NCT04078516

Brief Summary

MEDON aims to examine new methods for early detection and grading of diabetic peripheral neuropathy focusing on both small- and large nerve fibers. Furthermore, MEDON aims to describe differences between people with classic diabetic peripheral neuropathy and those with painful diabetic neuropathy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Aug 2019

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 12, 2019

Completed
16 days until next milestone

First Submitted

Initial submission to the registry

August 28, 2019

Completed
9 days until next milestone

First Posted

Study publicly available on registry

September 6, 2019

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2021

Completed
Last Updated

November 2, 2021

Status Verified

November 1, 2021

Enrollment Period

2.1 years

First QC Date

August 28, 2019

Last Update Submit

November 1, 2021

Conditions

Keywords

diabetesneuropathyearly detectionsmall nerve fibers

Outcome Measures

Primary Outcomes (1)

  • Diagnostic value of CCM, PTT, AF and MRI

    Using Quantitative Sensory Testing (small fibers) and conventional nerve conduction studies (large fibers) as golden standards, we will determine the prognostic value of: Perception Threshold Tracking Corneal Confocal Microscopy Axon-flair mediated response MRI-scans in detecting neuropathy. Sensitivity and specificity will be reported. OBS! Tests will be tested in the initial groups and AFTER a group re-arrangement based on results from QST and NCS.

    End of study (when all patients have completed all sessions. Latest 31. december 2021)

Secondary Outcomes (1)

  • Validation of PainDETECT in diabetes

    End of study / end of inclusion (when all patients have completed the screening session. Latest 31. november 2021)

Other Outcomes (1)

  • Exploratory measures

    End of study (latest december 31 2021).

Study Arms (4)

Type 1 diabetes and painful neuropathy

No interventions. A series of observationel/expirimental methods for detecting and grading neuropathy will be applied.

Diagnostic Test: Perception Threshold Tracking (PTT)Diagnostic Test: Axon-flair mediated responsDiagnostic Test: Heart rate variabilityDiagnostic Test: Quantitative Sensory Testing (QST)Diagnostic Test: Peripheral blood pressure and transcutaneous oxygen tensionDiagnostic Test: Magnetic Resonance Imaging (MRI)Diagnostic Test: QuestionnairesDiagnostic Test: Corneal Confocal Microscopy /CCM)

Type 1 diabetes and non-painful neuropathy

No interventions. A series of observationel/expirimental methods for detecting and grading neuropathy will be applied.

Diagnostic Test: Perception Threshold Tracking (PTT)Diagnostic Test: Axon-flair mediated responsDiagnostic Test: Heart rate variabilityDiagnostic Test: Quantitative Sensory Testing (QST)Diagnostic Test: Peripheral blood pressure and transcutaneous oxygen tensionDiagnostic Test: Magnetic Resonance Imaging (MRI)Diagnostic Test: QuestionnairesDiagnostic Test: Corneal Confocal Microscopy /CCM)

Type 1 diabetes and no neuropathy

No interventions. A series of observationel/expirimental methods for detecting and grading neuropathy will be applied.

Diagnostic Test: Perception Threshold Tracking (PTT)Diagnostic Test: Axon-flair mediated responsDiagnostic Test: Heart rate variabilityDiagnostic Test: Quantitative Sensory Testing (QST)Diagnostic Test: Peripheral blood pressure and transcutaneous oxygen tensionDiagnostic Test: Magnetic Resonance Imaging (MRI)Diagnostic Test: QuestionnairesDiagnostic Test: Corneal Confocal Microscopy /CCM)

Matched controls without diabetes

No interventions. A series of observationel/expirimental methods for detecting and grading neuropathy will be applied.

Diagnostic Test: Perception Threshold Tracking (PTT)Diagnostic Test: Axon-flair mediated responsDiagnostic Test: Heart rate variabilityDiagnostic Test: Quantitative Sensory Testing (QST)Diagnostic Test: Peripheral blood pressure and transcutaneous oxygen tensionDiagnostic Test: Magnetic Resonance Imaging (MRI)Diagnostic Test: QuestionnairesDiagnostic Test: Corneal Confocal Microscopy /CCM)

Interventions

low-current electrical stimulation of both large- and small nerve fibers.

Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy

Laser-doppler examination of small blood vessels in the peripheral skin.

Also known as: Laser-doppler
Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy
Heart rate variabilityDIAGNOSTIC_TEST

4 measurements of heart rate.

Also known as: Vagus TM
Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy

Seven tests measuring 13 parameters including heat- and cold-detection and pain thresholds, mechanical pain treshold, mechanical detection threshold, pressure pain treshold and vibration threshold.

Also known as: German Research Network on Neuropathic Pain (DFNS) standard protocol
Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy

Ankle/brachial index, toe/brachial index, TcpO2.

Also known as: Perimed 6000
Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy

MRI-scans of peripheral nerves and the central nervous system. Blood oxygen level dependent (BOLD) MRI.

Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy
QuestionnairesDIAGNOSTIC_TEST

Questionnaires for detecting painful neuropathy

Also known as: PainDETECT, Douleur Neuropathique 4
Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy

Confocal microscopy of the cornea measuring NBD, NFD, NFL

Matched controls without diabetesType 1 diabetes and no neuropathyType 1 diabetes and non-painful neuropathyType 1 diabetes and painful neuropathy

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

The study population include four well-defined groups of subjects: 1. Patients with Type 1 diabetes and painful diabetic peripheral neuropathy (DPN). 2. Patients with Type 1 diabetes and non-painful diabetic peripheral neuropathy (DPN) 3. Patients with Type 1 diabetes and without diabetic peripheral neuropathy (VPT\<15) (DPN). 4. Healthy control subjects matched for age, BMI, and gender. Diabetes duration, HbA1c, insulin use, ethnicity, and co-morbidities will be matched between group 1, 2 and 3 to best ability.

You may qualify if:

  • Men and women minimum 18 years of age and maximum 75 years of age
  • Signed informed consent form
  • Diagnosed with diabetes type I (for group 1-3)
  • Diagnosed with DPN defined as a threshold above 25-volt biothesiometry or absent feeling on the big toe using 10g-monofilament. (for group 1-2)
  • Answered questionnaire: PainDETECT
  • Nothing abnormal on initial tests (group 4)
  • Accepted initial screening blood samples
  • MRI-compatible participant

You may not qualify if:

  • \. Current or previous alcohol- or drug abuse 2. Abnormal screening blood samples 3. Not being able to understand Danish written and/or verbally 4. Not being able to corporate to examination (e.g. not being able to speak, suffering from senile dementia etc.) 5. Previous chemotherapy or intake of experimental medicine 6. Active HSV- or VZV-infection or known HIV 7. Known severe skin disease 8. Known neural damage or disease in the neural system (e.g. MS, Guillain-Barre etc.) 9. Critical limb ischemia defined as in current clinical consensus 10. Allergy or intolerance to histamine or inability to make do without for one day 11. Pregnancy 12. Active cancer-disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Aalborg University Hospital

Aalborg, North Denmark, 9000, Denmark

Location

Related Publications (3)

  • Moussa F, Taleb S, Borbjerg MK, Croosu SS, Morch CD, Frokjaer JB, Hansen TM, Ejskjaer N, Roikjer J. Corneal Immune Cells and Their Relation to Diabetic Peripheral Neuropathy and Neuropathic Pain. Muscle Nerve. 2026 Jan;73(1):72-78. doi: 10.1002/mus.70061. Epub 2025 Nov 17.

  • Roikjer J, Croosu SS, Sejergaard BF, Hansen TM, Frokjaer JB, Sondergaard CB, Petropoulos IN, Malik RA, Nielsen E, Morch CD, Ejskjaer N. Diagnostic Accuracy of Perception Threshold Tracking in the Detection of Small Fiber Damage in Type 1 Diabetes. J Diabetes Sci Technol. 2024 Sep;18(5):1157-1164. doi: 10.1177/19322968231157431. Epub 2023 Feb 24.

  • Roikjer J, Croosu SS, Frokjaer JB, Hansen TM, Arendt-Nielsen L, Ejskjaer N, Morch CD. Perception threshold tracking: validating a novel method for assessing function of large and small sensory nerve fibers in diabetic peripheral neuropathy with and without pain. Pain. 2023 Apr 1;164(4):886-894. doi: 10.1097/j.pain.0000000000002780. Epub 2022 Sep 19.

MeSH Terms

Conditions

Diabetic NeuropathiesNeuropathy, PainfulDiabetes Mellitus

Interventions

Laser-Doppler FlowmetryMagnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Peripheral Nervous System DiseasesNeuromuscular DiseasesNervous System DiseasesDiabetes ComplicationsEndocrine System DiseasesGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, CardiovascularDiagnostic Techniques and ProceduresDiagnosisRheologyInvestigative TechniquesTomographyDiagnostic Imaging

Study Officials

  • Niels Ejskjær, Professor

    Steno Diabtes Center North Denmark, Aalborg University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Endocrinology

Study Record Dates

First Submitted

August 28, 2019

First Posted

September 6, 2019

Study Start

August 12, 2019

Primary Completion

August 31, 2021

Study Completion

August 31, 2021

Last Updated

November 2, 2021

Record last verified: 2021-11

Data Sharing

IPD Sharing
Will share

Data will be shared with collaborating department: Department of Radiology with the purpose of analyzing the data and comparing it to their MRI scans. Data will be shared with Aalborg University with the purpose of analyzing data.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
During and after the study. Data will be available no longer than needed for analyzing.
Access Criteria
anonymized data

Locations