Characterization and Prediction of Early Onset Diabetic Peripheral Neuropathy

NCT ID: NCT05546138

Last Updated: 2024-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-10-01

Study Completion Date

2029-12-31

Brief Summary

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Predicting early onset neuropathy in people with type 1 diabetes

Detailed Description

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Background

Diabetic peripheral neuropathy is the most common complication to diabetes mellitus affecting as much as 50% of the population with diabetes. Symmetrical sensory neuropathy is by far the most common pattern, which often progress slowly over many years, although some individuals experience faster and more severe courses. Despite the frequent occurrence, the causes of diabetic peripheral neuropathy are largely unknown, which is reflected in the fact that no disease-modifying treatments are available for preventing, treating or even halting the progression of the disease. The consequences can be dire, as neuropathy frequently leads to foot ulcers, amputations or intolerable neuropathic pain in the lower extremities. Sensory loss may go completely undetected in diabetes, as there often are literally no symptoms. For many individuals, the development of diabetic peripheral neuropathy can therefore proceed completely unnoticed, making regular screening the most important tool for diagnosing the condition. Unfortunately, unlike nephropathy or retinopathy, diabetic peripheral neuropathy is not easily screened for, as the condition lacks reliable markers for early- or progressing disease. Therefore, screening for diabetic peripheral neuropathy currently revolves around diagnosing loss of protective sensation, judged by the inability to feel vibration or light touch. However, in their most recent guidelines, the American Diabetes Association has included screening for small fibre neuropathy using either the cold- and heat perception thresholds or pinprick as a clinical standard. Although this acknowledgement of the importance of assessing not only large- but also small nerve fibres is a huge step towards early detection of diabetic peripheral neuropathy, the overriding issue of insensitive, unreproducible, and inaccurate bedside tests for small nerve fibres remains. While cold- and heat perception and pinprick sensation are indeed mediated by small nerve fibres, the sensitivity of these methods, outside of extreme standardization only achievable in dedicated neuropathy research-centres, remain poor and not usable on an individual level. This lack of sensitivity has also become apparent in several large clinical trials, where the methods have continuously failed as robust clinical endpoints. Due to this, the hunt for a sensitive and reproducible method for adequate assessment of the small nerve fibres have begun. Amongst several interesting methods, two have gained particular interest (corneal confocal microscopy and skin biopsies with quantification of intra-epidermal nerve fibre density), due to their diverse strengths, although clinical application is currently limited to a few specialized sites. Furthermore, both methods suffer several inherent issues including that fact that they only provide information about the structure of the nerves and not the function.

In this study, we will therefore combine established gold standards for early detection of structural changes to small nerve fibres in diabetic peripheral neuropathy with cutting-edge, experimental techniques for measuring the function of the same nerve fibres. Furthermore, we will also evaluate several advanced technologies as an alternative to the current clinical standard for large fibre evaluation (biothesiometry).

Study objectives

* To establish a prospective cohort for long-term follow-up for early detection of the development of diabetic peripheral neuropathy
* To evaluate alternative methods for screening for diabetic peripheral neuropathy in a clinical setting
* To evaluate measurements of small nerve fibre function against methods for small nerve fibre structure

Methods

A prospective, long-term, follow-up, cohort study running from 01.04.2022-31.12.2029. The study will consist of two different, yet aligned, sub-studies:

1. An observational, cohort study consisting of a random sample of up to 1,000 persons with diabetes (any type) and neuropathy at any stage, entering the outpatient clinic at Steno Diabetes Center North Denmark/Department of Endocrinology, Aalborg University Hospital.
2. A smaller, observational, cohort study consists of 100-200 persons with type 1 diabetes and no clinically detectable neuropathy.

The first study will aim to evaluate alternative screening methods to be used in clinical practice, while it will also be used to identify persons eligible to participate in the second study.

The second study will aim to preform deep-sensory phenotyping of people without established diabetic peripheral neuropathy using methods evaluating both structure and function of small nerve fibers. The cohort will be followed from inclusion and evaluated once yearly to see if they are progressing. Ultimately, this cohort will be used to retrospectively evaluate, if any, or a combination of, the used experimental methodology can predict, who develops diabetic peripheral neuropathy, and who doesn't.

Participants from either of the two studies will be informed about the trial and their expected outcomes both written and vocally. Participants will follow their usual clinical control for diabetes and complication-screening (including usual foot care and neuropathy screening), and the enhanced screening performed in this study will therefore be an addition to clinical standard. No interventions will be made.

Conditions

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Neuropathy, Diabetic Small Nerve Fiber Neuropathy Type 1 Diabetes

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Type 1 diabetes without known peripheral neuropathy

People with type 1 diabetes without known peripheral neuropathy with "limited" diabetes duration

Skin biopsies with quantification of intra-epidermal nerve fibre density

Intervention Type DIAGNOSTIC_TEST

Skin biopsy

Perception Threshold Tracking

Intervention Type DIAGNOSTIC_TEST

Transcutaneous stimulation of large and small nerve fibres using weak electrical currents

Thermal perception thresholds

Intervention Type DIAGNOSTIC_TEST

Heat and cold perception thresholds

Corneal confocal Microscopy

Intervention Type DIAGNOSTIC_TEST

Corneal nerve fibre density, corneal nerve fibre length, corneal nerve branch density

MRI

Intervention Type DIAGNOSTIC_TEST

Functional and structural MRI pictures of peripheral nerves and CNS

Nerve conduction studies

Intervention Type DIAGNOSTIC_TEST

Nerve conduction and amplitude of Sural nerve

Composite scores and questionnaires

Intervention Type OTHER

Composite scores and questionnaires

Interventions

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Skin biopsies with quantification of intra-epidermal nerve fibre density

Skin biopsy

Intervention Type DIAGNOSTIC_TEST

Perception Threshold Tracking

Transcutaneous stimulation of large and small nerve fibres using weak electrical currents

Intervention Type DIAGNOSTIC_TEST

Thermal perception thresholds

Heat and cold perception thresholds

Intervention Type DIAGNOSTIC_TEST

Corneal confocal Microscopy

Corneal nerve fibre density, corneal nerve fibre length, corneal nerve branch density

Intervention Type DIAGNOSTIC_TEST

MRI

Functional and structural MRI pictures of peripheral nerves and CNS

Intervention Type DIAGNOSTIC_TEST

Nerve conduction studies

Nerve conduction and amplitude of Sural nerve

Intervention Type DIAGNOSTIC_TEST

Composite scores and questionnaires

Composite scores and questionnaires

Intervention Type OTHER

Other Intervention Names

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PGP9.5, antibodies for subsets of ion-channels ect PTT Quantitative Sensory Testing CCM fMRI, DTI, neurography NC-STAT DPNCheck DN4, MNSI, NDS, NAFF

Eligibility Criteria

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Inclusion Criteria

* Men and women aged 18-80 years
* Diagnosed with diabetes (of any type)
* No clinically established diabetic peripheral neuropathy at inclusion

Exclusion Criteria

* Alcohol or drug abuse within the last year (prior to inclusion)
* Chemotherapy (prior or within study period) or experimental medicine
* Severe vitamin deficiencies
* Inability to understand or comply with the examinations
* Planned or likely discontinuation of care at Aalborg University Hospital
* Known hematologic disorders resulting in a markedly reduced ability to stop small bleedings
* Severe limb ischemia
* Active diabetic foot ulcers
* Previous amputations
* Severe skin diseases or diseases known to cause neural damage
* Pregnancy at inclusion
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Aalborg University

OTHER

Sponsor Role collaborator

University of Aarhus

OTHER

Sponsor Role collaborator

Aalborg University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Johan Bovbjerg Røikjer

Primary Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Peter Vestergaard, PhD

Role: STUDY_CHAIR

Steno Diabetes Center North Denmark

Johan M Røikjer, PhD

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center North Denmark

Locations

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Aalborg University Hospital

Aalborg, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Johan M Røikjer, PhD

Role: CONTACT

+45 97663651

Niels Ejskjaer, PhD

Role: CONTACT

+45 +4597663656

Facility Contacts

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Johan Røikjer, MD, PhD

Role: primary

97666092 ext. +45

Related Links

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https://stenodiabetescenter.rn.dk/

Steno Diabetes Center North Denmark

Other Identifiers

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N-20220013

Identifier Type: -

Identifier Source: org_study_id

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