Corneal Nerves Function and Structure

NCT04222660 | Completed Results

• 3 other identifiers: C0889-RRX000889-065R01DK107399-04
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetic Peripheral Neuropathy

Keywords

diabetes; neuropathy; fish oil; cornea; omega 3 polyunsaturated fatty acids

Outcome Measures

Primary Outcomes (1)

• Cornea Sensitivity

  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.

  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.

Secondary Outcomes (8)

• Change in Corneal Sensation Threshold Using Cochet Bonnet Filament

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

• Michigan Neuropathy Screening Instrument

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

• Sensitivity to 10 g Monofilament Test

  Done once as a determination of the presence of peripheral neuropathy

• Presence of Vibratory Sensation of the Great Toe

  Done once as a determination of the presence of peripheral neuropathy

• Presence of Reflex

  Done once as a determination of the presence of peripheral neuropathy

Study Arms (3)

Type 2 diabetes without neuropathy

EXPERIMENTAL

Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation.

Dietary Supplement: Blackmores Omega Daily (4 1g capsules per day)

Type 2 diabetes with neuropathy

EXPERIMENTAL

Subjects with type 2 diabetes will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation.

Dietary Supplement: Blackmores Omega Daily (4 1g capsules per day)

Normal subjects, aged match with no symptoms of diabetes

EXPERIMENTAL

Healthy, aged matched control subjects will be enrolled and determination if they have neuropathy will be determined from their clinical record and evaluation.

Dietary Supplement: Blackmores Omega Daily (4 1g capsules per day)

Interventions

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

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.

Also known as: fish oil

Normal subjects, aged match with no symptoms of diabetes; Type 2 diabetes with neuropathy; Type 2 diabetes without neuropathy

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes patients diagnosed based on the opinion of an Endocrinologist (Dr. Correia), the absence of a history of ketoacidosis, and a C-peptide \> 0.8 ng/ml
• At least 5 year known duration of diabetes.
• HbA1c \< 9.0%
• None or mild to moderate peripheral neuropathy based on medical record, Michigan Neuropathy Screening Instrument including response to monofilament test, ankle reflex test, vibration perception threshold examination using a 128 Hz tuning fork as well as hot and cold sensation evaluation

You may not qualify if:

• Any neurologic, muscular, genetic, or other condition known to affect nerve or muscle function
• Electrolyte abnormalities, untreated hypothyroidism, abnormalities in calcium, phosphate, or magnesium concentrations, or any other metabolic disturbance affecting neural function
• Cigarette smoking in the past year
• Peripheral vascular, cardiac, pulmonary, or any other disorder affecting blood or tissue oxygenation
• Risk of bleeding disorder or on medication known to increase risk of bleeding
• History for use of aspirin
• Any other medical or psychological condition judged to limit compliance with the protocol or interpretation of results
• History of diabetic foot ulcer
• LDL \> 100 mg/100ml, HDL \< 30 mg/100ml, Triglyceride \> 400 mg/100ml.\* 10) BP \< 140 systolic and 80 diastolic
• BMI 45
• Insulin use to manage diabetes 200 units
• History of taking fish oil supplements
• The investigators are limiting subject population to those over 50 thus pregnancy should not be an issue nonetheless females who are pregnant, looking to become pregnant or are breast feeding will be excluded (\* After overnight fast of 8-12 h; Average of three determinations in the sitting position after at least 5 minutes rest.)

Sponsors & Collaborators

• VA Office of Research and Development: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Iowa City VA Health Care System, Iowa City, IA

Iowa City, Iowa, 52246-2292, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus; Corneal Diseases

Interventions

Fish Oils

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Oils; Lipids

Limitations and Caveats

Study weaknesses include the number of subjects enrolled being primarily male. The control group was not well age matched. Recruitment of diabetes subjects was restricted to those with known peripheral neuropathy. Additional studies are needed that include diabetes subjects without peripheral neuropathy and those with mild peripheral neuropathy.

Results Point of Contact

• Title: Dr. Mark Yorek
• Organization: Iowa City VA Healthcare System

mark.yorek@va.gov

13193380581

Study Officials

• Mark A Yorek, PhD

  Iowa City VA Health Care System, Iowa City, IA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: The study will be done in two phases. In the second phase the investigators will investigate whether increased intake of fish oil improves diabetic peripheral neuropathy including improvement in corneal nerve morphology and sensitivity. Subjects will receive 4g (2g twice a day) of fish oil per day in capsule form. The second phase of the study will be done in 2 of the 3 groups. The two groups for this phase of the study will be the control subjects and the diabetic subjects with neuropathy.

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: January 10, 2020
• Study Start: June 21, 2021
• Primary Completion: June 5, 2023
• Study Completion: May 13, 2025
• Last Updated: May 23, 2025
• Results First Posted: July 3, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)