A Brain Imaging Study of Opioid (Morphine) and Non-opioid (Ketorolac) Conditioning Effects

Healthy right-handed volunteers aged 21 to 50 needed for a research study of the effects of morphine and ketorolac on brain activity in response to pain stimuli as measured by functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET). Study will be conducted on six separate days not requiring an overnight stay in the hospital.

Study Overview

• Status: Completed
• Conditions: Healthy Controls
• Intervention / Treatment: Radiation: Integrated MR-PET scan; Drug: Ketorolac

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and female adults, aged 21-50
2. No contraindications to fMRI scanning
3. Within 15% of normal BMI
4. Right handed (dominant hand is right hand)
5. Have taken an opioid drug at least once in the past (for example, after a surgery)

Exclusion Criteria:

1. Current or past history of major medical, neurological, or psychiatric illness
2. Women who are pregnant or breast feeding, have gone through menopause, or have irregular menstrual cycles (length of cycle must be within 26 to 32 days)

3. Contraindications to morphine administration:

   • i) Hypersensitivity to morphine or other phenanthrene-derivative opioid agonists (codeine, oxycodone, etc.), morphine salts, or any component of the product
   • ii) Concomitant use of other CNS depressants including antihistamines or alcohol
   • iii) History of drug or alcohol abuse
   • iv) History of head trauma
   • v) History of liver problems
   • vi) Pre-existing respiratory conditions (ex. COPD, asthma)
   • vii) Current use of any drugs that interact with morphine

4. Contraindications to ketorolac administration

   • i) Allergic-type reaction, or urticaria in response to exposure to aspirin or other NSAIDS
   • ii) Concomitant aspirin or NSAID use
   • iii) Hypersensitivity previously demonstrated to ketorolac tromethamine or to any product component
   • iv) Peptic ulcer disease (active or history), or other gastrointestinal problems
   • vi) Current use of any drugs that interact with ketorolac (ex. heparin/warfarin)
   • vii) History of bleeding disorder
   • viii) Low body weight, under 50 kg
5. Contraindications to fMRI scanning (including cardiac pacemaker, metal implants, claustrophobia, pregnancy)
6. Contraindications to either of the emergency medications (Ondansetron or Narcan)
7. History of head trauma
8. High blood pressure (>140 systolic, >90 diastolic)
9. History of impaired urinary elimination
10. Major kidney problems, bleeding problems, severe dehydration, or recovering from a recent surgery (within past year).
11. Instability of responses to experimental pain (see Study Procedures Section)
12. History of asthma
13. History of diabetes
14. Liver Function Test results greater than 2.5 times the upper limit of normal (ULN) at Screening
15. History of smoking (past or current)
16. Use of psychotropic drugs, hormone treatments (including hormonal birth control) within 1 year
17. Non-fluent speaker of English
18. Positive urine drug screen (i.e. positive on any of the 10 measures tested, including cocaine, marijuana, opiates, amphetamines, methamphetamines, phencyclidine, barbiturates, benzodiazepines, methadone, and tricyclic antidepressants)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Morphine condition	Radiation: Integrated MR-PET scan; Integrated MR-PET scan using [11C]diprenorphine
Experimental: Ketorolac condition	Radiation: Integrated MR-PET scan; Integrated MR-PET scan using [11C]diprenorphine; Drug: Ketorolac; 3 administrations of ketorolac over course of study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI Signal Changes	Obtain information about brain activity, including BOLD (Blood-oxygen-level dependent) signal, using an fMRI system. Data analysis was applied using SPM 12 with a standard pipeline.	one day
Pain Ratings	The primary endpoint was the morphine and ketorolac conditioning effects as indicated by subjective pain rating changes between pain only (a control condition with no injection of glucose, but subject's did see an image of an hour glass displaying how much time they had before receiving a painful stimulus) and pain+glucose (subjects received a glucose injection accompanied by an injection schematic followed by a painful stimulus) within the morphine and ketorolac groups. We used the Gracely pain rating scale (ranging from 0, no sensation to 20, extremely painful).	One day

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: February 24, 2012
• First Submitted That Met QC Criteria: April 10, 2012
• First Posted (Estimate): April 12, 2012

Study Record Updates

• Last Update Posted (Actual): June 29, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac
• Other Study ID Numbers: 2011P000358