Pain Expectations in Subjects With Osteoarthritis

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT02155257
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 3
• Duration (Months): 39
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Jul 1, 2014
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Modafinil Modafinil 200 mg will be administered orally one time	Drug: Modafinil; Other Names: 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 Names: Neurontin

Outcome Measures

Primary Outcome Measures

1. Resting Pupil Diameter [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest School of Medicine	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences

Investigators

• Principal Investigator: James C Eisenach, M.D., Wake Forest University Health Sciences

Study Documents (Full-Text)

• Study Protocol - Nov 6, 2014
• Statistical Analysis Plan - Nov 2, 2018

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT02155257
• Other Study ID Numbers: IRB00028525
• First Posted: Jun 4, 2014
• Last Update Posted: Mar 7, 2019
• Last Verified: Feb 1, 2019

• 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: Osteoarthritis; Knee pain; Hip pain; Total Knee Replacement Surgery
• Additional relevant MeSH terms: Osteoarthritis; Gabapentin; Modafinil

Study Results

Participant Flow

Arm/Group Title	Modafinil	Placebo	Gabapentin
Arm/Group Description	Modafinil 200 mg will be administered orally one time Modafinil	A placebo will be administered orally one time Placebo	Gabapentin 900 mg will be administered orally one time Gabapentin
Period Title: Overall Study
STARTED	10	10	10
COMPLETED	10	10	10
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Modafinil	Placebo	Gabapentin	Total
Arm/Group Description	Modafinil 200 mg will be administered orally one time Modafinil	A placebo will be administered orally one time Placebo	Gabapentin 900 mg will be administered orally one time Gabapentin	Total of all reporting groups
Overall Participants	10	10	10	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	10 100%	30 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 40%	7 70%	6 60%	17 56.7%
Male	6 60%	3 30%	4 40%	13 43.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 10%	1 3.3%
White	10 100%	10 100%	9 90%	29 96.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Resting Pupil Diameter
Description	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
Time Frame	Baseline and 2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo	Gabapentin
Arm/Group Description	Modafinil 200 mg will be administered orally one time Modafinil	A placebo will be administered orally one time Placebo	Gabapentin 900 mg will be administered orally one time Gabapentin
Measure Participants	10	10	10
Baseline	64 (11.5)	72 (12.6)	69 (12.7)
2 Hours	66.9 (11.9)	70.9 (14.5)	66.1 (13.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modafinil, Placebo, Gabapentin
	Comments	Interaction between resting pupil diameter and correlation of cognitive-affective style to pain reporting. Note that this analysis is an INTERACTION between the primary outcome of this measure (pupil diameter) to that of the primary outcome measure of cognitive-affective style.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.540
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	.19
	Confidence Interval	(2-Sided) 95%; -.39 to .76
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Pain Intensity Rating
Description	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.
Time Frame	Reported 5 seconds after each stimulus

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo	Gabapentin
Arm/Group Description	Modafinil 200 mg will be administered orally one time Modafinil	A placebo will be administered orally one time Placebo	Gabapentin 900 mg will be administered orally one time Gabapentin
Measure Participants	10	10	10
Mean (Standard Deviation) [units on a scale]	3.2 (1.7)	2.8 (1.8)	2.8 (2.0)

3. Primary Outcome

Title	Cognitive Style
Description	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.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Modafinil	Placebo	Gabapentin
Arm/Group Description	Modafinil 200 mg will be administered orally one time Modafinil	A placebo will be administered orally one time Placebo	Gabapentin 900 mg will be administered orally one time Gabapentin
Measure Participants	10	10	10
Mean (Standard Deviation) [score on a scale]	18.2 (2.3)	15.5 (2.3)	14.8 (5.7)

Adverse Events

Time Frame	2 hours
Arm/Group Title	Modafinil		Placebo		Gabapentin
Arm/Group Description	Modafinil 200 mg will be administered orally one time Modafinil		A placebo will be administered orally one time Placebo		Gabapentin 900 mg will be administered orally one time Gabapentin
All Cause Mortality
	Modafinil		Placebo		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Modafinil		Placebo		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Modafinil		Placebo		Gabapentin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.