CCM: Corneal Confocal Microscopy to Detect Diabetic Neuropathy in Children

Sponsor

University of Calgary (Other)

Overall Status

Completed

CT.gov ID

NCT02321904

Collaborator

Juvenile Diabetes Research Foundation (Other)

176

Enrollment

Location

134

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall aim of this study is to confirm the utility of corneal confocal microscopy (CCM) as a new technique to rapidly and non-invasively assess diabetic neuropathy (DN) in children. This study will be divided into two phases: Phase 1 will be a cross-sectional study of children with type 1 diabetes and normal controls, while phase 2 will be a longitudinal assessment of a subgroup of children with type 1 diabetes recruited during Phase 1.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Neuropathy Retinopathy	Procedure: Corneal Confocal Microscopy Procedure: Nerve Conduction Studies Procedure: Quantitative sensory testing Procedure: Neuropathy Symptom Score Procedure: Clinical nerve examination

Detailed Description

In phase 1: To compare corneal nerve density (CND), length (CNL), and branching (CBD) by CCM between

children with type 1 diabetes for 5 years or more to children without diabetes;
children with type 1 diabetes with and without evidence of diabetic neuropathy;
to examine the relationship between CND, CNL & CBD and known risk factors of diabetic neuropathy

In phase 2:

to examine for changes in corneal nerve morphology two years after the initial CCM exam.
to describe the evolution of diabetic neuropathy based on clinical symptoms, neurological deficits, and other tests of nerve dysfunction.
to assess if changes in corneal nerve morphology correlate with changes in nerve conduction velocity and autonomic testing.
To examine the risk factors associated with progression of diabetic neuropathy in our pediatric population.

Study Design

Study Type:

Observational

Actual Enrollment :

176 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Corneal Confocal Microscopy to Detect Diabetic Neuropathy in Children

Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Diabetic cases Children with Type 1 Diabetes 8 to 18 years old followed at the Alberta Children's Hospital Diabetes Clinic with duration of diabetes for at least 5 years will undergo Corneal Confocal Microscopy, Nerve Conduction Studies, Quantitative sensory testing, Neuropathy Symptom Scoring and Clinical nerve examinations.	Procedure: Corneal Confocal Microscopy Close-up pictures of the front part of the eye (the cornea) Procedure: Nerve Conduction Studies The following assessments will be made: a) amplitude of nerve action potential (μV) and conduction velocity (m/s) of the sural sensory nerve by antidromic stimulation; b) motor nerve conduction velocity (m/s), maximum M-wave amplitude (mV) and motor nerve distal latency (ms) of the peroneal motor nerve; and c) tibial nerve conduction study will also be obtained if tolerated. Procedure: Quantitative sensory testing Standardized vibratory and thermal stimulation levels applied to the subject's non-dominant big toe. Procedure: Neuropathy Symptom Score A list of 18 motor, sensory and autonomic symptoms encountered in a diabetic patients with neuropathy obtained by interview. Procedure: Clinical nerve examination Summated score of the lower extremities. Neurological examination assessing muscle strength, knee and ankle reflexes, sensation in the great toes will be evaluated for light touch-pressure, temperature, pin-prick, vibratory sense and joint position sense.
Normal controls Healthy children aged 8 to 18 years will undergo Corneal Confocal Microscopy, Nerve Conduction Studies, Quantitative sensory testing, Neuropathy Symptom Scoring and Clinical nerve examinations.	Procedure: Corneal Confocal Microscopy Close-up pictures of the front part of the eye (the cornea) Procedure: Nerve Conduction Studies The following assessments will be made: a) amplitude of nerve action potential (μV) and conduction velocity (m/s) of the sural sensory nerve by antidromic stimulation; b) motor nerve conduction velocity (m/s), maximum M-wave amplitude (mV) and motor nerve distal latency (ms) of the peroneal motor nerve; and c) tibial nerve conduction study will also be obtained if tolerated. Procedure: Quantitative sensory testing Standardized vibratory and thermal stimulation levels applied to the subject's non-dominant big toe. Procedure: Neuropathy Symptom Score A list of 18 motor, sensory and autonomic symptoms encountered in a diabetic patients with neuropathy obtained by interview. Procedure: Clinical nerve examination Summated score of the lower extremities. Neurological examination assessing muscle strength, knee and ankle reflexes, sensation in the great toes will be evaluated for light touch-pressure, temperature, pin-prick, vibratory sense and joint position sense.

Arm

Intervention/Treatment

Diabetic cases

Children with Type 1 Diabetes 8 to 18 years old followed at the Alberta Children's Hospital Diabetes Clinic with duration of diabetes for at least 5 years will undergo Corneal Confocal Microscopy, Nerve Conduction Studies, Quantitative sensory testing, Neuropathy Symptom Scoring and Clinical nerve examinations.

Procedure: Corneal Confocal Microscopy

Close-up pictures of the front part of the eye (the cornea)

Procedure: Nerve Conduction Studies

The following assessments will be made: a) amplitude of nerve action potential (μV) and conduction velocity (m/s) of the sural sensory nerve by antidromic stimulation; b) motor nerve conduction velocity (m/s), maximum M-wave amplitude (mV) and motor nerve distal latency (ms) of the peroneal motor nerve; and c) tibial nerve conduction study will also be obtained if tolerated.

Procedure: Quantitative sensory testing

Standardized vibratory and thermal stimulation levels applied to the subject's non-dominant big toe.

Procedure: Neuropathy Symptom Score

A list of 18 motor, sensory and autonomic symptoms encountered in a diabetic patients with neuropathy obtained by interview.

Procedure: Clinical nerve examination

Summated score of the lower extremities. Neurological examination assessing muscle strength, knee and ankle reflexes, sensation in the great toes will be evaluated for light touch-pressure, temperature, pin-prick, vibratory sense and joint position sense.

Normal controls

Healthy children aged 8 to 18 years will undergo Corneal Confocal Microscopy, Nerve Conduction Studies, Quantitative sensory testing, Neuropathy Symptom Scoring and Clinical nerve examinations.

Procedure: Corneal Confocal Microscopy

Close-up pictures of the front part of the eye (the cornea)

Procedure: Nerve Conduction Studies

Procedure: Quantitative sensory testing

Standardized vibratory and thermal stimulation levels applied to the subject's non-dominant big toe.

Procedure: Neuropathy Symptom Score

A list of 18 motor, sensory and autonomic symptoms encountered in a diabetic patients with neuropathy obtained by interview.

Procedure: Clinical nerve examination

Outcome Measures

Primary Outcome Measures

The utility of corneal confocal microscopy to assess diabetic neuropathy in children. [2 years]
To confirm the utility of corneal confocal microscopy (CCM) as a new technique to rapidly assess diabetic neuropathy (DN) in children. This non-invasive eye imaging method may be a superior alternative to traditional nerve conduction studies. This study will be divided into two phases: Phase 1 will be a cross-sectional study of children with Type 1 Diabetes (T1D) and normal controls, while phase 2 will be a longitudinal assessment of a subgroup of T1D children recruited during Phase 1.

Secondary Outcome Measures

Corneal nerve density (CND) by CCM [Single time point]
To compare corneal nerve density (CND) between children with T1D for 5 years or more to children without diabetes; children with T1D with and without evidence of DN; to examine the relationship between CND, CNL & CBD and known risk factors of DN
Changes in corneal nerve morphology two years after the initial CCM exam. [2 years]
In phase 2 : 1) to examine for changes in corneal nerve morphology two years after the initial CCM exam. 2) to describe the evolution of DN in based on clinical symptoms, neurological deficits, and other tests of nerve dysfunction. 3) to assess if changes in corneal nerve morphology correlate with changes in nerve conduction velocity and autonomic testing. 4) To examine the risk factors associated with progression of DN in our pediatric population.
Corneal nerve length (CNL) by CCM. [Single time point]
To compare corneal nerve length (CNL), by CCM between children with T1D for 5 years or more to children without diabetes; children with T1D with and without evidence of DN; to examine the relationship between CND, CNL & CBD and known risk factors of DN
Corneal nerve branching density (CBD) by CCM [Single time point]
To compare corneal nerve branching density (CBD) by CCM between children with T1D for 5 years or more to children without diabetes; children with T1D with and without evidence of DN; to examine the relationship between CND, CNL & CBD and known risk factors of DN

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

CASES: Children with Type 1 Diabetes 8 to 18 years old followed at the Alberta Children's Hospital Diabetes Clinic with a duration of diabetes of at least 5 years.
CONTROLS: Healthy children aged 8 to 18 years.