Trial Outcomes & Findings for Corneal Nerves Function and Structure (NCT NCT04222660)

Last Updated: 2025-05-23

Results Overview

Cornea sensitivity to a isotonic and hyperosmotic solution is evaluated as the amount of time the eyelid is closed over a period of 150 seconds following application of first isotonic saline (0.9% NaCl) followed by Muro 128 (5% NaCl solution) after a 5 minute recovery/washout period. The evaluation is done from analyzing the recordings of each event using a multi-camera video platform. The results are reported for response to saline (baseline) and Muro (stimulant) solutions as a ratio of the time the eyelids are closed vs. open over the 150 second period of the recording.

Recruitment status

COMPLETED

Study phase

Target enrollment

44 participants

Primary outcome timeframe

Examination of the response to saline and Muro 128 is preformed once in each patient immediately following their consent or if they request at a later more convenient time.

Results posted on

2025-05-23

Participant Flow

The reviewer is correct. Due to the pandemic the course of this study was dramatically changed. Initially there was going to be 2 separate protocols the first to measure cornea sensitivity using a hyperosmotic solution in 3 groups control, and diabetes with or without neuropathy. The second protocol was to be treatment with fish oil to determine whether improvement occurs. Because of COVID we were able to complete only protocol 1 and it was done in only control and diabetes neuropathy subjects.

Participant milestones

Participant milestones
Measure	Type 2 Diabetes With Neuropathy Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Overall Study STARTED	28	16
Overall Study COMPLETED	28	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Corneal Nerves Function and Structure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation.	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants	2 Participants n=7 Participants	17 Participants n=5 Participants
Age, Continuous	66.8 years STANDARD_DEVIATION 1.9 • n=5 Participants	49.8 years STANDARD_DEVIATION 5.0 • n=7 Participants	56.2 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	11 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	15 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	15 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	28 Participants n=5 Participants	16 Participants n=7 Participants	44 Participants n=5 Participants
cornea sensitivity using isotonic solution	0.089 time ratio eyelids closed vs. open STANDARD_DEVIATION 0.012 • n=5 Participants	0.085 time ratio eyelids closed vs. open STANDARD_DEVIATION 0.027 • n=7 Participants	0.088 time ratio eyelids closed vs. open STANDARD_DEVIATION 0.010 • n=5 Participants
cornea sensitivity using Cochet-Bonnet	5.68 cm STANDARD_DEVIATION 0.47 • n=5 Participants	5.95 cm STANDARD_DEVIATION 0.14 • n=7 Participants	5.78 cm STANDARD_DEVIATION 0.41 • n=5 Participants
nerve conduction	35.6 m/s STANDARD_DEVIATION 13.2 • n=5 Participants	50.5 m/s STANDARD_DEVIATION 10.4 • n=7 Participants	41.0 m/s STANDARD_DEVIATION 13.4 • n=5 Participants
nerve amplitude	3.80 uV STANDARD_DEVIATION 1.39 • n=5 Participants	14.63 uV STANDARD_DEVIATION 6.86 • n=7 Participants	7.74 uV STANDARD_DEVIATION 6.98 • n=5 Participants
Dry eye (DEQ 5) questionnaire	7.12 units on a scale STANDARD_DEVIATION 5.30 • n=5 Participants	2.00 units on a scale STANDARD_DEVIATION 3.31 • n=7 Participants	5.26 units on a scale STANDARD_DEVIATION 5.31 • n=5 Participants
Ocular Surface Disease Index (OSDI) questionnaire	11.36 units on a scale STANDARD_DEVIATION 9.80 • n=5 Participants	1.09 units on a scale STANDARD_DEVIATION 2.59 • n=7 Participants	7.63 units on a scale STANDARD_DEVIATION 9.20 • n=5 Participants
Michigan neuropathy screening instrument	5.72 units on a scale STANDARD_DEVIATION 2.52 • n=5 Participants	0.54 units on a scale STANDARD_DEVIATION 1.03 • n=7 Participants	3.84 units on a scale STANDARD_DEVIATION 3.68 • n=5 Participants

PRIMARY outcome

Timeframe: Examination of the response to saline and Muro 128 is preformed once in each patient immediately following their consent or if they request at a later more convenient time.

Population: primary outcome

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Cornea Sensitivity	0.177 time ratio of eyelids closed vs. open Standard Deviation 0.073	0.293 time ratio of eyelids closed vs. open Standard Deviation 0.036

SECONDARY outcome

Timeframe: Done once to determine whether there is a difference between control and diabetes subjects with peripheral neuropathy

This test records the mechanical sensitivity of the cornea to a filament that is touched to the cornea. The rigidity of the filament can be adjusted and the outcome is the length of the filament (6 to 1 cm) when the subjects blinks. The data will be recorded as cm.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Change in Corneal Sensation Threshold Using Cochet Bonnet Filament	5.683 cm Standard Error 0.066	5.953 cm Standard Error 0.026

SECONDARY outcome

Timeframe: Done once as part of the determination to the subjects peripheral neuropathy.

All subjects will answer a 15 question survey that relates to symptoms of peripheral neuropathy. The score range is 0-13 with the higher score indicating poorer outcome or increased peripheral neuropathy.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Michigan Neuropathy Screening Instrument	5.720 units on a scale Standard Error 0.0505	0.5455 units on a scale Standard Error 0.3123

SECONDARY outcome

Timeframe: Done once as a determination of the presence of peripheral neuropathy

The 10 g monofilament test is a routine evaluation used to screen the diabetic foot for loss of sensory sensation and part of the standard of care for any diabetic patient. The subject will remove their footwear and lie down on a table. The filament will be applied perpendicular to the skin surface on the bottom of the feet will sufficient force to allow the filament to bend. This is repeated 5 times. Each subject will be asked to tell the examiner if they feel it. The scale is 0 to 1. If the subject feels the monofilament the value each time the score given is 0. If there is no feeling the value is 1. For reduced sensitivity, for example feels the monofilament 2 or 3 times during the test the score is 0.5. A higher score is evidence of peripheral neuropathy.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Sensitivity to 10 g Monofilament Test	0.5577 units on a scale Standard Error 0.07507	0.000 units on a scale Standard Error 0.000

SECONDARY outcome

Timeframe: Done once as a determination of the presence of peripheral neuropathy

Vibratory sensation is a standard of care test used with patients with diabetes to test sensory nerve sensation. A 128 Hz tuning fork is used and placed over the dorsum of the great toe on the boney prominence of the distal interphalangeal joint. The subject is asked to tell the examiner if they feel the object touching their toe. This is repeated 3 times. The scale is 0 to 1. If the subject feels the object the score given is 0. If the subject fails to feel the object all 3 times the score is 1. If they feel it once or twice during the examination the score given is 0.5. A higher score is evidence of peripheral neuropathy.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Presence of Vibratory Sensation of the Great Toe	0.6731 units on a scale Standard Error 0.0551	0.000 units on a scale Standard Error 0.000

SECONDARY outcome

Timeframe: Done once as a determination of the presence of peripheral neuropathy

Reflex testing is commonly used to detect sensory neuropathy in diabetic patients. The ankle reflex is examined by aligning the subjects ankle into a neutral position and the examiner strikes the Achilles tendon with a neurological hammer. An abnormal result is recorded if the subject does not display any ankle plantarflexion. The scale is 0 to 1. If the reflex is present the score given is 0. If no reflex is present the score given is 1. If the response is reduced the score given is 0.5. A higher score is evidence of peripheral neuropathy.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Presence of Reflex	0.8125 units on a scale Standard Error 0.07855	0.000 units on a scale Standard Error 0.000

SECONDARY outcome

Timeframe: Done once to determine the subjects visual ability

A routine visual acuity eye examination will be performed. Subjects vision will be measured by having the subject read the smallest letters on an eye chart with their glasses or best correction. Visual acuity (VA) is a measure of the ability of the eye to distinguish shapes and the details of objects at a given distance (20 feet). A person with "normal vision" scores 20/20 as did all our controls. A person with 20/40 vision sees things at 20 feet that most people who don't need vision correction can see at 40 feet. Our subjects with diabetic neuropathy mean score was 20/25. The first number in the score is the number of feet for the test and this is commonly 20 feet. The second number is their visualization of the letters on the eye chart. The investigators used the mean of the second number for analysis. This takes about 5 minutes or less.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Visual Acuity	25 units on a scale Standard Error 0.001	20 units on a scale Standard Error 0.000

SECONDARY outcome

Timeframe: Done once to determine extent of common eye disease such as dry eye

Ocular Surface Disease Index (OSDI contains 12 questions relating to eye sensitivity to light, vision acuity, dryness, sensitivity when reading, using the computer, and watching TV). The OSDI is assessed on a scale of 0 to 100, with higher scores representing greater disability.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Questionnaires for Corneal Sensitivity	11.36 units on a scale Standard Error 1.96	1.09 units on a scale Standard Error 0.78

SECONDARY outcome

Timeframe: Done once as a determination of the presence of peripheral neuropathy

This is a non-invasive method of determining conduction velocity of the tibial nerve. the scale is meters per second or m/s. The subject will be instructed to lie down on a examination table with shoes and socks removed. Afterwards, the lower ankle will be swabbed with an alcohol patch and allowed to air dry. A device containing 2 posts (about 3 inches apart) will be placed on the lower ankle in the region of the Achilles and activated. For a period of 5-10 sec the device sends a pulse stimulating the nerve distally (post located at the lower part of the ankle) and the response recorded by the post located distally on the skin of the upper part of the ankle. The nerve conduction is recorded electronically by the device and data down loaded to a secured computer. During the time of the analyses the subject will feel dual pulsating sensation that will last up to 10 sec.

Outcome measures

Outcome measures
Measure	Type 2 Diabetes With Neuropathy n=28 Participants Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.	Normal Subjects, Aged Match With no Symptoms of Diabetes n=16 Participants Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation. Blackmores Omega Daily (4 1g capsules per day): Subjects enrolled in phase two of the study will be instructed to take 4 capsules per day (2 in the morning and 2 in the evening). Each capsule contains 1000 mg of triglyceride; 35% eicosapentaenoic acid and 25% docosahexaenoic acid.
Determination of Tibial Nerve Conduction Velocity	35.60 m/s Standard Error 4.19	50.50 m/s Standard Error 3.68

Adverse Events

Type 2 Diabetes With Neuropathy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Normal Subjects, Aged Match With no Symptoms of Diabetes

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Mark Yorek

Iowa City VA Healthcare System

Phone: 13193380581

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place