Effect of Ketamine on Opioid-Induced Hyperalgesia - Full Text View

Sponsored by:	Massachusetts General Hospital
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00833755

Purpose

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.

Condition	Intervention
Pain Chronic Pain Hyperalgesia	Drug: Ketamine

Study Type:	Observational
Study Design:	Case-Only, Prospective
Official Title:	Effect of Ketamine on Opioid-Induced Hyperalgesia

Resource links provided by NLM:

Drug Information available for: Ketamine hydrochloride Ketamine

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Intravenous ketamine, an NMDA receptor antagonist, could be used to differentiate between opioid-induced hyperalgesia and opioid tolerance. [ Time Frame: After completion of study. ] [ Designated as safety issue: No ]

Biospecimen Retention: None Retained

Biospecimen Description:

Estimated Enrollment:	136
Study Start Date:	September 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
1 Group 1: 90 subjects who have chronic pain conditions treated with an opioid regimen. Subjects will be randomized to receive either a ketamine (45 subjects) or a placebo (45 subjects) treatment during the study. Group2: This group will include 46 subjects who have chronic pain conditions similar to those in Group 1 but not on an opioid regimen over the last 3 months. Subjects in this group also will be randomized to receive either ketamine (23 subjects) or a placebo (23 subjects) treatment.	Drug: Ketamine 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.
2	Drug: Ketamine 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.

Groups/Cohorts

Assigned Interventions

1

Group 1: 90 subjects who have chronic pain conditions treated with an opioid regimen. Subjects will be randomized to receive either a ketamine (45 subjects) or a placebo (45 subjects) treatment during the study. Group2: This group will include 46 subjects who have chronic pain conditions similar to those in Group 1 but not on an opioid regimen over the last 3 months. Subjects in this group also will be randomized to receive either ketamine (23 subjects) or a placebo (23 subjects) treatment.

Drug: Ketamine

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.

2

Drug: Ketamine

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:

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;
Chronic pain patients on chronic opioids would have an increased response to painful stimulation, so called "windup" as demonstrated by QST;
Both "wind-up" and altered pain threshold and tolerance would be indicative of the presence of opioid-induced hyperalgesia;
Intravenous ketamine, an NMDA receptor antagonist, could be used to differentiate between opioid-induced hyperalgesia and opioid tolerance.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Subjects with chronic pain

Criteria

Inclusion Criteria for Group 1

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.

Inclusion Criteria for Group 2

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.

Exclusion Criteria for all groups:

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.

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Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00833755

Contacts

Contact: Mary Houghton, B.A.	617-726-3744	mhoughton1@partners.org
Contact: Charlene Malarick, R.N.	617-724-0253	cmalarick@partners.org

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Jianren Mao, M.D., Ph.D.

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

Principal Investigator:

Jianren Mao, M.D., Ph.D.

Massachusetts General Hospital

More Information

Additional Information:

MGH Center for Translational Pain Research This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Massachusetts General Hospital ( Dr. Jianren Mao, Principal Investigator )
Study ID Numbers:	2008-P-000879
Study First Received:	January 29, 2009
Last Updated:	July 27, 2009
ClinicalTrials.gov Identifier:	NCT00833755 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

Pain
Chronic pain
Opioid induced hyperalgesia
Opioid therapy

Study placed in the following topic categories:

Anesthetics, Intravenous
Excitatory Amino Acids
Sensation Disorders
Neurotransmitter Agents
Central Nervous System Depressants
Anesthetics
Pain
Hyperalgesia
Anesthetics, Dissociative

Somatosensory Disorders
Signs and Symptoms
Anesthetics, General
Ketamine
Neurologic Manifestations
Peripheral Nervous System Agents
Analgesics
Analgesics, Opioid

Additional relevant MeSH terms:

Anesthetics, Intravenous
Sensation Disorders
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Nervous System Diseases
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Agents
Hyperalgesia
Pharmacologic Actions
Anesthetics, Dissociative

Somatosensory Disorders
Signs and Symptoms
Sensory System Agents
Anesthetics, General
Therapeutic Uses
Ketamine
Neurologic Manifestations
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Analgesics, Opioid
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on August 28, 2009