Trial Outcomes & Findings for A Brain Imaging Study of Opioid (Morphine) and Non-opioid (Ketorolac) Conditioning Effects (NCT NCT01576276)
NCT ID: NCT01576276
Last Updated: 2018-06-29
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
51 participants
Primary outcome timeframe
one day
Results posted on
2018-06-29
Participant Flow
Participant milestones
| Measure |
Morphine Condition
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Morphine: 3 administrations of morphine over course of study
|
Ketorolac Condition
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Ketorolac: 3 administrations of ketorolac over course of study
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
29
|
|
Overall Study
COMPLETED
|
14
|
18
|
|
Overall Study
NOT COMPLETED
|
8
|
11
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Some subjects were dropped before or during the MRI scan in which baseline pain ratings were collected. We used the Gracely Sensory Pain Scale (0-20; 0: no pain, 20: intolerable pain) to rate the pain subject's experienced.
Baseline characteristics by cohort
| Measure |
Morphine Condition
n=22 Participants
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Morphine: 3 administrations of morphine over course of study
|
Ketorolac Condition
n=29 Participants
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Ketorolac: 3 administrations of ketorolac over course of study
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
25.0 years
STANDARD_DEVIATION 3.3 • n=22 Participants
|
26.0 years
STANDARD_DEVIATION 4.9 • n=29 Participants
|
25.5 years
STANDARD_DEVIATION 4.0 • n=51 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=22 Participants
|
7 Participants
n=29 Participants
|
12 Participants
n=51 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=22 Participants
|
22 Participants
n=29 Participants
|
39 Participants
n=51 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=22 Participants
|
2 Participants
n=29 Participants
|
3 Participants
n=51 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=22 Participants
|
26 Participants
n=29 Participants
|
45 Participants
n=51 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=22 Participants
|
1 Participants
n=29 Participants
|
3 Participants
n=51 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=22 Participants
|
0 Participants
n=29 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=22 Participants
|
1 Participants
n=29 Participants
|
4 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=22 Participants
|
0 Participants
n=29 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=22 Participants
|
1 Participants
n=29 Participants
|
2 Participants
n=51 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=22 Participants
|
23 Participants
n=29 Participants
|
41 Participants
n=51 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=22 Participants
|
3 Participants
n=29 Participants
|
3 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=22 Participants
|
1 Participants
n=29 Participants
|
1 Participants
n=51 Participants
|
|
Pain Ratings
|
10.9 scores on a scale
STANDARD_DEVIATION 2.6 • n=14 Participants • Some subjects were dropped before or during the MRI scan in which baseline pain ratings were collected. We used the Gracely Sensory Pain Scale (0-20; 0: no pain, 20: intolerable pain) to rate the pain subject's experienced.
|
11.6 scores on a scale
STANDARD_DEVIATION 2.2 • n=18 Participants • Some subjects were dropped before or during the MRI scan in which baseline pain ratings were collected. We used the Gracely Sensory Pain Scale (0-20; 0: no pain, 20: intolerable pain) to rate the pain subject's experienced.
|
11.3 scores on a scale
STANDARD_DEVIATION 2.4 • n=32 Participants • Some subjects were dropped before or during the MRI scan in which baseline pain ratings were collected. We used the Gracely Sensory Pain Scale (0-20; 0: no pain, 20: intolerable pain) to rate the pain subject's experienced.
|
PRIMARY outcome
Timeframe: one dayPopulation: 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.
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.
Outcome measures
| Measure |
fMRI Signal Change
n=33 Participants
We used SPM 12 to analyze the data, and compared the fMRI signal change during pressure pain between 1. morphine injection cue vs. control cue, 2. ketorolac injection cue vs. control cue. A threshold of p \< 0.005 with 10 continuous voxels was applied.
|
Ketorolac Condition
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Ketorolac: 3 administrations of ketorolac over course of study
|
|---|---|---|
|
fMRI Signal Changes
ketorolac injection cue at insula
|
0.09 Beta value
Standard Deviation 0.42
|
—
|
|
fMRI Signal Changes
morphine injection cue at operculum
|
0.82 Beta value
Standard Deviation 0.79
|
—
|
|
fMRI Signal Changes
morphine control cue at operculum
|
0.43 Beta value
Standard Deviation 0.65
|
—
|
|
fMRI Signal Changes
ketorolac injection cue at operculum
|
-0.02 Beta value
Standard Deviation 0.46
|
—
|
|
fMRI Signal Changes
ketorolac control cue at operculum
|
0.55 Beta value
Standard Deviation 0.53
|
—
|
|
fMRI Signal Changes
ketorolac control cue at insula
|
0.85 Beta value
Standard Deviation 0.92
|
—
|
PRIMARY outcome
Timeframe: One dayThe 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).
Outcome measures
| Measure |
fMRI Signal Change
n=14 Participants
We used SPM 12 to analyze the data, and compared the fMRI signal change during pressure pain between 1. morphine injection cue vs. control cue, 2. ketorolac injection cue vs. control cue. A threshold of p \< 0.005 with 10 continuous voxels was applied.
|
Ketorolac Condition
n=18 Participants
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Ketorolac: 3 administrations of ketorolac over course of study
|
|---|---|---|
|
Pain Ratings
|
-0.22 units on a scale
Standard Deviation 1.45
|
-0.97 units on a scale
Standard Deviation 2.81
|
Adverse Events
Morphine Condition
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Ketorolac Condition
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Morphine Condition
n=22 participants at risk
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Morphine: 3 administrations of morphine over course of study
|
Ketorolac Condition
n=29 participants at risk
Integrated MR-PET scan: Integrated MR-PET scan using \[11C\]diprenorphine
Ketorolac: 3 administrations of ketorolac over course of study
|
|---|---|---|
|
Surgical and medical procedures
Drug related reactions
|
22.7%
5/22 • Number of events 5 • Adverse event data was collected for each participant over a 3 hours period (from time of drug administration until they left 3 hours later). We collected this for every participant throughout our study.
Our definitions are consistent. After every drug administration we asked a standard questionnaire, which we also asked again a couple of hours following the initial drug administration. Specifically, we asked subjects if they felt nauseous, indigestion, itching, spacey/drugged, lightheadedness/faint, sense of difficulty concentrating, or sleepy.
|
3.4%
1/29 • Number of events 1 • Adverse event data was collected for each participant over a 3 hours period (from time of drug administration until they left 3 hours later). We collected this for every participant throughout our study.
Our definitions are consistent. After every drug administration we asked a standard questionnaire, which we also asked again a couple of hours following the initial drug administration. Specifically, we asked subjects if they felt nauseous, indigestion, itching, spacey/drugged, lightheadedness/faint, sense of difficulty concentrating, or sleepy.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place