Microvascular Dysfunction in Diabetic Peripheral Neuropathy

Diabetic Peripheral Neuropathy Clinical Trial

Official title:

Retinal Microvascular Dysfunction in Non-Painful and Painful Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05118217
• Other study ID #: IRAS: 261329
• Status: Not yet recruiting
• Start date: November 18, 2021
• Est. completion date: April 30, 2022

Study information

• Verified date: November 2021
• Source: University of Plymouth
• Contact: Calvin Howorth, BSc (Hons)
• Phone: 07508993412
• Email: calvin.howorth[@]plymouth.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

This cross-sectional observational study will take place between November 2021 and May 2022 and will recruit individuals with Type 2 Diabetes alongside painful or non-painful peripheral neuropathy. The study aims to determine the relationship between microvascular and metabolic markers and i) clinical neuropathy, ii) of painful neuropathy and iii) severity of neuropathic pain within a Type 2 Diabetic cohort.

This will be done through achieving the following objectives:

i) determination of whether retinal vasodilation in response to flicker-light stimulus is associated with i) the severity of neuropathy, ii) the presence of painful neuropathy and iii) severity of neuropathic pain within a T2DM cohort.

ii) determination of whether levels of tissue-bound advanced glycation endproducts (AGEs) measured by skin autofluorescence are associated with i) the severity of neuropathy, ii) the presence of painful neuropathy and iii) severity of neuropathic pain within a T2DM cohort.

iii) determination of whether pedal skin transcutaneous oxygen tension (TcPO2) measured by transcutaneous oximetry is associated with i) the severity of neuropathy, ii) the presence of painful neuropathy and iii) severity of neuropathic pain within a T2DM cohort.

iv)determination of whether retinal nerve layer thickness is associated with the severity of neuropathy, the presence of painful neuropathy and severity of neuropathic pain within a T2DM cohort v)determination of whether the following factors are associated with the severity of neuropathy, the presence of painful neuropathy and severity of neuropathic pain within a T2DM cohort

• HbA1c

• Lipid profile

• Body Mass Index

• Blood Pressure

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 72
• Est. completion date: April 30, 2022
• Est. primary completion date: April 30, 2022
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

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.

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Peripheral Neuropathy
• Pain
• Painful Diabetic Neuropathy
• Peripheral Nervous System Diseases

Intervention

Other:
• This is a non-interventional study
This is a non-interventional study

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Plymouth

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Static Vessel Analysis	The standard parameters for Static Retinal Vessel Function observed will be as follows: Diameter of the central retinal artery equivalent (CRAE); Diameter of the central retinal vein equivalent (CRVE); The ratio of CRAE-CRVE expressed as the arterio-venous ratio (AVR); Outcome Measure: AVR	during the procedure
Secondary	Retinal Nerve Layer Thickness	A measure of central retinal nerve fibre layer (RNFL) thickness will be obtained using the Heidelberg Spectralis OCT. This is a commercially available, non-invasive device that provides a high resolution scan of the retinal layers.; Outcome Measure: Retinal Nerve Layer Thickness	during the procedure
Secondary	Skin Autofluorescence	Outcome Measure: Skin Autofluorescence (AU)	during the procedure
Secondary	Transcutaneous Oximetry	TcPO2 (mmHg)	during the procedure
Secondary	Blood pressure	mmHg	during the procedure
Secondary	Lipid Profile	HDL and LDL lipid levels - obtained from participants general practitioner with consent	pre-procedure
Secondary	HbA1c	As standard - obtained from participants general practitioner with consent	pre-procedure
Secondary	Body Mass Index	Body Mass Index	during the procedure