Healthy Controls
Conditions
Brief summary
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.
Interventions
RADIATIONIntegrated MR-PET scan
Integrated MR-PET scan using \[11C\]diprenorphine
DRUGKetorolac
3 administrations of ketorolac over course of study
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| fMRI Signal Changes | one day | 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. |
| Pain Ratings | One day | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Morphine Condition Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Morphine: 3 administrations of morphine over course of study | 22 |
| Ketorolac Condition Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Ketorolac: 3 administrations of ketorolac over course of study | 29 |
| Total | 51 |
Baseline characteristics
| Characteristic | Morphine Condition | Ketorolac Condition | Total |
|---|---|---|---|
| Age, Continuous | 25.0 years STANDARD_DEVIATION 3.3 | 26.0 years STANDARD_DEVIATION 4.9 | 25.5 years STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 26 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Pain Ratings | 10.9 scores on a scale STANDARD_DEVIATION 2.6 | 11.6 scores on a scale STANDARD_DEVIATION 2.2 | 11.3 scores on a scale STANDARD_DEVIATION 2.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 23 Participants | 41 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 17 Participants | 22 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 29 |
| other Total, other adverse events | 5 / 22 | 1 / 29 |
| serious Total, serious adverse events | 0 / 22 | 0 / 29 |
Outcome results
Primary
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.
Time frame: one day
Population: Here we present the average fMRI (functional MRI) signal changes of clusters that survived a threshold of 0.005 with10 continuous voxels. We only reported beta values in pain related areas.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| fMRI Signal Change | fMRI Signal Changes | morphine injection cue at operculum | 0.82 Beta value | Standard Deviation 0.79 |
| fMRI Signal Change | fMRI Signal Changes | morphine control cue at operculum | 0.43 Beta value | Standard Deviation 0.65 |
| fMRI Signal Change | fMRI Signal Changes | ketorolac injection cue at operculum | -0.02 Beta value | Standard Deviation 0.46 |
| fMRI Signal Change | fMRI Signal Changes | ketorolac control cue at operculum | 0.55 Beta value | Standard Deviation 0.53 |
| fMRI Signal Change | fMRI Signal Changes | ketorolac injection cue at insula | 0.09 Beta value | Standard Deviation 0.42 |
| fMRI Signal Change | fMRI Signal Changes | ketorolac control cue at insula | 0.85 Beta value | Standard Deviation 0.92 |
Primary
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).
Time frame: One day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| fMRI Signal Change | Pain Ratings | -0.22 units on a scale | Standard Deviation 1.45 |
| Ketorolac Condition | Pain Ratings | -0.97 units on a scale | Standard Deviation 2.81 |