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Effect of Ketamine on Opioid-Induced Hyperalgesia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Jianren Mao, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00833755
First received: January 29, 2009
Last updated: June 19, 2014
Last verified: June 2014
  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: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Health Services Research
Official Title: Effect of Ketamine on Opioid-Induced Hyperalgesia

Resource links provided by NLM:


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 ]

Estimated Enrollment: 136
Study Start Date: September 2008
Estimated Study Completion Date: December 2015
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
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.
Active Comparator: 2
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.

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Jianren Mao, M.D., Ph.D. Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Jianren Mao, MD, PhD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00833755     History of Changes
Other Study ID Numbers: 2008P 000879
Study First Received: January 29, 2009
Last Updated: June 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Pain
Chronic pain
Opioid induced hyperalgesia
Opioid therapy

Additional relevant MeSH terms:
Chronic Pain
Hyperalgesia
Nervous System Diseases
Neurologic Manifestations
Pain
Sensation Disorders
Signs and Symptoms
Somatosensory Disorders
Ketamine
Analgesics
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014