Microvascular Dysfunction in Diabetic Peripheral Neuropathy

NCT05118217 | Unknown

• 1 other identifier: IRAS: 261329
• Study Type: observational
• Target: 72
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study primarily seeks to evaluate dysfunction of small blood vessels and their linkage to dysfunction of nerves in people with Type 2 Diabetes. The purpose of this research is to explore some of the underlying pathophysiology of diabetic peripheral neuropathy, particularly painful diabetic peripheral neuropathy. The pain experienced by individuals with painful diabetic peripheral neuropathy is severe and associated with low quality of life. The pain does not typically respond well to pharmacological management. The processes underpinning the sources of pain are poorly understood, consequently only around a third of patients benefit from existing treatments. Some historic research on the sources of pain suggest the retention of the ability to reduce blood flow in small vessels may underpin these pain pathways. This research aims to explore this possibility, looking at the nerve-linked response in small vessels with a flickering light within the eye. Participants will complete three or four questionnaires: one demographic, two to aid with stratifying participants into groups concerning symptoms of neuropathy and an additional questionnaire if participants are stratified to the painful DPN group. A basic neurological examination of the feet will follow. Basic measurements of height, weight and blood pressure will be recorded for each participant. The primary sites of measurement of this small vessel dysfunction will be the eye and the foot investigated in a non-invasive manner. A bright flickering light will be shone into participants eyes, with the reaction of small vessels recorded. Sensors will also be placed on the feet and chest of participants and warmed to \~44C. An image will be taken of participants eyes to measure nerve layer thickness and an area of skin on the forearm will be illuminated to measure for levels of a metabolic marker. A picture of the eye will also be taken to determine nerve layer thickness.

Conditions

Diabetic Peripheral Neuropathy; Painful Diabetic Neuropathy

Keywords

microvascular dysfunction; endothelial dysfunction

Outcome Measures

Primary Outcomes (1)

• Dynamic Vessel Analysis

  Retinal vasodilation in response to flicker light stimulus - Response will be recorded as baseline corrected flicker response (bFR). Baseline will be recorded as the period from -30 to -5 seconds prior to flicker light stimulation. bFR will be calculated as the difference between peak dilation after provocation (dil%) and the minimum of the subsequent reactive constriction (constr%) and the width of the baseline amplitude (width BL%).

  during the procedure

Secondary Outcomes (8)

• Static Vessel Analysis

  during the procedure

• Retinal Nerve Layer Thickness

  during the procedure

• Skin Autofluorescence

  during the procedure

• Transcutaneous Oximetry

  during the procedure

• Blood pressure

  during the procedure

Study Arms (2)

Clinical DPN without pain

* Score above 2.5 on the Michigan Neuropathy Screening Instrument * Score below 4 on the DN4

Other: This is a non-interventional study

Painful DPN

* Score above 2.5 on the MNSI * Score above 4 on the DN4

Other: This is a non-interventional study

Interventions

This is a non-interventional study OTHER

This is a non-interventional study

Clinical DPN without pain; Painful DPN

Eligibility Criteria

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

Study Population

Individuals with Type 2 Diabetes and Diabetic Peripheral Neuropathy

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study
• Male or Female, aged 18 years or above.
• Diagnosed with Type 2 Diabetes Mellitus (confirmed on clinical notes)
• History of an abnormal neurovascular testing result (typically, 10g monofilament test)
• Able (in the Investigators opinion) and willing to comply with all study requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
• Must be willing to refrain from caffeine and tobacco consumption 24hrs before procedures are undertaken.
• Participants must be willing and able (in the Investigator's opinion) to undertake DN4, Brief Pain Inventory-DPN and Michigan Neuropathy Screening Instrument questionnaires.
• Able to lie flat

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• Patients with neuropathy due to other aetiological causes, such as hereditary, metabolic, inflammatory, cervical and lumbar spine diseases; cerebrovascular diseases; uremia; alcohol use; or toxic factors.
• All patients with Type 1 diabetes.
• A positive history of malignancy; connective tissue or infectious disease;
• Deficiency of vitamin B12 or folate;
• Chronic renal failure;
• Liver failure;
• Glaucoma;
• Age-related macular degeneration
• Epilepsy;
• Severely sight-impaired
• Presence of a neurological disorder;
• Inflammatory arthropathies
• Pregnancy.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

Sponsors & Collaborators

• University of Plymouth: lead

MeSH Terms

Conditions

Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Calvin Howorth, BSc (Hons)

  University of Plymouth

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Calvin Howorth, BSc (Hons)

CONTACT

07508993412; calvin.howorth@plymouth.ac.uk

Leanne Smewing, PhD

CONTACT

01752 587 541; leanne.smewing@plymouth.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator/Lecturer of Podiatry

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: November 11, 2021
• Study Start: November 18, 2021
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2022
• Last Updated: November 11, 2021

Record last verified: 2021-11