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Pain Expectations in Subjects With Osteoarthritis

Phase 4
Completed
Conditions
Osteoarthritis
Interventions
Registration Number
NCT02155257
Lead Sponsor
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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboA placebo will be administered orally one time
ModafinilModafinilModafinil 200 mg will be administered orally one time
GabapentinGabapentinGabapentin 900 mg will be administered orally one time
Primary Outcome Measures
NameTimeMethod
Resting Pupil DiameterBaseline 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

Pain Intensity RatingReported 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.

Cognitive Stylebaseline

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Wake Forest School of Medicine

🇺🇸

Winston-Salem, North Carolina, United States

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