Corneal Confocal Microscopy in Patients With Type 1 Diabetes (CCM)

Assessing the use of corneal confocal microscopy to evaluate for early neuropathy changes in subjects with Type 1 Diabetes.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Neuropathies
• Intervention / Treatment: Device: Corneal confocal microscopy; Procedure: Skin biopsy; Procedure: Nerve conduction study; Other: Blood draw

Detailed Description

Rationale: Poorly controlled diabetes mellitus is associated with microvascular complications, which includes peripheral neuropathy. Peripheral neuropathy associated with diabetes is a painful condition. Its diagnosis is hampered by painful and long nerve conduction studies which fail to diagnose small nerve neuropathy. It is important to study methods of noninvasive methods of early detection, which are sensitive and specific in diagnosing early neuropathy and we propose a novel study that this can be detected in the cornea of the eye.

Aims:

• Estimate corneal small nerve fiber damage in young T1DM subjects (corneal fiber density, nerve branch density, and fiber length) and compare the results to healthy controls using corneal confocal microscopy (CCM).
• Estimate corneal nerve fiber damage in subjects with diabetes, with peripheral neuropathy and subjects with diabetes without peripheral neuropathy, diagnosed by skin biopsies and nerve conduction studies
• Obtain much needed normative values for CCM in adolescents and intraepidermal nerve fiber density from skin biopsies in subjects with type 1 diabetes.
• As a secondary outcome measure, to compare serum biomarkers including leptin, TNF alpha, and fibrinogen in patients with diabetes in those with neuropathy Vs. without neuropathy.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion:

• Subjects with diabetes:
• 18-30 years (cohort 1), adolescents ages 13-17 years (cohort 2).
• Type 1 Diabetes diagnosed via standard ADA criteria

Matched Controls:

• Match for age and gender
• Hemoglobin A1c <6.5%

Exclusion:

For all subjects:

• Contact lens wearers
• Diseases that could damage the cornea, other than diabetes.
• Neurologic disease
• Psychiatric disease
• Amputation
• Foot ulcers
• Pain not of neuropathic origin.
• Presence of Lupus, Sjogren's syndrome and Celiac disease
• Hyperlipidemia requiring lipid-lowering medications
• Peripheral vascular disease
• Neuropathy due to anything besides diabetes
• Presence of any medical condition that may affect nerve conduction (e.g., radiculopathy).

For healthy controls

• Family history of Type 1 Diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Type 1 Diabetes; Subjects with known Type 1 diabetes	Device: Corneal confocal microscopy; Confocal miscroscopy will be used to assess corneal nerve changes due to hyperglycemia.; Procedure: Skin biopsy; Skin biopsy will be used to assess the appearance of nerve fibers in subjects with type 1 diabetes.; Procedure: Nerve conduction study; Nerve conduction studies will be use to assess for neuropathy.; Other: Blood draw; Subjects will undergo a one time blood draw for biomarkers.
Placebo Comparator: Healthy Controls; Healthy controls	Device: Corneal confocal microscopy; Confocal miscroscopy will be used to assess corneal nerve changes due to hyperglycemia.; Procedure: Nerve conduction study; Nerve conduction studies will be use to assess for neuropathy.; Other: Blood draw; Subjects will undergo a one time blood draw for biomarkers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal small nerve fiber damage	Estimate corneal small nerve fiber damage in young T1DM subjects and compare the results to healthy controls using corneal confocal microscopy (CCM). This will be done by examining the cornea via confocal microscopy and obtaining images. These images will be evaluated looking at how many nerves there are, how they branch, and how long they are).	Assessed one time per subject during study (study completed over 3 years)
Normative values for corneal confocal microscopy (CCM)	Obtain much needed normative values for CCM in adolescents and intraepidermal nerve fiber density from skin biopsies in subjects with type 1 diabetes. This will be done by obtaining a small biopsy of skin and looking at the number of nerve fibers in the outer layer of the skin.	Assessed one time per subject during study (study completed over 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum biomarkers - leptin	Measuring serum biomarkers (blood levels) leptin. In participants with diabetes, comparing the blood level measurements of those with neuropathy vs. those without neuropathy.	Assessed one time per subject during study (study completed over 3 years)
Serum biomarkers - TNF Alpha	Measuring serum biomarkers (blood levels) Tumor Necrosis Factor (TNF) Alpha. In participants with diabetes, comparing the blood level measurements of those with neuropathy vs. those without neuropathy.	Assessed one time per subject during study (study completed over 3 years)
Serum biomarkers - fibrinogen	Measuring serum biomarkers (blood levels) fibrinogen. In participants with diabetes, comparing the blood level measurements of those with neuropathy vs. those without neuropathy.	Assessed one time per subject during study (study completed over 3 years)

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Investigators: Principal Investigator: Lisa Underland, MD, Montefiore Medical Center at Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2018
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: February 3, 2017
• First Posted (Estimate): February 7, 2017

Study Record Updates

• Last Update Posted (Actual): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetic Neuropathies
• Other Study ID Numbers: 2016-6962

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No