Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01254201 |
| Other study ID # |
HUM00013091 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
December 3, 2010 |
| Last updated |
March 13, 2017 |
| Start date |
June 2008 |
| Est. completion date |
December 2015 |
Study information
| Verified date |
March 2017 |
| Source |
University of Michigan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Dry eyes are a very common complaint. In some patients, we can identify the reason for the
dryness; however, in others the dryness has no clear cause. Dryness can lead to eye
irritation, redness, and sometimes changes in vision. Fibromyalgia is a condition of chronic
pain that is poorly understood but seems to have a component of altered sensory processing.
People with fibromyalgia tend to complain of dry and irritated eyes at a higher rate than
the general population. We plan to evaluate patients with dry eye symptoms for abnormalities
in sensory processing and in their autonomic nervous system. We hope to learn about possible
relationships between dry eye symptoms and fibromyalgia in order to better understand and
treat these conditions.
Description:
Dry eye and fibromyalgia syndromes are most prevalent in women. Therefore, female patients
seen in Kellogg Eye Center for ocular complaints of dryness, grittiness, irritation, or
related symptoms, without any identifiable cause, will be offered enrollment into the study.
These individuals will be compared to both a "positive control" group (fibromyalgia
patients) and a healthy control group. We hypothesize that the patients seen with irritative
symptoms will have autonomic and sensory processing profiles similar to fibromyalgia
patients, and both groups will differ from healthy controls. All study participants will
have an extensive ophthalmological exam in addition to autonomic and sensory testing, in
order to more fully characterize the underlying mechanism(s) of these symptoms.
Recruitment:
Female patients over the age of 18 with the above mentioned complaints will be told of the
study at the time of their visit. They will be given a copy of the study consent form to
take home with them or one will be mailed to them. Additionally, from CareWeb billing
records, or from other University of Michigan Ophthalmologists, a list of patients who have
previously been seen (within the last year) in the Ophthalmology Comprehensive Clinic for
dry eyes complaints will be identified and contacted by US mail with a recruitment letter
uploaded. If the patient is interested, the letter will list research staff contact
information, who patients may then contact. If the patient does not contact research staff
by phone or email, research staff may follow-up the letter by phone no earlier than one week
after it is mailed. If patients are not interested, a phone number will be listed allowing
patients to opt-out of being contacted about the study by phone in the future. Follow-up
phone calls will utilize a phone script.
Patients who are interested in participating will be contacted by the study coordinator for
further discussion to see if they meet the inclusion and exclusion criteria and to schedule
a visit to the Cornea Clinic for an ophthalmic evaluation. At the time of this visit,
patients will be asked to sign the consent form and be given a study identification number
that will be used exclusively in patient identification in study materials. These patients
will then be scheduled to be seen at the Chronic Pain and Fatigue Research Center at Dominos
Farms for the remaining sensory and autonomic testing. All patient study information will be
collected and encoded according to HIPAA guidelines and institutional review board approval.
The plan is to enroll 50 patients into Group 1 over a 12 month enrollment period.
The study group will be compared to two groups of age matched patients, 25 with known FM
(Group 2) and 25 healthy controls (Group 3). These patients will be identified by searching
the patient registry that includes more than 400 FM and healthy control patients who have
already undergone the standardized sensory and autonomic evaluations at the Chronic Pain and
Fatigue Research Center. The study coordinator will then contact the individuals that are
identified in the registry that meet these criteria, and they will be asked if they are
interested in enrolling in this particular study (all individuals in the registry have given
consent to be contacted for additional studies for which they are eligible). FM patients and
controls who agree to participate will be asked to sign the consent form and be scheduled
for the ophthalmic evaluation at the Cornea Clinic.
Ophthalmic Evaluation:
Individuals in all three groups will be seen in the Cornea Clinic at the Kellogg Eye Center
and will receive a complete ophthalmic evaluation including the following objective measures
of ocular and visual sensation:
- Visual acuity will be assessed in each eye separately, using a Snellen acuity chart for
distance and a Jaegar reading card for near vision. Additional notations will be made
for subjective evaluation of patient's level of satisfaction with corrected acuity
during testing.
- Shirmer's testing with anesthesia will be performed on all patients. This test involves
the use of small strips of filter paper placed in the lower eyelids after instillation
of anesthetic eyedrops for the assessment of tear production.
- Corneal fluorescein and conjunctival lissamine green staining patterns will be assessed
as a measure of ocular surface integrity. Staining will be measured using the Oxford
grading scale from 0 (no staining) to 5 (severe staining)
- Tear break up time is evaluated while fluorescein stain is still in the eye. The
patient is instructed not to blink and the tear film is observed through the slit lamp.
If the smooth layer tear film begins to visibly break up prior to 10 seconds, the
patient's tear film is considered abnormal.
- Ocular complaints will be quantified with the use of the Ocular Surface Disease Index
Questionnaire - a validated 15 question survey that evaluates dry eye symptoms as well
as the National Eye Institute Visual Functioning Questionnaire - a validated 25
question survey that evaluates overall visual function.
- Accommodation, or the ability to shift visual focus from distance to near, will be
measured with the Marco auto-refractor separately for each eye. Accommodation is a
physiologic measure of the eye's ability to shift focus and naturally decreases with
age.
- Central corneal sensation will be measured using Cochet-Bonnet esthesiometry. The
esthesiometer is an instrument that comprises a slender nylon filament that is
retracted in 0.5 cm increments until the filament is sensed on the cornea.
- Confocal Microscopy - The patients' eyes will be viewed using a high power microscope
to carefully evaluate the corneal nerve layer. This microscope looks at the layers of
the cornea (or window) of the eye. After numbing drops are placed in eye, a gel to
lubricate will also be placed in the eye. The microscope comes into close proximity to
the eye. The patient will feel the microscope against his/her eyelashes while looking
at a red light. Three scans providing a clear view of the sub-epithelial corneal nerve
layer will be performed on each patient.
Sensory and Autonomic Evaluation:
Patients seen in the Chronic Pain and Fatigue Research Center at Dominos Farms will be
evaluated by several modalities for measures of altered sensory processing and autonomic
dysfunction:
- Questionnaires of demographic and disease status information will be collected using a
general form that includes age, sex, race, marital status, education level, ethnicity,
chronicity of pain, believed cause of pain, and events associated with the onset of
pain. Participants will also complete a battery of self-report questionnaires that
characterize their functional status, pain and fatigue symptoms, cognitive
difficulties, affective status, pain beliefs, perceived stress, perceived social
support, coping strategies, sleep quality, and history of abuse. The questionnaire
battery takes approximately 1 hour to complete.
- Pressure pain sensitivity is assessed at the thumbnail using a hydraulic device that
consists of a plastic housing and piston driving a hard rubber 1 cm2 probe. After
positioning the device on the left thumb, subjects will receive an ascending series of
discrete 3 second-duration pressure stimuli beginning at 0.5 kg and increasing in 0.5
kg steps to a maximum of 10 kg (or subjective maximum less than 10 kg). Subjects will
rate the intensity of the evoked sensations using the sensory intensity Box scale, a
combined analog descriptor scale that superimposes verbal descriptors, spaced according
to ratio-scale values, on a 0-20 graphical numerical category scale.22,23 The pain
testing session lasts about 45 minutes.
- Tender point assessment: a standard means of confirming the diagnosis of fibromyalgia.
During this assessment, the examiner will use their thumb to apply minimal pressure on
pre-designated body points (such as the base of the neck, or back of the arm) and ask
if the patient is sensitive or 'tender' at these various points. Most individuals do
not describe this assessment as painful.
- Auditory sensitivity testing involves a hearing screening performed according to the
American Speech-Language-Hearing Association guidelines.24 This includes a brief case
history, otoscopic inspection, and a 25 dB HL pure-tone screen at 1000, 2000 and 4000
Hz and 35 dB HL at 500 Hz. This testing is to assure that there are no hearing
abnormalities that would cause abnormalities on the research test of interest, the
Judgment of Loudness Discomfort Levels (LDLs). This testing is performed using pure
tone acoustic stimuli at an octave frequency of 2000 Hz and signal range from 40 to 100
dB. The patient is instructed to indicate a rating of discomfort for each volume at
which the acoustic signal is presented. This test will be performed in both ascending
step-wise and random order patterns, and takes approximately 45 minutes. Each patient
will also complete a hyperacusis questionnaire,25 through which they will indicate
their experiences of real-life auditory sensitivity.
- Dysautonomia will be assessed centrally by monitoring variations in heart rate. Heart
rate variability information is obtained by use of a Holter monitor. Individuals will
remain supine for the first 5 minutes of the examination. For the remaining time period
(total: approximately 60 minutes), the Holter monitor will record a continuous
electrocardiogram (ECG) of the heart's electrical activity in response to varying but
standardized study related tasks such as questionnaire completion, discussions with
study personnel, and listening to instructions. Frequency domain analysis using fast
Fourier transformations yields information about the amount of the variance (power) in
the heart's rhythm explained by periodic oscillations of the heart rate at various
bands, including the high, low, and very low frequencies.26 Fluctuations over time in
the interval between normal heartbeats is recorded and quantified by analysis of
variability between beats.
