Neuroimmune Effects of Opioid Administration

NCT03801629 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2000024785
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Preclinical research indicates acute opioid administration evokes an immune response in the periphery and brain. Here, we will translate those preclinical findings to healthy human volunteers and quantify the neuroimmune response to a morphine challenge using positron emission tomography (PET) imaging with \[11C\]PBR28.

Conditions

Drug Effect

Keywords

Neuroimmune System; Morphine; PET Imaging; TSPO

Outcome Measures

Primary Outcomes (1)

• Change in Brain TSPO availability

  Relative to pre-morphine levels, we will measure the change in brain regional TSPO availability (VT) after morphine. VT will be calculated for brain regions of interest using multi-linear analysis 1 (t\*=30) using the metabolite-corrected arterial input function.

  One 120-minute PET [11C]PBR28 scan before and one PET [11C]PBR28 scan 2hr after morphine challenge.

Secondary Outcomes (17)

• Change in Verbal Learning Performance

  This Cogstate task will be administered twice: once before and once ~40 minutes after the morphine challenge.

• Change in Verbal Memory Performance

  This Cogstate task will be administered twice: once before and once ~70 minutes after the morphine challenge.

• Change in Psychomotor Speed

  This Cogstate task will be administered twice: once before and once ~45 minutes after the morphine challenge.

• Change in Visual Attention

  This Cogstate task will be administered twice: once before and once ~50 minutes after the morphine challenge.

• Change in Visual Learning

  This Cogstate task will be administered twice: once before and once ~55 minutes after the morphine challenge.

Other Outcomes (4)

• Change in systolic blood pressure

  Blood pressure will be measured 10-minutes before, and 30-minutes, 60-minutes, and 90-minutes after morphine.

• Change in diastolic blood pressure

  Blood pressure will be measured 10-minutes before, and 30-minutes, 60-minutes, and 90-minutes after morphine.

• Change in heart rate

  Heart rate will be measured 10-minutes before, and 30-minutes, 60-minutes, and 90-minutes after morphine.

Study Arms (2)

High Morphine Dose

EXPERIMENTAL

Subjects in this experimental arm will receive a single intramuscular morphine dose (non-dominant deltoid muscle; 0.07 mg/kg).

Drug: High Morphine Dose

Low Morphine Dose

EXPERIMENTAL

Subjects in this experimental arm will receive a single intramuscular morphine dose (non-dominant deltoid muscle; 0.04 mg/kg).

Drug: Low Morphine Dose

Interventions

High Morphine Dose DRUG

Subjects will receive an intramuscular morphine injection (0.07mg/kg) in the non-dominant deltoid muscle. Metoclopramide (10mg; oral) will be administered PRN to reduce nausea.

Also known as: High Dose

High Morphine Dose

Low Morphine Dose DRUG

Subjects will receive an intramuscular morphine injection (0.04mg/kg) in the non-dominant deltoid muscle. Metoclopramide (10mg; oral) will be administered PRN to reduce nausea.

Also known as: Low Dose

Low Morphine Dose

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged between 21 and 50 years (driver's license or valid state ID).
• Physically healthy by medical history, physical, neurological, EKG and laboratory examinations (reviewed by the Study Physician).
• Normal weight, as indicated by a body mass index (BMI) and body weight ≤ 250lbs.
• Read, comprehend, and write English at a sufficient level to complete study-related materials.
• Able to provide voluntary and written informed consent.
• Eligibility and willingness to participate in study procedures, including MRI and PET scanning.
• Previous medical use of opioids without adverse reactions (≥2 lifetime uses).

You may not qualify if:

• Medically eligible to receive 10mg of oral metoclopramide based on medical history, medical exams, and current medications.
• Any DSM-5 Axis I disorder diagnosis based on Structured Clinical Interview for DSM-5 (SCID-5), including meeting criteria for substance dependence.
• Any current psychotropic medication use, including MAOI use within the past 14 days
• Recent (past 6 months) medical or non-medical opioid-use.
• Prior medical use prescription opioids for \>14 consecutive days (self-report)
• Prior non-medical use of any opioid (i.e., recreational opioid use will be excluded).
• Positive result on a urine drug screen (excluding marijuana).
• Current or previous chronic pain disorder (\>6 months of continuous pain).
• 'Low affinity binding' individuals based on rs6971 polymorphism (\<10% of the population).
• For females, pregnancy (positive urine test).
• Current use of non-steroidal anti-inflammatory medications or statins.
• Medical contraindication to receive up to 0.1 mg/kg intramuscular morphine administration as determined by Study Physician. This includes:
• known hypersensitivity/allergy to morphine;
• acute or severe bronchial asthma;
• known or suspected gastrointestinal obstruction, including paralytic ileus;

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Cosgrove Lab

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Interventions

Contraceptives, Oral

Intervention Hierarchy (Ancestors)

Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses

Study Officials

• Eric Woodcock, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

• Kelly Cosgrove, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects are informed that they will receive a single morphine injection. Subjects are blinded to the morphine dose condition. Investigators and assessors are not blinded to morphine dose condition.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Research Scientist

Model Details: Subjects will receive a single intramuscular morphine dose: 'High' (0.07mg/kg i.m.) vs. 'Low' (0.04mg/kg i.m.)

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 11, 2019
• Study Start: September 12, 2019
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: April 27, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Study supporting information will be available upon reasonable request after publication of the primary manuscript.
• Access Criteria: Available to research scientists and clinicians for academic uses only.

Locations

US (1)