Brain Effects of Opiate Agonist and Antagonist

• ClinicalTrials.gov Identifier: NCT04342130
• Recruitment Status: Completed
• First Posted: April 10, 2020
• Results First Posted: May 7, 2021
• Last Update Posted: May 7, 2021
• Sponsor: University of Rochester
• Information provided by (Responsible Party): Paul Geha, University of Rochester

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Chronic Low-back Pain	Drug: Morphine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Brain Effects of Opiate Agonist and Antagonist
• Actual Study Start Date: April 27, 2018
• Actual Primary Completion Date: April 16, 2019
• Actual Study Completion Date: April 16, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Mean Change in Subcortical Brain Structure Volume [ Time Frame: baseline to 1 hour ]
   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.
2. Change in Brain Response to Highly Caloric Drink [ Time Frame: baseline to 1 hour ]
   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.
3. Mean Change in Resting Brain Activity in the Nucleus Accumbens [ Time Frame: baseline to 1 hour ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06519

Sponsors and Collaborators

University of Rochester

Investigators

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

  Study Documents (Full-Text)

Documents provided by Paul Geha, University of Rochester:

Study Protocol and Statistical Analysis Plan  [PDF] January 5, 2018

Informed Consent Form  [PDF] August 7, 2018

More Information

• Responsible Party: Paul Geha, Assistant Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT04342130
• Other Study ID Numbers: YaleIRB#1607018141
• First Posted: April 10, 2020
• Results First Posted: May 7, 2021
• Last Update Posted: May 7, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data available from this trial will made available to researcher via reasonable request from the PI.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: study protocol and analytic code will be available after manuscript publication
• Access Criteria: Upon reasonable request from the PI

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Low Back Pain; Back Pain; Pain; Neurologic Manifestations; Morphine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents