Corneal Confocal Microscopy to Detect Diabetic Neuropathy in Children (CCM)

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes; Neuropathy; Retinopathy
• Intervention / Treatment: 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

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

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 diabetic neuropathy 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 diabetic neuropathy in our pediatric population.

• Study Type: Observational
• Enrollment (Actual): 176

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2M 1V5
      • Alberta Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cases: Children seen at the Alberta Children's Hospital Diabetes Clinic in Calgary Controls: 8-18 year old healthy children

Description

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.

Exclusion Criteria:

• Patients with known history of corneal abnormality, trauma, or surgery
• Any other cause of neuropathy
• Individuals with uncontrolled hypothyroidism
• Individuals with celiac disease
• Other serious chronic illnesses besides diabetes
• Inability to cooperate with testing
• Families unwilling to provide written informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The utility of corneal confocal microscopy to assess diabetic neuropathy in children.	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal nerve density (CND) by CCM	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	Single time point
Changes in corneal nerve morphology two years after the initial CCM exam.	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.	2 years
Corneal nerve length (CNL) by CCM.	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	Single time point
Corneal nerve branching density (CBD) by CCM	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	Single time point

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Danièle Pacaud, Md, FRCPC, University of Calgary

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: June 17, 2013
• First Submitted That Met QC Criteria: December 16, 2014
• First Posted (Estimate): December 22, 2014

Study Record Updates

• Last Update Posted (Actual): October 3, 2019
• Last Update Submitted That Met QC Criteria: October 1, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes; Detection; Cornea; Neuropathy; Confocal microscopy
• 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: E-21944