Effect of Ketamine on Opioid-Induced Hyperalgesia

NCT00833755 | Completed Results DMC

• 1 other identifier: 2008P 000879
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain; Chronic Pain; Hyperalgesia

Keywords

Pain; Chronic pain; Opioid induced hyperalgesia; Opioid therapy

Outcome Measures

Primary Outcomes (3)

• Change in Temperature of Pain Threshold

  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.

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

• Change in Temperature of Pain Tolerance

  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.

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

• Change in Duration of Supra-threshold Pain Tolerance

  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.

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

Study Arms (4)

Opioid - Ketamine

ACTIVE COMPARATOR

This group consists of 16 subjects who have chronic pain conditions treated with an opioid regimen. Subjects were randomized to receive a ketamine treatment during the study. They were given an intravenous infusion of ketamine (0.05mg/kg) diluted in 50 ml normal saline over 30 minutes.

Drug: Ketamine

Non-opioid - Ketamine

ACTIVE COMPARATOR

This group consists of 22 subjects who have chronic pain conditions but were not on an opioid regimen over the last 3 months. Subjects were randomized to receive a ketamine treatment during the study. They were given an intravenous infusion of ketamine (0.05mg/kg) diluted in 50 ml normal saline over 30 minutes.

Drug: Ketamine

Opioid - Placebos

PLACEBO COMPARATOR

This group consists of 18 subjects who have chronic pain conditions treated with an opioid regimen. Subjects were randomized to receive a placebo treatment during the study. They were given an intravenous infusion of 50 ml normal saline over 30 minutes.

Drug: Placebos

Non-opioid - Placebos

PLACEBO COMPARATOR

This group consists of 23 subjects who have chronic pain conditions but were not on an opioid regimen over the last 3 months. Subjects were randomized to receive a placebo treatment during the study. They were given an intravenous infusion of 50 ml normal saline over 30 minutes.

Drug: Placebos

Interventions

Ketamine DRUG

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.

Also known as: Ketalar

Non-opioid - Ketamine; Opioid - Ketamine

Placebos DRUG

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.

Also known as: Saline

Non-opioid - Placebos; Opioid - Placebos

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject will be between ages 18 to 65 years.
• 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.
• 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.
• Subject who meets the criteria #1 \& #2 as listed for Group 1.
• Subject has not been on an opioid regimen for the last three or more months.

You may not qualify if:

• Subject has an altered sensation at the skin site of QST (one of upper extremities).
• Subject has scar tissue or acute injury at the skin site of QST.
• 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.
• Subject has a diagnosis of renal or liver failure.
• Subject has a diagnosis of unstable angina, congestive heart failure, cardiac arrythmias or myocardial infarction within 1 year.
• Subject is allergic to ketamine.
• 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.
• 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
• Subject is tested positive on drug urine screening test.
• Subject is pregnant or breast-feeding.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• 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.

  PMID: 28842370 DERIVED

• 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.

  PMID: 28802882 DERIVED

Related Links

• MGH Center for Translational Pain Research

MeSH Terms

Conditions

Pain; Chronic Pain; Hyperalgesia

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Jianren Mao
• Organization: Massachusetts General Hospital

mghpainresearch@partners.org

6177246102

Study Officials

• Jianren Mao, M.D., Ph.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 29, 2009
• First Posted: February 2, 2009
• Study Start: September 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: April 1, 2016
• Last Updated: July 23, 2020
• Results First Posted: January 16, 2017

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)