PainNCT02628314

Reliability of Pupil Response to Acute Pain

An observational study of Pain and Osteoarthritis, run by Wake Forest University Health Sciences at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this research study is to test whether researchers can reliably measure the response pupils have when an acute painful stimulus is experienced. Changes in the size of the pupil of the eye can be an indicator of brain activity in a region of the brain that is important for feeling pain. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Pain, Osteoarthritis
How many people: 20 participants
Where: 1 siteUnited States
Study dates: 4 Aug 2015to 16 Jun 2025
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Study population: Individuals with athritis in the knee or hip with moderate average daily pain score

Who may be able to join

Adult (18-70)
Pain from hip or knee arthritis of moderate intensity
American Society of Anesthesiologists physical status 1-3

Who cannot join

Inability to complete study questionnaires
Pregnancy
Litigation or workers compensation related to hip or knee pain
Taking > 50 mg morphine equivalents/day
History of Raynaud's disease of the feet
Psychotic disorder or a recent psychiatric hospitalization
History of eye surgery or topical eye medications that would would directly affect pupil diameter

Trial locations and contacts

1 site in 1 country.

United States1 site

Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Read the detailed description

There is strong rationale to support a role for locus coeruleus (LC) responsivity to acute painful stimuli in regulating speed of recovery after surgery and for LC responsivity as a mechanistic link explaining the risks for slow recovery from weak Conditioned Pain Modulation (CPM), catastrophizing cognitive style, and low enzyme activity catecholamine-O-methyltransferase (COMT) genotype. Preliminary data show feasibility to perform the proposed study.

Primary Hypothesis: An observational study of pupil responses to noxious stimuli shows strong intra-individual reliability over 8 weeks.

Key secondary hypotheses: Compared to individuals homozygous for val at the val158met site of the catecholamine-O-methyltransferase (COMT) gene, those homozygous for met will show smaller pupil responses to noxious stimuli and weaker CPM.

Conditions: Pain, Osteoarthritis
Medical subject headings: Pain, Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02628314
Study group	Role	What they receive
Osteoarthritis		Study population to include adult men and women with osteoarthritis.

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Change in Pupil Diameter
pupil diameter in response to 5 second presentation of noxious heat stimuli
Measured: 8 weeks
Pain Score on Visit 1
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.
Measured: Day 1
Pain Score on Visit 2
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.
Measured: Week 2
Pain Score on Visit 3
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.
Measured: Month 1
Pain Score on Visit 4
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.
Measured: Month 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Aug 201516 Jun 2025

First posted11 Dec 2015 (estimated)
Study start4 Aug 2015
Primary completion16 Jun 2025
Study completion16 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for PainStudies of the same condition, open and under way.
More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02628314
Sponsor's protocol ID: IRB00033891
Other IDs: 1P01GM113852
Status last verified: Apr 2026
First submitted: 8 Jul 2015
Last updated: 31 Jul 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Reliability of Pupil Response to Acute Pain
ClinicalTrials.gov ID: NCT02628314
Acronym / sponsor ID: IRB00033891
Conditions: Pain, Osteoarthritis
Study type: Observational
Recruitment status: Terminated
Enrolment: 20 participants (actual)
Lead sponsor: Wake Forest University Health SciencesUniversity, hospital or other
Collaborators: National Institute of General Medical Sciences (NIGMS)
Study start: 4 Aug 2015 (actual)
Primary completion: 16 Jun 2025 (actual)
Study completion: 16 Jun 2025 (actual)
First posted: 11 Dec 2015 (estimated)
Results: Posted 31 Jul 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Primary Hypothesis: An observational study of pupil responses to noxious stimuli shows strong intra-individual reliability over 8 weeks.

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Osteoarthritis	–	–Study population to include adult men and women with osteoarthritis.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Individuals with athritis in the knee or hip with moderate average daily pain score

Key inclusion criteria (3 listed)

Adult (18-70)
Pain from hip or knee arthritis of moderate intensity
American Society of Anesthesiologists physical status 1-3

Key exclusion criteria (7 listed)

Inability to complete study questionnaires
Pregnancy
Litigation or workers compensation related to hip or knee pain
Taking > 50 mg morphine equivalents/day
History of Raynaud's disease of the feet

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Percentage of Change in Pupil Diameter
Time frame: 8 weeks
pupil diameter in response to 5 second presentation of noxious heat stimuli
Pain Score on Visit 1
Time frame: Day 1
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.
Pain Score on Visit 2
Time frame: Week 2
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.
Pain Score on Visit 3
Time frame: Month 1
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.
Pain Score on Visit 4
Time frame: Month 2
Participants rated their pain intensity during 5 seconds of heating the skin surface to 50 degrees. They used a scale of 0-100, with 0 being no pain at all and 100 being the worst pain imaginable. The heat was applied 5 times over 7.5 minutes and these 6 scores were averaged as their individual score.

Results and safety

Results posted to the registry on 31 Jul 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Osteoarthritis	20	20

Primary outcome: Percentage of Change in Pupil Diameter

Time frame: 8 weeks

Population analysed: Calibration of the visual field using a routine in the software was not performed prior to measuring pupil diameter. Without these calibration data, pupil measurement images cannot be corrected for distortion due to gaze diverging from the center of the screen. This renders the "raw" measures of pupil diameter inaccurate. It is not possible to mathematically correct for this without calibration data.

Primary outcome: Pain Score on Visit 1

Time frame: Day 1. Mean (Standard Deviation). Unit: score on a scale

Measure	Osteoarthritis n = 20
Value	47.0 (4.4)

Primary outcome: Pain Score on Visit 2

Time frame: Week 2. Mean (Standard Deviation). Unit: score on a scale

Measure	Osteoarthritis n = 20
Value	39.3 (6.4)

Primary outcome: Pain Score on Visit 3

Time frame: Month 1. Mean (Standard Deviation). Unit: score on a scale

Measure	Osteoarthritis n = 20
Value	40.2 (8.9)

Adverse events

Time frame: 8 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Osteoarthritis	0 of 20 (0%)	0 of 20 (0%)	0 of 20

Limitations and caveats (from the sponsor): Early termination leading to small numbers of subjects analyzed: technical problems with pupil diameter measurement leading to unreliable data which were not analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James C Eisenach, MD principal investigator

Wake Forest University Health Sciences

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Pain and Osteoarthritis, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Change in Pupil Diameter (time frame: 8 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02628314.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.