Diabetic Neuropathy Screening Study 1.1 + Substudy 1.2-1.3-1.4

NCT05043636 | Unknown

• 1 other identifier: H-10929796
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this project is to describe the prevalence of and risk factors to diabetic neuropathy in a representative cohort of diabetes patients and to investigate pathophysiological conditions in those patients with neuropathy. This project will yield substantial new knowledge about the prevalence of diabetic neuropathy in type 1 and type 2 DM persons, new risk factors to neuropathy and the association to other diabetic complications. Findings related to the study may facilitate new treatment regimens prompting a better neuropathy treatment with reduced incidence of diabetic complications. First patients at SDCC will be screened for diabetic neuropathy (Study 1.1) with an extended neuropathy screening program as an addition to the routine neuropathy screening at SDCC. 1000 patients with type 1 DM and 1000 patients with type 2 DM will be included. This screening study is a prerequisite for the further study of study participants in substudies investigating associations between diabetic neuropathy and diabetic complications as described below. Hypothesis: Several patients with diabetes have undiagnosed neuropathy and associated diabetic complications. We hypothesize that diabetic neuropathy is underdiagnosed at SDCC and can be diagnosed with targeted screening with new and traditional measuring techniques. In addition, several patients may have complications related to neuropathy, including foot complications, and dysregulation of glucose metabolism Aim: This study consists of a screening study (study 1.1) and two substudies (1.2 and 1.3 ). Study 1.1 is a cross-sectional study describing the prevalence of diabetic neuropathy based on questionnaire data and objective measures as described below and associated diabetic complications including foot complications. The primary aim is to explore the prevalence of diabatic neuropathy in patients with type 1 and type 2 DM at SDCC and secondarily to explore associations between diabetic neuropathy and complications, as described in the respective sections below. The substudy 1.2 is an observational single center cohort study with the aim of investigating associations between neuropathy diagnosed with new devices for measurement of neuropathy and foot complications in patients with type 1 and type 2 diabetes. The substudy 1.3 is an observational single center cohort study investigating the association between CAN and glycemic variability in patients with type 1 diabetes.

Conditions

Diabetic Neuropathies; Distal Peripheral Sensory Neuropathy; Diabetic Foot; Foot Deformities; Autonomic Neuropathy; CAN

Keywords

vagus; sudoscan; rolltemp; hearttrends; pinprick; monofilament; MNSI; DN4

Outcome Measures

Primary Outcomes (7)

• Peripheral Neuropathy assesed by DPN-check

  Neuropathy assesed by DPN-check: Sural Nerve conduction velocity(m/s) of the Sural nerves by DPN-check.

  18.10.2019-31.12.2022

• Autonomic Neuropathy assesed by Sudoscan

  Neuropathy assesed by Sudoscan: Peripheral small-fiber sympathetic function (Sudoscan), measuring sudomotor function by electrochemical skin conductance (µS) in feet

  18.10.2019-31.12.2022

• Peripheral Neuropathy assesed by Biothesiometer

  Neuropathy assesed by Biothesiometer: Peripheral vibration sensation (volt)

  18.10.2019-31.12.2022

• Peripheral Neuropathy assesed by Roll-temp

  Neuropathy assesed by Roll-temp: Cold and warm sense of foot and lower leg by

  18.10.2019-31.12.2022

• Peripheral Neuropathy assesed by Monofilament

  Neuropathy assesed by Monofilament Light touch with 10 and 75 g monofilament

  18.10.2019-31.12.2022

• Peripheral Neuropathy assesed by Pinprick

  Neuropathy assesed by Pinprick: Pain Sensation with a 40g needle

  18.10.2019-31.12.2022

• Cardivascular Autonomic Neuropathy assesed by Vagus

  The examination consists of 4 measures, all aimed at measuring heart rate. Measurements are taken for 5 minutes rest, change of position from lying to standing position, during deep breathing and by Valsalva (by breathing in a mouthpiece with a 40 mmHg resistance).

  18.10.2019-31.12.2022

Secondary Outcomes (5)

• Peripheral Neuropathy assesed by DPN-check

  18.10.2019-31.12.2022

• Autonomic Neuropathy assesed by Sudoscan

  18.10.2019-31.12.2022

• Pressure pain sensitivity

  18.10.2019-31.12.2022

• Oxygen Saturation in supine and standing position

  18.10.2019-31.12.2022

• Blood pressure in supine and standing position

  18.10.2019-31.12.2022

Interventions

Vagus DEVICE

Cardiovascular autonomic neuropathy (Vagus) both resting heart rate variability and cardiovascular reflex tests The examination consists of 4 measures, all aimed at measuring heart rate. Measurements are taken for 5 minutes rest, change of position from lying to standing position, during deep breathing and by Valsalva (by breathing in a mouthpiece with a 40 mmHg resistance).

HeartsTrends DEVICE

• Cardiovascular autonomic neuropathy (HeartTrends®) measurers 60-minutes heart rate variability via a chest belt electrode (a Holter monitor) and an external data acquisition device.

Sudoscan DEVICE

Peripheral small-fiber sympathetic function (Sudoscan), measuring sudomotor function by electrochemical skin conductance in hands and feet

UllMeter DEVICE

• Pressure pain sensitivity of the chest bone is recorded (with a device which has the size and shape as a pen)during rest as a measure for sympathetic autonomic activity of the brain (UllMeter®) (www.stressmeter.org)

DPN-check DEVICE

Nerve conduction velocity and amplitude of the Sural nerves by DPN-check

Rolltemp DEVICE

Cold and warm sense of foot and lower leg

Dexcom G6 Device DEVICE

Insertion of continuous glucose monitor ( The Dexcom G6 Device) After 10 days in the study the patient will return the glucose monitor and diary by prepaid mail. Glycemic variability and hypoglycemia duration will be calculated from CGM data. Glycemic variability will be assessed by standard deviation (SD) and Coefficient of Variance (CV). We define normo-glycemic range as sensor glucose between 4.0 and 10.0 mmol/L. Hypoglycemia will be defined in two ranges as SG ≤3.9 mmol/L or SG ≤3.0 mmol/L). An episode of hypoglycemia will be defined as at least 15 minutes with SG below 3.9 mmol/L or 3.0 mmol/L, respectively. CGM recordings with less than 72 hours of data will be excluded from analysis.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Persons with type 1 and type 2 DM attending Diabetes Mellitus treatment at Steno Diabetes Center Copenhagen will be invited to participate in this study. The persons will be recruited by receiving a letter describing the study.

You may qualify if:

• The ability to give informed consent
• Male or female persons \>18 years of age with a diagnosis of type 1 or type 2 DM (WHO criteria)

You may not qualify if:

• Ongoing cancer treatment or other concurrent illness that will make the participant unable to attend the study on the discretion of the investigator
• Pregnant or breastfeeding persons
• Persons who, in the judgement of the investigator, may not be able to follow protocol
• Persons in active laser treatment for retinopathy, will be excluded from only Valsalva test (part of CAN measurements)
• Persons with atrial fibrillation, atrial flutter or pacemakers will not be subjected to CAN measurements.
• The ability to give informed consent
• Male or female participants \>39 years of age with a diagnosis of type 1 or type 2 diabetes (WHO criteria)
• Peripheral neuropathy diagnosed by either:
• Biothesiometry above age-stratified threshold values (150 participants) and/or abolished sensation to monofilament (10g) or
• Sudoscan and/or DPNCheck values below age-stratified threshold values (150 participants)
• Ongoing cancer treatment or other concurrent illness that will make the patient unable to attend the study on the discretion of the investigator
• Pregnant or breastfeeding participants
• Participants who, in the judgement of the investigator, may not be able to follow the protocol
• Participants in active laser treatment for retinopathy, will be excluded from only Valsalva test (part of Vagus™ measurements)
• Participants with atrial fibrillation, atrial flutter or pacemakers will not be subjected to CAN measurements.

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biological material to a biobank for future research

MeSH Terms

Conditions

Diabetic Neuropathies; Diabetic Foot; Foot Deformities

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: September 14, 2021
• Study Start: September 1, 2019
• Primary Completion: October 18, 2019
• Study Completion: December 31, 2022
• Last Updated: September 14, 2021

Record last verified: 2021-05

Locations

DK (1)