Trial Outcomes & Findings for Effect of Ketamine on Opioid-Induced Hyperalgesia (NCT NCT00833755)

Results Overview

We measured the change in pain threshold using Quantitative Sensory Testing (QST). QST refers to a set of quantitative testing of individual responses to mechanical, thermal, and/or electrical stimulation. In this study, pain threshold was the thermal stimulation intensity (in°C) first perceived as painful. To measure this, a contact thermode was attached onto the dorsal surface of the forearm. By pressing a computer mouse button, each subject was able to stop stimulation when they first perceived a painful stimulation from the thermode as the temperature increased 1°C/s. This test was repeated 3 times and an average temperature was calculated. The temperatures could range from a minimum of 0°C to 53°C.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

79 participants

Primary outcome timeframe

Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1

Results posted on

2020-07-23

Participant Flow

Participant milestones

Participant milestones
Measure	Opioid - Ketamine Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a ketamine treatment during the study.	Opioid - Placebos Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a placebo treatment during the study.	Non-opioid - Ketamine This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a ketamine treatment.	Non-opioid - Placebos This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a placebo treatment.
Overall Study STARTED	16	18	22	23
Overall Study COMPLETED	12	13	20	17
Overall Study NOT COMPLETED	4	5	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Opioid - Ketamine Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a ketamine treatment during the study.	Opioid - Placebos Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a placebo treatment during the study.	Non-opioid - Ketamine This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a ketamine treatment.	Non-opioid - Placebos This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a placebo treatment.
Overall Study Physician Decision	4	4	2	6
Overall Study Subject had scheduling issues	0	1	0	0

Baseline Characteristics

Effect of Ketamine on Opioid-Induced Hyperalgesia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Opioid - Ketamine n=16 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a ketamine treatment during the study.	Opioid - Placebos n=18 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a placebo treatment during the study.	Non-opioid - Ketamine n=22 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a ketamine treatment.	Non-opioid - Placebos n=23 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a placebo treatment.	Total n=79 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	18 Participants n=7 Participants	22 Participants n=5 Participants	23 Participants n=4 Participants	79 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants	13 Participants n=4 Participants	46 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	10 Participants n=7 Participants	7 Participants n=5 Participants	10 Participants n=4 Participants	33 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1

Population: Only subjects who experienced pain relief after the infusion were scheduled for visit 2. This is why the overall # of participants analyzed differs from the # of baseline participants.

We measured the change in pain threshold using Quantitative Sensory Testing (QST). QST refers to a set of quantitative testing of individual responses to mechanical, thermal, and/or electrical stimulation. In this study, pain threshold was the thermal stimulation intensity (in°C) first perceived as painful. To measure this, a contact thermode was attached onto the dorsal surface of the forearm. By pressing a computer mouse button, each subject was able to stop stimulation when they first perceived a painful stimulation from the thermode as the temperature increased 1°C/s. This test was repeated 3 times and an average temperature was calculated. The temperatures could range from a minimum of 0°C to 53°C.

Outcome measures

Outcome measures
Measure	Non-opioid - Placebos n=3 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a placebo treatment.	Opioid - Ketamine n=7 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a ketamine treatment during the study.	Opioid - Placebos n=2 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a placebo treatment during the study.	Non-opioid - Ketamine n=4 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a ketamine treatment.
Change in Temperature of Pain Threshold	-0.77 Degrees Celsius Standard Deviation 1.04	-0.02 Degrees Celsius Standard Deviation 0.79	-0.61 Degrees Celsius Standard Deviation 1.79	-0.61 Degrees Celsius Standard Deviation 1.15

PRIMARY outcome

Timeframe: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1

Population: Only subjects who experienced pain relief after the infusion were scheduled for visit 2. This is why the overall # of participants analyzed differs from the # of baseline participants.

Using QST, we measured the change in pain tolerance which was the maximum thermal stimulation intensity (in °C) tolerable. In this test, the subject was instructed to press the computer mouse to stop stimulation when the thermode reached the maximal tolerable temperature. This test was repeated 3 times and an average temperature was calculated. The temperatures could range from a minimum of 0°C to 53°C.

Outcome measures

Outcome measures
Measure	Non-opioid - Placebos n=3 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a placebo treatment.	Opioid - Ketamine n=7 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a ketamine treatment during the study.	Opioid - Placebos n=2 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a placebo treatment during the study.	Non-opioid - Ketamine n=4 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a ketamine treatment.
Change in Temperature of Pain Tolerance	-0.19 Degrees Celsius Standard Deviation 1.03	-0.06 Degrees Celsius Standard Deviation 1.46	0.52 Degrees Celsius Standard Deviation 1.33	-0.42 Degrees Celsius Standard Deviation 1.95

PRIMARY outcome

Timeframe: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1

Population: Only subjects who experienced pain relief after the infusion were scheduled for visit 2. This is why the overall # of participants analyzed differs from the # of baseline participants.

Using QST, we detected the duration (seconds) of tolerance to supra-threshold heat pain stimulation. In this test, subjects were asked to tolerate, as long as he or she could, heat stimulation preset at 47°C for a maximum of 60 seconds. They were given the computer mouse to stop the test if they reached their limit before 60 seconds. If they stopped the test before the 60 seconds, the time that they stopped it was recorded. This test was repeated 3 times and an average duration was calculated. The duration could range from a minimum of 0 seconds to a maximum of 60 seconds.

Outcome measures

Outcome measures
Measure	Non-opioid - Placebos n=3 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a placebo treatment.	Opioid - Ketamine n=7 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a ketamine treatment during the study.	Opioid - Placebos n=2 Participants Subjects who have chronic pain conditions treated with an opioid regimen will be randomized to receive a placebo treatment during the study.	Non-opioid - Ketamine n=4 Participants This group will include subjects who have chronic pain conditions but not on an opioid regimen over the last 3 months. Subjects in this group will be randomized to receive a ketamine treatment.
Change in Duration of Supra-threshold Pain Tolerance	-0.39 seconds Standard Deviation 13.25	-5.22 seconds Standard Deviation 9.96	13.81 seconds Standard Deviation 19.55	-1.91 seconds Standard Deviation 7.32

Adverse Events

Opioid - Ketamine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Opioid - Placebos

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Non-opioid - Ketamine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Non-opioid - Placebos

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Jianren Mao

Massachusetts General Hospital

Phone: 6177246102

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place