NCT04222660

Corneal Nerves Function and Structure

Completed NA Results posted Last updated 23 May 2025

What this trial tests

NA trial testing Blackmores Omega Daily (4 1g capsules per day) in Diabetic Peripheral Neuropathy in 44 participants. Completed in 13 May 2025.

Timeline

21 June 2021

Primary endpoint
5 June 2023

13 May 2025

Quick facts

Lead sponsor	VA Office of Research and Development
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	44
Start date	21 June 2021
Primary completion	5 June 2023
Estimated completion	13 May 2025
Sites	1 location across United States

Drugs / interventions tested

• Blackmores Omega Daily (4 1g capsules per day)

Conditions studied

• Diabetic Peripheral Neuropathy — all drugs for Diabetic Peripheral Neuropathy →

Sponsor

VA Office of Research and Development — full company profile →

Who can join

Adults 50 to 75, any sex, with Diabetic Peripheral Neuropathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cornea Sensitivity Primary · 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.

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.

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	0.177	± 0.073
Normal Subjects, Aged Match With no Symptoms of Diabetes	0.293	± 0.036

Change in Corneal Sensation Threshold Using Cochet Bonnet Filament Secondary · 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.

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	5.683	± 0.066
Normal Subjects, Aged Match With no Symptoms of Diabetes	5.953	± 0.026

Michigan Neuropathy Screening Instrument Secondary · 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.

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	5.720	± 0.0505
Normal Subjects, Aged Match With no Symptoms of Diabetes	0.5455	± 0.3123

Sensitivity to 10 g Monofilament Test Secondary · 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 va

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	0.5577	± 0.07507
Normal Subjects, Aged Match With no Symptoms of Diabetes	0.000	± 0.000

Presence of Vibratory Sensation of the Great Toe Secondary · 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 evi

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	0.6731	± 0.0551
Normal Subjects, Aged Match With no Symptoms of Diabetes	0.000	± 0.000

Presence of Reflex Secondary · 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.

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	0.8125	± 0.07855
Normal Subjects, Aged Match With no Symptoms of Diabetes	0.000	± 0.000

Visual Acuity Secondary · 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 i

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	25	± 0.001
Normal Subjects, Aged Match With no Symptoms of Diabetes	20	± 0.000

Questionnaires for Corneal Sensitivity Secondary · 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.

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	11.36	± 1.96
Normal Subjects, Aged Match With no Symptoms of Diabetes	1.09	± 0.78

Determination of Tibial Nerve Conduction Velocity Secondary · 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

Group	Value	95% CI
Type 2 Diabetes With Neuropathy	35.60	± 4.19
Normal Subjects, Aged Match With no Symptoms of Diabetes	50.50	± 3.68

Sponsor's own description

Peripheral neuropathy affects about 50% of the diabetic population and there is no treatment other than good blood glucose control, which is ineffective in subjects with type 2 diabetes. Part of the problem for the lack of an effective treatment is the inability to detect peripheral neuropathy in its early stage. The hypotheses to be addressed in the first phase of this study is that changes in cornea sensitivity (blinking and squinting) following addition of a hyperosmotic solution will provide a novel screening tool for early diagnosis of peripheral neuropathy. For the second phase of the study the investigators will examine the effect of fish oil treatment of diabetic subjects with neuropathy on corneal nerve density and sensitivity. Corneal nerves are the most highly innervated part of the human body with great sensitivity. The first phase will use this property and determine whether sensitivity is lost in diabetic patients with neuropathy. Preclinical studies have supported this hypothesis and now this will be tested in human subjects. Preclinical studies have also shown that treating diabetic rodents with fish oil improves nerve regeneration and outcome measures of peripheral in diabetic rodents. In the second phase the investigators will perform preliminary studies in human subjects with diabetic neuropathy and determine whether treating them with fish oil increases corneal nerve density and sensitivity.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent updates in the treatment of diabetic polyneuropathy.
   Fan Q, Gordon Smith A. · · 2022 · cited 8× · PMID 36311537 · DOI 10.12703/r/11-30
2. Laser Speckle Flowgraphy Reveals Widespread Reductions in Ocular Blood Flow in nonexudative Age-Related Macular Degeneration.
   Linton EF, Ahmad NU, Filister R, Wang JK, et al · · 2025 · cited 4× · PMID 39892803 · DOI 10.1016/j.ajo.2025.01.012