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Pain Expectations in Subjects With Osteoarthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02155257
Recruitment Status : Completed
First Posted : June 4, 2014
Results First Posted : March 7, 2019
Last Update Posted : March 7, 2019
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:

The purpose of this research study is to test whether or not researchers can alter or change expectations on pain. The researchers will test whether there is an effect on the size of the pupil and responses to thermal heat temperatures in subjects with osteoarthritis of the knee or hip or healthy subjects for comparison.

One of 3 possible treatment groups will be administered to qualifying subjects: (1) gabapentin, a medication that is commonly used to treat nerve pain, (2) modafinil, a medication that is commonly used to treat people with narcolepsy (a disorder that causes people to fall asleep) and (3) a placebo, which is an inactive substance, like a sugar pill, that is not thought to have any effect on your disease or condition

Condition or disease Intervention/treatment Phase
Osteoarthritis Drug: Modafinil Drug: Gabapentin Drug: Placebo Phase 4

Detailed Description:

Purpose and rationale for this study: Both chronic pain and disability after total knee replacement surgery are predicted by negative cognitive-affective state, characterized by depression, anxiety, and a cognitive style dominated by catastrophizing. How this negative state results in chronic pain and disability is not known, but we hypothesize that it causes dysfunction of the release of the neurotransmitter, norepinephrine in several regions of the brain, mid-brain, and spinal cord that are important to many processes involved in recovery from surgery.

Objectives: (1) Gabapentin and modafinil will increase resting pupil diameter with a moderate effect size in patients with osteoarthritis; (2) Expectations will modify pain experience with a moderate effect size in these patients

Methods: 30 subjects with moderate average daily pain from osteoarthritis of the knee or hip or healthy subjects will be recruited and will come to the clinical research unit at Wake Forest. Informed consent will be confirmed and they will complete the questionnaires. We will take a verbal medical and medication history and obtain blood pressure and heart rate measurements. Verbal pain intensity report (0-10 from no pain to worst pain imaginable) will be obtained from a 5 second heat stimuli, separated by 30 seconds, delivered to a nonpainful area of skin on the arm as described in preliminary data. During pain testing, study subjects will sit in a comfortable chair in a low-ambient light room with their head positioned on a chin rest for continuous recording of pupil diameter using a near infrared recording system as described in preliminary data. Pupil diameter and probe temperature will be passed through an analog to digital converter and acquired at 60 Hertz (Hz) for subsequent analysis.

Five sequences of test stimuli will be presented, with a brief break in between each sequence. The first sequence will consist of 7 stimuli, from 39⁰ to 51⁰ Celsius (C) in 2⁰C increments, in ascending order. Data from this training sequence will not be used for analysis. Sequences 2 and 3 will consist of 5, 5-second stimuli, presented in random order, to generate moderate (50⁰C) and mild (47⁰C) pain (random condition). Sequences 4 and 5 will also consist of random presentation of 5 stimuli at these temperatures, but with different auditory tones 6 s prior to stimulus onset to correctly cue the stimulus temperature (cued condition).

Subjects will then be randomized to receive oral gabapentin, 900 milligram (mg), modafinil, 200 mg, or placebo, followed 2 hours later by pain testing with pupillometry, consisting of different sequences. The random and cued paradigms will be presented twice each followed by a sequence with one miscue in the positive expectation for pain direction (signal for 50⁰C but deliver 47⁰C) and one in the negative expectation for pain direction. Subjects will provide verbal pain intensity scores after each stimulus.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Feasibility Study: Understanding and Altering Pain Expectations in Subjects With Osteoarthritis of the Knee or Hip
Study Start Date : July 2014
Actual Primary Completion Date : October 2017
Actual Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Active Comparator: Modafinil
Modafinil 200 mg will be administered orally one time
Drug: Modafinil
Other Name: Provigil

Placebo Comparator: Placebo
A placebo will be administered orally one time
Drug: Placebo
Active Comparator: Gabapentin
Gabapentin 900 mg will be administered orally one time
Drug: Gabapentin
Other Name: Neurontin

Primary Outcome Measures :
  1. Resting Pupil Diameter [ Time Frame: Baseline and 2 hours ]
    Resting pupil diameter will be measured using an infrared camera to obtain baseline measurements 2 hours after dosing subject pupil diameter measurements will be repeated

  2. Pain Intensity Rating [ Time Frame: Reported 5 seconds after each stimulus ]
    Pain is reported verbally after each stimulus by the subject on a scale of 0 (no pain) to 10 (worst imagineable pain). For each individual the value used is the average of all presentations of the 50 degree stimulus.

  3. Cognitive Style [ Time Frame: baseline ]
    Cognitive style determined for each individual by subtracting the score in the Pain Catastrophizing Scale (CATS) questionnaire (with a score range of 0-52 with higher score showing more catastrophizing) from the Life Orientation Test Revised (LOT-R) questionnaire (score range of 0-24, with a higher score denoting a better outcome). Thus, the total score could range from ranges from -52 to 24, with lower scores indicating worse cognitive style related to pain reporting and higher scores indicating better cognitive style related to pain reporting. There are no subscales here.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Osteoarthritis of the knee or hip
  • Adult (ages 18-80)
  • Moderate pain (verbal score of ≥ 4 ≤ 7 on 0-10 scale for average pain intensity with normal activity)
  • American Society of Anesthesiologists physical status 1-3
  • Healthy subjects without pain

Exclusion Criteria:

  • Pregnancy;
  • Currently taking gabapentin
  • Currently taking a narcotic prescription medication that is > 50 mg morphine equivalents/day
  • Advanced or unstable cardiac, pulmonary, renal or hepatic dysfunction
  • History of previous eye surgery
  • Psychotic disorder or a recent psychiatric hospitalization

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02155257

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United States, North Carolina
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
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Principal Investigator: James C Eisenach, M.D. Wake Forest University Health Sciences
  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:
Study Protocol  [PDF] November 6, 2014
Statistical Analysis Plan  [PDF] November 2, 2018

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Responsible Party: Wake Forest University Health Sciences Identifier: NCT02155257    
Other Study ID Numbers: IRB00028525
First Posted: June 4, 2014    Key Record Dates
Results First Posted: March 7, 2019
Last Update Posted: March 7, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Wake Forest University Health Sciences:
Knee pain
Hip pain
Total Knee Replacement Surgery
Additional relevant MeSH terms:
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Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Central Nervous System Stimulants
Wakefulness-Promoting Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers