Diabetic PolyneuropathyNCT02423434
Evaluation of Corneal Confocal Microscopy for the Identification and Prediction of Neuropathy in Type 1 Diabetes
An observational study of Diabetic Polyneuropathy and Diabetes Mellitus, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 5 sites in 4 countries.
Trial summary
Through the multinational pooled dataset approach, this trial will aim to derive and validate specific in vivo Corneal Confocal Microscopy (CCM) parameter thresholds for the identification of diabetic polyneuropathy, and - more importantly - the identification of individuals at future risk. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Polyneuropathy, Diabetes Mellitus, Diabetes Mellitus, Type 1
- What is being tested?
- Exposure: Corneal nerve fibre morphology by the CCM Procedure
- How many people
- 624 participants
- Where
- 5 sitesin 4 countries
- Study dates
- Sep 2014to Aug 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This longitudinal observational cohort study of diagnosis involves follow-up in two study groups: A. Five- to seven-year follow-up re-examination of 5 well-characterized type 1 diabetes (T1D) cohorts (N=516) comprising a neuropathic subset and a non-neuropathic subset. B. Three- to six-year follow-up re-examination of 4 well-characterized type 2 diabetes (T2D) cohorts (N=524) each comprising a neuropathic subset and a non-neuropathic subset. T1D Subjects. The five study sites are composed of cohort studies for T1D initiated between 2008 and 2011. Together, the five sites have studied 516 subjects at baseline with T1D, 363 without DPN and 151 with DPN at baseline. T2D Subjects. Four of the sites have studied subjects with T2D. Together, the four sites have studied 524 subjects at baseline with T2D, 241 without DPN and 283 with DPN at baseline. Of the 1040 total subjects examined in baseline procedures, we anticipate follow-up of 70% for a total re-examined cohort 729.
Who may be able to join
- Individuals of any gender or race aged 18 or above
- Type 1 diabetes mellitus or type 2 diabetes mellitus as defined by the American Diabetes Association guidelines (2014) of any duration
- Availability of the initial CCM examination performed two to eight years ago
- Ability to understand and cooperate with study procedures
Who cannot join
- Confirmed to have neuropathy owing to non-diabetic causes (such as familial, alcoholic, nutritional, uremic)
- Current eye infection, corneal damage, or severe movement disorders which could preclude a safe CCM exam
- Allergy to proparacaine (the ocular topical anaesthetic used for the CCM exam)
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Canada2 sites
University of Calgary
Calgary, Alberta, T3B6A8
Mount Sinai Hospital and University Health Network
Toronto, Ontario, M5G 2C4
About this study
Official title: Multinational Collaborative Evaluation of Corneal Confocal Microscopy as a Surrogate Endpoint for the Identification and Prediction of Diabetic Neuropathy in Type 1 Diabetes
Through the multinational pooled dataset approach, this trial will aim to derive and validate specific in vivo Corneal Confocal Microscopy (CCM) parameter thresholds for the identification of diabetic polyneuropathy, and - more importantly - the identification of individuals at future risk. Results of the study will permit application in clinical practice and intervention trials for diabetic polyneuropathy (DPN) risk stratification.
The primary goal of the study is to re-examine individuals with type 1 and type 2 diabetes with and without neuropathy, who had CCM performed in the past as a part of their neurological examination, to assess concurrent and predictive validity of different CCM parameters in individuals . These subjects will be invited to the study to be re-examined by CCM along with other neurological tests (physical exam, nerve conduction studies, quantitative sensory testing, blood test and in some centres also skin biopsy) during the single study visit. Additionally CCM data will be analyzed both manually and by recently developed automated analytical software to evaluate accuracy of the automated method. Evaluation of automated image analysis will influence likelihood of successful knowledge translation of this surrogate biomarker for DPN into clinical practice - in which the procedure could be harmonized with annual retinal examinations - and into intervention trials.
Secondary aim of the study is to determine the factors associated with CCM parameters and their longitudinal change and collect bio-samples for future research in this field.
Read the detailed description
The diffuse injury to peripheral nerves (diabetic neuropathy) is exceptionally common in type 1 diabetes, but there is a lack of an objective surrogate marker to identify early subclinical stages when treatments might be most effective, prior to late-stage progression to troublesome and costly foot infection, ulceration, and limb amputation. In contrast to the ability to objectively measure disease-specific surrogate markers for retinopathy and nephropathy, this lack of a diabetic neuropathy surrogate marker has seriously impeded the development of specific interventions in clinical research trials. Representing 5 independent research groups that have together created a consortium of investigators dedicated to the development of a surrogate marker for early diabetic neuropathy, we have focused on using the eye as a window to non-invasively image by a method of in-vivo corneal confocal microscopy (CCM) the small nerve fibres that innervate the cornea. We have demonstrated that changes in these nerve fibre endings occur early in the development of neuropathy, reflect well the changes seen in other peripheral nerves by invasive skin biopsy evaluation, and that their measurement is feasible and reproducible. As a multinational consortium, we have the benefit in this proposal of pooling multiple cohorts to apply the most valid study methods in biomarker development. First, we aim to determine in the analysis of an existing pooled dataset of 516 type 1 and 524 type 2 diabetes subjects the exact levels of CCM measurement that can identify the presence of diabetic neuropathy. Secondly, we propose over three years to re-examine at least 70% of this cohort, which will provide 5- to 7-year follow-up data to determine which type and level of CCM measurement can predict the future onset of neuropathy, as well as its progression in those who had neuropathy at baseline. Finally, we will evaluate the role of time- and cost-saving automated image analysis software. By virtue of large sample size from data pooling, we are uniquely afforded the methodological power to confirm our objectives by way of separate derivation and validation analysis sets. Through a unique and unprecedented multinational pooled dataset approach for diabetic neuropathy, this work will derive and validate specific CCM parameter thresholds for the identification of neuropathy, and - more importantly - the identification of individuals at future risk. These results will permit application in clinical practice and intervention trials for neuropathy risk stratification. Evaluation of automated image analysis will influence likelihood of successful knowledge translation of this surrogate biomarker into clinical practice - in which the procedure could be harmonized with annual retinal examinations - and into intervention trials.
- Conditions
- Diabetic Polyneuropathy, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes Complications
- Being tested
- Exposure: Corneal nerve fibre morphology by the CCM Procedure
- Keywords
- Corneal Confocal Microscopy, Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetic Neuropathy, Diabetes Complications
- Medical subject headings
- Diabetic Neuropathies, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure: Corneal nerve fibre morphology by the CCM ProcedureOther
CCM is a non-invasive method for direct visualization of corneal nerve fibers. Previous research work has confirmed that corneal nerves status correlates with both small and large fibre damage as assessed by quantitative sensory testing and nerve conduction.
In the current trial subjects will undergo a bilateral examination of the Bowman's layer of the cornea using the Rostock Cornea Module of the Heidelberg Tomograph III (Heidelberg Engineering, Smithfield RI, USA) to determine their corneal nerve fiber length, corneal nerve fiber density, corneal nerve branch density, and the tortuosity coefficient. Topical anaesthetic and a viscous gel medium will be applied to the eye, which will create a visual gel bridge between the cornea and the sterile single-use cap on the microscope objective lens. After the interface between the corneal epithelium and Bowman's layer is identified, batches of images will be taken and the most technically sound images will be identified and analyzed.
| Study group | Role | What they receive |
|---|---|---|
| Corneal Confocal Microscopy subjects | Not described Receives: Other: Exposure: Corneal nerve fibre morphology by the CCM Procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the Concurrent Validity of CCM Parameters from Cross-Sectional Analysis of Well-Characterized T1D and T2D Subjects.
Measured: Any data obtained from pre-study measurements
Evaluate the Predictive Validity of CCM Parameters based on the 5-7 year Incidence of Neuropathy in Well-Characterized T1D and T2D Subjects Without Neuropathy at Baseline
Measured: Study visit
Evaluate the Predictive Validity of CCM Parameters for 5-7 year Progression of Neuropathy
Measured: Study visit
Comparison of Manual versus Automated Image analysis
Measured: Pre-study and study visit data
Secondary outcomes (1)
Determination of the Factors associated with CCM Parameters and their Longitudinal Change
Measured: Study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study startSep 2014
- Primary completionAug 2018
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (33)Papers the sponsor has linked to this study.
- Other trials for Diabetic PolyneuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 624 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Calgary, Queensland University of Technology, University of Michigan, University of Manchester
- Responsible party
- Sponsor
- Investigators
- Bruce A Perkins, MD, Principal investigator, MOUNT SINAI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423434
- Sponsor's protocol ID
- DP3DK104386
- Other IDs
- 1DP3DK104386-01
- Status last verified
- Nov 2019
- First submitted
- 17 Apr 2015
- Last updated
- 6 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tavakoli M, Ferdousi M, Petropoulos IN, Morris J, Pritchard N, Zhivov A, Ziegler D, Pacaud D, Romanchuk K, Perkins BA, Lovblom LE, Bril V, Singleton JR, Smith G, Boulton AJ, Efron N, Malik RA. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set. Diabetes Care. 2015 May;38(5):838-43. doi: 10.2337/dc14-2311. Epub 2015 Jan 29.
PubMed 25633665Pritchard N, Edwards K, Russell AW, Perkins BA, Malik RA, Efron N. Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes. Diabetes Care. 2015 Apr;38(4):671-5. doi: 10.2337/dc14-2114. Epub 2015 Jan 8.
PubMed 25573881Tavakoli M, Begum P, McLaughlin J, Malik RA. Corneal confocal microscopy for the diagnosis of diabetic autonomic neuropathy. Muscle Nerve. 2015 Sep;52(3):363-70. doi: 10.1002/mus.24553. Epub 2015 Jun 18.
PubMed 25556884Dehghani C, Pritchard N, Edwards K, Vagenas D, Russell AW, Malik RA, Efron N. Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes: development of a potential measure of diabetic peripheral neuropathy. Invest Ophthalmol Vis Sci. 2014 Nov 18;55(12):7982-90. doi: 10.1167/iovs.14-15605.
PubMed 25406279Maddaloni E, Sabatino F, Del Toro R, Crugliano S, Grande S, Lauria Pantano A, Maurizi AR, Palermo A, Bonini S, Pozzilli P, Manfrini S. In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes. Diabet Med. 2015 Feb;32(2):262-6. doi: 10.1111/dme.12583. Epub 2014 Sep 24.
PubMed 25251450Stem MS, Hussain M, Lentz SI, Raval N, Gardner TW, Pop-Busui R, Shtein RM. Differential reduction in corneal nerve fiber length in patients with type 1 or type 2 diabetes mellitus. J Diabetes Complications. 2014 Sep-Oct;28(5):658-61. doi: 10.1016/j.jdiacomp.2014.06.007. Epub 2014 Jun 17.
PubMed 25044236Asghar O, Petropoulos IN, Alam U, Jones W, Jeziorska M, Marshall A, Ponirakis G, Fadavi H, Boulton AJ, Tavakoli M, Malik RA. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014 Sep;37(9):2643-6. doi: 10.2337/dc14-0279. Epub 2014 Jun 26.
PubMed 24969581Edwards K, Pritchard N, Vagenas D, Russell A, Malik RA, Efron N. Standardizing corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy. Diabet Med. 2014 Oct;31(10):1205-9. doi: 10.1111/dme.12466. Epub 2014 May 24.
PubMed 24750318Ziegler D, Papanas N, Zhivov A, Allgeier S, Winter K, Ziegler I, Bruggemann J, Strom A, Peschel S, Kohler B, Stachs O, Guthoff RF, Roden M; German Diabetes Study (GDS) Group. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes. 2014 Jul;63(7):2454-63. doi: 10.2337/db13-1819. Epub 2014 Feb 26.
PubMed 24574045Petropoulos IN, Alam U, Fadavi H, Marshall A, Asghar O, Dabbah MA, Chen X, Graham J, Ponirakis G, Boulton AJ, Tavakoli M, Malik RA. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Invest Ophthalmol Vis Sci. 2014 Apr 3;55(4):2071-8. doi: 10.1167/iovs.13-13787.
PubMed 24569580Tavakoli M, Petropoulos IN, Malik RA. Corneal confocal microscopy to assess diabetic neuropathy: an eye on the foot. J Diabetes Sci Technol. 2013 Sep 1;7(5):1179-89. doi: 10.1177/193229681300700509.
PubMed 24124944Petropoulos IN, Alam U, Fadavi H, Asghar O, Green P, Ponirakis G, Marshall A, Boulton AJ, Tavakoli M, Malik RA. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care. 2013 Nov;36(11):3646-51. doi: 10.2337/dc13-0193. Epub 2013 Jul 22.
PubMed 23877983Papanas N, Ziegler D. Corneal confocal microscopy: a new technique for early detection of diabetic neuropathy. Curr Diab Rep. 2013 Aug;13(4):488-99. doi: 10.1007/s11892-013-0390-z.
PubMed 23666893Sivaskandarajah GA, Halpern EM, Lovblom LE, Weisman A, Orlov S, Bril V, Perkins BA. Structure-function relationship between corneal nerves and conventional small-fiber tests in type 1 diabetes. Diabetes Care. 2013 Sep;36(9):2748-55. doi: 10.2337/dc12-2075. Epub 2013 Apr 11.
PubMed 23579181Halpern EM, Lovblom LE, Orlov S, Ahmed A, Bril V, Perkins BA. The impact of common variation in the definition of diabetic sensorimotor polyneuropathy on the validity of corneal in vivo confocal microscopy in patients with type 1 diabetes: a brief report. J Diabetes Complications. 2013 May-Jun;27(3):240-2. doi: 10.1016/j.jdiacomp.2012.10.011. Epub 2012 Dec 21.
PubMed 23266297
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multinational Collaborative Evaluation of Corneal Confocal Microscopy as a Surrogate Endpoint for the Identification and Prediction of Diabetic Neuropathy in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02423434
- Acronym / sponsor ID
- DP3DK104386
- Conditions
- Diabetic Polyneuropathy, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes Complications
- Keywords
- Corneal Confocal Microscopy, Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetic Neuropathy, Diabetes Complications
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 624 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Calgary, Queensland University of Technology, University of Michigan, University of Manchester
- Study start
- Sep 2014 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 22 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Through the multinational pooled dataset approach, this trial will aim to derive and validate specific in vivo Corneal Confocal Microscopy (CCM) parameter thresholds for the identification of diabetic polyneuropathy, and - more importantly - the identification of individuals at future risk. Results of the study will permit application in clinical practice and intervention trials for diabetic polyneuropathy (DPN) risk stratification.
The primary goal of the study is to re-examine individuals with type 1 and type 2 diabetes with and without neuropathy, who had CCM performed in the past as a part of their neurological examination, to assess concurrent and predictive validity of different CCM parameters in individuals . These subjects will be invited to the study to be re-examined by CCM along with other neurological tests (physical exam, nerve conduction studies, quantitative sensory testing, blood test and in some centres also skin biopsy) during the single study visit. Additionally CCM data will be analyzed both manually and by recently developed automated analytical software to evaluate accuracy of the automated method. Evaluation of automated image analysis will influence likelihood of successful knowledge translation of this surrogate biomarker for DPN into clinical practice - in which the procedure could be harmonized with annual retinal examinations - and into intervention trials.
Secondary aim of the study is to determine the factors associated with CCM parameters and their longitudinal change and collect bio-samples for future research in this field.
Detailed description
The diffuse injury to peripheral nerves (diabetic neuropathy) is exceptionally common in type 1 diabetes, but there is a lack of an objective surrogate marker to identify early subclinical stages when treatments might be most effective, prior to late-stage progression to troublesome and costly foot infection, ulceration, and limb amputation. In contrast to the ability to objectively measure disease-specific surrogate markers for retinopathy and nephropathy, this lack of a diabetic neuropathy surrogate marker has seriously impeded the development of specific interventions in clinical research trials. Representing 5 independent research groups that have together created a consortium of investigators dedicated to the development of a surrogate marker for early diabetic neuropathy, we have focused on using the eye as a window to non-invasively image by a method of in-vivo corneal confocal microscopy (CCM) the small nerve fibres that innervate the cornea. We have demonstrated that changes in these nerve fibre endings occur early in the development of neuropathy, reflect well the changes seen in other peripheral nerves by invasive skin biopsy evaluation, and that their measurement is feasible and reproducible. As a multinational consortium, we have the benefit in this proposal of pooling multiple cohorts to apply the most valid study methods in biomarker development. First, we aim to determine in the analysis of an existing pooled dataset of 516 type 1 and 524 type 2 diabetes subjects the exact levels of CCM measurement that can identify the presence of diabetic neuropathy. Secondly, we propose over three years to re-examine at least 70% of this cohort, which will provide 5- to 7-year follow-up data to determine which type and level of CCM measurement can predict the future onset of neuropathy, as well as its progression in those who had neuropathy at baseline. Finally, we will evaluate the role of time- and cost-saving automated image analysis software. By virtue of large sample size from data pooling, we are uniquely afforded the methodological power to confirm our objectives by way of separate derivation and validation analysis sets. Through a unique and unprecedented multinational pooled dataset approach for diabetic neuropathy, this work will derive and validate specific CCM parameter thresholds for the identification of neuropathy, and - more importantly - the identification of individuals at future risk. These results will permit application in clinical practice and intervention trials for neuropathy risk stratification. Evaluation of automated image analysis will influence likelihood of successful knowledge translation of this surrogate biomarker into clinical practice - in which the procedure could be harmonized with annual retinal examinations - and into intervention trials.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Corneal Confocal Microscopy subjects | – | Other: Exposure: Corneal nerve fibre morphology by the CCM Procedure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This longitudinal observational cohort study of diagnosis involves follow-up in two study groups: A. Five- to seven-year follow-up re-examination of 5 well-characterized type 1 diabetes (T1D) cohorts (N=516) comprising a neuropathic subset and a non-neuropathic subset. B. Three- to six-year follow-up re-examination of 4 well-characterized type 2 diabetes (T2D) cohorts (N=524) each comprising a neuropathic subset and a non-neuropathic subset. T1D Subjects. The five study sites are composed of cohort studies for T1D initiated between 2008 and 2011. Together, the five sites have studied 516 subjects at baseline with T1D, 363 without DPN and 151 with DPN at baseline. T2D Subjects. Four of the sites have studied subjects with T2D. Together, the four sites have studied 524 subjects at baseline with T2D, 241 without DPN and 283 with DPN at baseline. Of the 1040 total subjects examined in baseline procedures, we anticipate follow-up of 70% for a total re-examined cohort 729.
Key inclusion criteria (4 listed)
- Individuals of any gender or race aged 18 or above
- Type 1 diabetes mellitus or type 2 diabetes mellitus as defined by the American Diabetes Association guidelines (2014) of any duration
- Availability of the initial CCM examination performed two to eight years ago
- Ability to understand and cooperate with study procedures
Key exclusion criteria (3 listed)
- Confirmed to have neuropathy owing to non-diabetic causes (such as familial, alcoholic, nutritional, uremic)
- Current eye infection, corneal damage, or severe movement disorders which could preclude a safe CCM exam
- Allergy to proparacaine (the ocular topical anaesthetic used for the CCM exam)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exposure: Corneal nerve fibre morphology by the CCM ProcedureCCM is a non-invasive method for direct visualization of corneal nerve fibers. Previous research work has confirmed that corneal nerves status correlates with both small and large fibre damage as assessed by quantitative sensory testing and nerve conduction. In the current trial subjects will undergo a bilateral examination of the Bowman's layer of the cornea using the Rostock Cornea Module of the Heidelberg Tomograph III (Heidelberg Engineering, Smithfield RI, USA) to determine their corneal nerve fiber length, corneal nerve fiber density, corneal nerve branch density, and the tortuosity coefficient. Topical anaesthetic and a viscous gel medium will be applied to the eye, which will create a visual gel bridge between the cornea and the sterile single-use cap on the microscope objective lens. After the interface between the corneal epithelium and Bowman's layer is identified, batches of images will be taken and the most technically sound images will be identified and analyzed. | Other | Corneal Confocal Microscopy subjects |
Primary outcome
Evaluate the Concurrent Validity of CCM Parameters from Cross-Sectional Analysis of Well-Characterized T1D and T2D Subjects.
Time frame: Any data obtained from pre-study measurements
Evaluate the Predictive Validity of CCM Parameters based on the 5-7 year Incidence of Neuropathy in Well-Characterized T1D and T2D Subjects Without Neuropathy at Baseline
Time frame: Study visit
Evaluate the Predictive Validity of CCM Parameters for 5-7 year Progression of Neuropathy
Time frame: Study visit
Comparison of Manual versus Automated Image analysis
Time frame: Pre-study and study visit data
1 secondary outcome
Determination of the Factors associated with CCM Parameters and their Longitudinal Change
Time frame: Study visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2019.
- Background: PubMed 25633665Tavakoli M, Ferdousi M, Petropoulos IN, Morris J, Pritchard N, Zhivov A, Ziegler D, Pacaud D, Romanchuk K, Perkins BA, Lovblom LE, Bril V, Singleton JR, Smith G, Boulton AJ, Efron N, Malik RA. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set. Diabetes Care. 2015 May;38(5):838-43. doi: 10.2337/dc14-2311. Epub 2015 Jan 29.
- Background: PubMed 25573881Pritchard N, Edwards K, Russell AW, Perkins BA, Malik RA, Efron N. Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes. Diabetes Care. 2015 Apr;38(4):671-5. doi: 10.2337/dc14-2114. Epub 2015 Jan 8.
- Background: PubMed 25556884Tavakoli M, Begum P, McLaughlin J, Malik RA. Corneal confocal microscopy for the diagnosis of diabetic autonomic neuropathy. Muscle Nerve. 2015 Sep;52(3):363-70. doi: 10.1002/mus.24553. Epub 2015 Jun 18.
- Background: PubMed 25406279Dehghani C, Pritchard N, Edwards K, Vagenas D, Russell AW, Malik RA, Efron N. Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes: development of a potential measure of diabetic peripheral neuropathy. Invest Ophthalmol Vis Sci. 2014 Nov 18;55(12):7982-90. doi: 10.1167/iovs.14-15605.
- Background: PubMed 25251450Maddaloni E, Sabatino F, Del Toro R, Crugliano S, Grande S, Lauria Pantano A, Maurizi AR, Palermo A, Bonini S, Pozzilli P, Manfrini S. In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes. Diabet Med. 2015 Feb;32(2):262-6. doi: 10.1111/dme.12583. Epub 2014 Sep 24.
- Background: PubMed 25044236Stem MS, Hussain M, Lentz SI, Raval N, Gardner TW, Pop-Busui R, Shtein RM. Differential reduction in corneal nerve fiber length in patients with type 1 or type 2 diabetes mellitus. J Diabetes Complications. 2014 Sep-Oct;28(5):658-61. doi: 10.1016/j.jdiacomp.2014.06.007. Epub 2014 Jun 17.
- Background: PubMed 24969581Asghar O, Petropoulos IN, Alam U, Jones W, Jeziorska M, Marshall A, Ponirakis G, Fadavi H, Boulton AJ, Tavakoli M, Malik RA. Corneal confocal microscopy detects neuropathy in subjects with impaired glucose tolerance. Diabetes Care. 2014 Sep;37(9):2643-6. doi: 10.2337/dc14-0279. Epub 2014 Jun 26.
- Background: PubMed 24750318Edwards K, Pritchard N, Vagenas D, Russell A, Malik RA, Efron N. Standardizing corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy. Diabet Med. 2014 Oct;31(10):1205-9. doi: 10.1111/dme.12466. Epub 2014 May 24.
- Background: PubMed 24574045Ziegler D, Papanas N, Zhivov A, Allgeier S, Winter K, Ziegler I, Bruggemann J, Strom A, Peschel S, Kohler B, Stachs O, Guthoff RF, Roden M; German Diabetes Study (GDS) Group. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes. 2014 Jul;63(7):2454-63. doi: 10.2337/db13-1819. Epub 2014 Feb 26.
- Background: PubMed 24569580Petropoulos IN, Alam U, Fadavi H, Marshall A, Asghar O, Dabbah MA, Chen X, Graham J, Ponirakis G, Boulton AJ, Tavakoli M, Malik RA. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Invest Ophthalmol Vis Sci. 2014 Apr 3;55(4):2071-8. doi: 10.1167/iovs.13-13787.
- Background: PubMed 24124944Tavakoli M, Petropoulos IN, Malik RA. Corneal confocal microscopy to assess diabetic neuropathy: an eye on the foot. J Diabetes Sci Technol. 2013 Sep 1;7(5):1179-89. doi: 10.1177/193229681300700509.
- Background: PubMed 23877983Petropoulos IN, Alam U, Fadavi H, Asghar O, Green P, Ponirakis G, Marshall A, Boulton AJ, Tavakoli M, Malik RA. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care. 2013 Nov;36(11):3646-51. doi: 10.2337/dc13-0193. Epub 2013 Jul 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce A Perkins, MD principal investigator
MOUNT SINAI HOSPITAL
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetic Polyneuropathy and Diabetes Mellitus, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada, United States, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the Concurrent Validity of CCM Parameters from Cross-Sectional Analysis of Well-Characterized T1D and T2D Subjects. (time frame: Any data obtained from pre-study measurements). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02423434, which also lists 33 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2019; AzTrials last refreshed its copy on 6 Nov 2026.