Clinical trial NCT00833755: Effect of Ketamine on Opioid-Induced Hyperalgesia
Official title: Effect of Ketamine on Opioid-Induced Hyperalgesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain
Chronic Pain
Hyperalgesia
Keywords: Pain
Chronic pain
Opioid induced hyperalgesia
Opioid therapy
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2009-02-02
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The purpose of this study is to compare pain threshold, pain tolerance, and wind up, as measured by QST, before and after a single dose of ketamine infusion under two clinical conditions: chronic pain patients on opioid therapy and chronic pain patients without opioid therapy.

Detailed description: We hypothesize that:

1. Chronic pain patients on chronic opioids would have a lower pain threshold and lower pain tolerance when compared to opioid naïve patients (patients with chronic pain with non-opioids treatment)., as measured by QST in a non-affected neutral limb;
2. Chronic pain patients on chronic opioids would have an increased response to painful stimulation, so called "windup" as demonstrated by QST;
3. Both "wind-up" and altered pain threshold and tolerance would be indicative of the presence of opioid-induced hyperalgesia;
4. Intravenous ketamine, an NMDA receptor antagonist, could be used to differentiate between opioid-induced hyperalgesia and opioid tolerance.

Eligibility criteria: Inclusion Criteria for Group 1

1. Subject will be between ages 18 to 65 years.
2. Subject has a chronic pain condition for at least three months. This requirement is set in order to avoid the clinical uncertainty of an unstable pain condition and to minimize the study variation. Subjects should have a VAS pain score at 4 or above at the time of study.
3. Subject is on a chronic opioid treatment regimen (e.g., morphine, fentanyl, oxycodone, methadone, hydromorphone, hydrocodone) for at least three months. There should have been no changes in the type and amount of opioid dose for at least one month. Only patients with a minimal daily dose of at least 60 mg morphine equianalgesic dose will be included.

Inclusion Criteria for Group 2

1. Subject who meets the criteria #1 \& #2 as listed for Group 1.
2. Subject has not been on an opioid regimen for the last three or more months.

Exclusion Criteria for all groups:

1. Subject has an altered sensation at the skin site of QST (one of upper extremities).
2. Subject has scar tissue or acute injury at the skin site of QST.
3. Subject has neurological disease or a condition causing upper extremities or generalized polyneuropathy, such as diabetic neuropathy, alcoholic neuropathy, AIDS neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, and post-stroke residual neurological deficits.
4. Subject has a diagnosis of renal or liver failure.
5. Subject has a diagnosis of unstable angina, congestive heart failure, cardiac arrythmias or myocardial infarction within 1 year.
6. Subject is allergic to ketamine.
7. Subject had recent therapy that may influence QST results, e.g., neuroablative procedure involving upper extremities within six-months or peripheral neurolytic block involving upper extremities within two-months.
8. Subject has a confirmed diagnosis of and is under the care of a psychiatrist for major depression disorder, eating disorder; alcohol or drug dependence; or attention deficit hyperactivity disorder. Subject has any history of a confirmed diagnosis of bipolar disorder, schizophrenia, anxiety disorder or a psychotic disorder
9. Subject is tested positive on drug urine screening test.
10. Subject is pregnant or breast-feeding.

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Primary outcomes:
measure: Change in Temperature of Pain Threshold
timeFrame: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1
measure: Change in Temperature of Pain Tolerance
timeFrame: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1
measure: Change in Duration of Supra-threshold Pain Tolerance
timeFrame: Baseline at visit 1, post inufsion at visit 1, and at visit 2 which was 1 week after visit 1
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Jianren Mao, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Luna IE, Kehlet H, Jensen CM, Christiansen TG, Lind T, Stephensen SL, Aasvang EK. The Effect of Preoperative Intra-Articular Methylprednisolone on Pain After TKA: A Randomized Double-Blinded Placebo Controlled Trial in Patients With High-Pain Knee Osteoarthritis and Sensitization. J Pain. 2017 Dec;18(12):1476-1487. doi: 10.1016/j.jpain.2017.07.010. Epub 2017 Aug 24.
citation: Maher DP, Zhang Y, Ahmed S, Doshi T, Malarick C, Stabach K, Mao J, Chen L. Chronic Opioid Therapy Modifies QST Changes After Ketamine Infusion in Chronic Pain Patients. J Pain. 2017 Dec;18(12):1468-1475. doi: 10.1016/j.jpain.2017.07.008. Epub 2017 Aug 10.