or lower brain response. A Z-score = 0 means no change from baseline in brain response; a Z-score different from zero indicates a change from baseline after the ingestion of morphine.	baseline to 1 hour
Mean Change in Resting Brain Activity in the Nucleus Accumbens	Participants were scanned at rest during a functional MRI session. The resting brain activity was measured as the Power spectral density slow-4 frequency band. Data collected in the frequency range 0 and 0.5 Hertz was analyzed. We examined the power spectral density in the range of 0.027 to 0.073 Hertz. The mean change is expressed as arbitrary units after a Fourier transformation of the data which cancels out the units. The mean change ranges from 0 to 175. The higher the number the more energy within that frequency band.	baseline to 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Back Pain Intensity	Pain was rated using a visual analog scale ranging from 0-100 with 100 indicating the worst imaginable pain ever.	baseline to 1 hour

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Paul Geha, MD, Department of Psychiatry in University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2018
• Primary Completion (Actual): April 16, 2019
• Study Completion (Actual): April 16, 2019

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: YaleIRB#1607018141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data available from this trial will made available to researcher via reasonable request from the PI.
• IPD Sharing Time Frame: study protocol and analytic code will be available after manuscript publication
• IPD Sharing Access Criteria: Upon reasonable request from the PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No