Diabetic Peripheral NeuropathyNCT05118217
Microvascular Dysfunction in Diabetic Peripheral Neuropathy
An observational study of Diabetic Peripheral Neuropathy and Painful Diabetic Neuropathy, run by University of Plymouth.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Peripheral Neuropathy, Painful Diabetic Neuropathy
- What is being tested?
- This is a non-interventional study
- How many people
- 72 participants
- Where
- No sites listed yet
- Study dates
- 18 Nov 2021to 30 Apr 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
Study population: Individuals with Type 2 Diabetes and Diabetic Peripheral Neuropathy
Who may be able to join
- 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.
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- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Retinal Microvascular Dysfunction in Non-Painful and Painful Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus
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.
Read more
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.
Read the detailed 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:
- 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
- Being tested
- This is a non-interventional study
- Keywords
- microvascular dysfunction, endothelial dysfunction
- Medical subject headings
- Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
This is a non-interventional studyOther
This is a non-interventional study
| Study group | Role | What they receive |
|---|---|---|
| Clinical DPN without pain | * Score above 2.5 on the Michigan Neuropathy Screening Instrument
* Score below 4 on the DN4 Receives: Other: This is a non-interventional study | |
| Painful DPN | * Score above 2.5 on the MNSI
* Score above 4 on the DN4 Receives: Other: This is a non-interventional study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%).
Measured: during the procedure
Secondary outcomes (8)
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
Measured: during the procedure
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
Measured: during the procedure
Skin Autofluorescence
Outcome Measure: Skin Autofluorescence (AU)
Measured: during the procedure
Transcutaneous Oximetry
TcPO₂ (mmHg)
Measured: during the procedure
Blood pressure
mmHg
Measured: during the procedure
Lipid Profile
HDL and LDL lipid levels - obtained from participants general practitioner with consent
Measured: pre-procedure
HbA1c
As standard - obtained from participants general practitioner with consent
Measured: pre-procedure
Body Mass Index
Body Mass Index
Measured: during the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2021
- Study start18 Nov 2021 (estimated)
- Primary completion30 Apr 2022 (estimated)
- Study completion30 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Peripheral NeuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Plymouth
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Calvin Howorth, University of Plymouth
- Investigators
- Calvin Howorth, BSc (Hons), Principal investigator, University of Plymouth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05118217
- Sponsor's protocol ID
- IRAS: 261329
- Status last verified
- Nov 2021
- First submitted
- 12 Oct 2020
- Last updated
- 11 Nov 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The Chief Investigator will have access to the final dataset. Any study data arising from the conduction of the study will be owned by the Sponsor (University of Plymouth). At the end of trial, anonymised participant level data may be shared with other researchers under an appropriate data sharing agreement. Data shared in this manner will ensure that the identity of all participants are obscured, and anonymity is enshrined in its presentation.
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retinal Microvascular Dysfunction in Non-Painful and Painful Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT05118217
- Acronym / sponsor ID
- IRAS: 261329
- Keywords
- microvascular dysfunction, endothelial dysfunction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of PlymouthUniversity, hospital or other
- Study start
- 18 Nov 2021 (estimated)
- Primary completion
- 30 Apr 2022 (estimated)
- Study completion
- 30 Apr 2022 (estimated)
- First posted
- 11 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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:
- 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
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clinical DPN without pain | – | Other: This is a non-interventional study* Score above 2.5 on the Michigan Neuropathy Screening Instrument * Score below 4 on the DN4 |
| Painful DPN | – | Other: This is a non-interventional study* Score above 2.5 on the MNSI * Score above 4 on the DN4 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Individuals with Type 2 Diabetes and Diabetic Peripheral Neuropathy
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| This is a non-interventional studyThis is a non-interventional study | Other | Clinical DPN without pain, Painful DPN |
Primary outcome
Dynamic Vessel Analysis
Time frame: during the procedure
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%).
8 secondary outcomes
Static Vessel Analysis
Time frame: during the procedure
Retinal Nerve Layer Thickness
Time frame: during the procedure
Skin Autofluorescence
Time frame: during the procedure
Transcutaneous Oximetry
Time frame: during the procedure
Blood pressure
Time frame: during the procedure
Lipid Profile
Time frame: pre-procedure
HbA1c
Time frame: pre-procedure
Body Mass Index
Time frame: during the procedure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
- Individual participant dataSharing planned: Undecided. The Chief Investigator will have access to the final dataset. Any study data arising from the conduction of the study will be owned by the Sponsor (University of Plymouth). At the end of trial, anonymised participant level data may be shared with other researchers under an appropriate data sharing agreement. Data shared in this manner will ensure that the identity of all participants are obscured, and anonymity is enshrined in its presentation.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Calvin Howorth, BSc (Hons) principal investigator
University of Plymouth
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetic Peripheral Neuropathy and Painful Diabetic Neuropathy, run by University of Plymouth.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Calvin Howorth, BSc (Hons) (07508993412, calvin.howorth@plymouth.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dynamic Vessel Analysis (time frame: during the procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.