Diabetic Small Fiber Neuropathy: Clinical, Electrophysiological and Neurosonographic Study

April 8, 2024 updated by: Ahmed Sami Alkotami, Tanta University
The aim of work is to study the clinical, electrodiagnostic and neurosonographic characteristics of diabetic patients with small fiber neuropathy in the Egyptian population, and to evaluate both the diagnostic and the prognostic impact of the studied factors on the neuropathy severity and quality of life.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This case-control observational study is aiming to evaluate patients with diabetic small fiber neuropathy in the Egyptian.

Diabetic small fiber neuropathy was defined as both of the following:

A. Typical clinical symptoms of SFN such as burning or sharp pain in toes and feet, and on clinical examination: loss of small fiber modalities (pinprick and temperature), hyperalgesia, allodynia, and/or autonomic signs.

B. Reduced intraepidermal nerve fiber density (IENFD) in distal leg skin punch biopsy.

The study includes 3 groups:

Group I: Patients with diabetic small fiber neuropathy Group II (Control Group): Patients with diabetic mixed small and large fiber neuropathy Group III (Control Group): Subjects without peripheral neuropathy

Clinical evaluation includes: Neuropathic Pain 4 (DN4) questionnaire, 11-point Numeric Pain Scale (NPS), Utah Early Neuropathy Scale (UENS), Toronto Clinical Neuropathy Scale (TCNS), Composite Autonomic Symptom Score (COMPASS-31), an Arabic version, and several anthropometric measures; including: body weight in kilograms, height in centimeters, waist circumference measured in centimeters at the top of the iliac crest, and systolic "SBP" and diastolic "DBP" blood pressure measurement in mmHg.

Electrodiagnostic evaluation includes: routine nerve conduction study, cutaneous silent period by stimulating left median nerve and right sural nerve and recording from the abductor pollicis brevis and tibialis anterior muscles, respectively, bilateral hand-to hand and foot-to-foot sympathetic skin response, and Ewing battery using R-R interval analysis, in addition to the blood pressure tests.

Neurosonographic evaluation includes: bilateral vagal nerve scan at the mid-neck lateral to the thyroid cartilage, left median and right ulnar nerves scan at the mid-forearm, left tibial nerve at the distal ankle 2 to 4 fingerbreadths proximal to the medial malleolus, and right sural nerve 2 to 4 fingerbreadths proximal to the lateral malleolus. Nerves are evaluated for transverse cross-sectional area (CSA).

Severity and outcome measures are assessed using: NPS, TCNS, COMPASS-31, and the index score of Euro Quality of Life -5 Dimensions -5 Levels (EuroQOL-5D-5L), the Arabic version.

Study Type

Observational

Enrollment (Actual)

45

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Kafr Ash Shaykh, Egypt, 33511
        • Ahmed Sami Mahmoud Alkotami

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Group I: Patients with diabetic small fiber neuropathy Group II: Patients with diabetic mixed small and large fiber neuropathy Group III: Subjects without neuropathy

Description

Inclusion Criteria:

  1. Patients diagnosed with diabetes mellitus or impaired glucose intolerance by laboratory investigations including any of the following: HbA1C, fasting blood sugar and 2-hour post prandial blood sugar, and/or antidiabetic medication.

  2. Patients presented with small fiber neuropathy (SFN), including all the following:

    A. Typical clinical symptoms of SFN such as burning or sharp pain in toes and feet, and on clinical examination: loss of small fiber modalities (pinprick and temperature), hyperalgesia, allodynia, and/or autonomic signs.

    B. Reduced intraepidermal nerve fiber density (IENFD) in distal leg skin punch biopsy.

  3. Age older than 18 years old

Exclusion Criteria:

  1. Mental illness that made interviewing ineffective
  2. Physical illness leading to language and/or cognitive barrier
  3. Other conditions that could cause neuropathy (e.g., chemotherapy, alcohol intake, established vitamin B12 deficiency, established hereditary neuropathy "or first-degree family members", active malignancy, chronic advanced liver or kidney diseases thought to cause neuropathy and history of bariatric surgery).
  4. Atrial Fibrillation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with diabetic small fiber neuropathy
Diabetic Patients presented with pure small fiber neuropathy.
Diagnostic test: Clinical Evaluation/Questionnaires
Anthropometric measures, somatosensory assessment (NPS, UENS, TCNS), autonomic assessment (COMPASS-31, Ewing battery), and severity and quality of life evaluation (NPS, TCNS, COMPASS-31, and EuroQOL-5D-5L index score)
Diagnostic test: Nerve Conduction Study
Routine Nerve Conduction Study.
Diagnostic test: Small fiber electrodiagnostic tests
R-R interval analysis, Cutaneous Silent Period and Sympathetic Skin Response.
Diagnostic test: Nerve Ultrasound
Bilateral vagal, left median, right ulnar, left tibial and right sural nerves ultrasound.
Diagnostic test: Skin Biopsy
distal leg 3mm punch skin biopsy
Patients with diabetic mixed small and large fiber neuropathy
Diabetic Patients presented with mixed small and large fiber neuropathy
Diagnostic test: Clinical Evaluation/Questionnaires
Anthropometric measures, somatosensory assessment (NPS, UENS, TCNS), autonomic assessment (COMPASS-31, Ewing battery), and severity and quality of life evaluation (NPS, TCNS, COMPASS-31, and EuroQOL-5D-5L index score)
Diagnostic test: Nerve Conduction Study
Routine Nerve Conduction Study.
Diagnostic test: Small fiber electrodiagnostic tests
R-R interval analysis, Cutaneous Silent Period and Sympathetic Skin Response.
Diagnostic test: Nerve Ultrasound
Bilateral vagal, left median, right ulnar, left tibial and right sural nerves ultrasound.
Diagnostic test: Skin Biopsy
distal leg 3mm punch skin biopsy
Subjects without neuropathy
Healthy subjects without any symptoms and/or signs suggesting neuropathy, and within average IENFD on skin biopsy.
Diagnostic test: Clinical Evaluation/Questionnaires
Anthropometric measures, somatosensory assessment (NPS, UENS, TCNS), autonomic assessment (COMPASS-31, Ewing battery), and severity and quality of life evaluation (NPS, TCNS, COMPASS-31, and EuroQOL-5D-5L index score)
Diagnostic test: Nerve Conduction Study
Routine Nerve Conduction Study.
Diagnostic test: Small fiber electrodiagnostic tests
R-R interval analysis, Cutaneous Silent Period and Sympathetic Skin Response.
Diagnostic test: Nerve Ultrasound
Bilateral vagal, left median, right ulnar, left tibial and right sural nerves ultrasound.
Diagnostic test: Skin Biopsy
distal leg 3mm punch skin biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demonstrate the findings of UENS in the studied groups
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of Utah early neuropathy scale in the studied groups to screen for neuropathic symptoms, where overall scores of 4 and more are considered positive.
through study completion, an average of 9 months
Demonstrate the findings of TCNS in the studied groups
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of Toronto clinical neuropathy scale in the studied groups, to screen for the neuropathic symptoms where overall scores of 6 and more are considered positive.
through study completion, an average of 9 months
Demonstrate the findings of EuroQOL-5D-5L in the studied groups
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of Euro quality of life -5 dimensions -5 levels scale in the studied groups, where lesser scores suggest a lower overall quality of life.
through study completion, an average of 9 months
Demonstrate the findings of nerve conduction studies protocol of the performed nerves in the studied groups.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of nerve conduction studies (NCS) to define neuropathy in the studied groups, which include: unilateral sensory studies of sural, superficial peroneal and ulnar nerves, and motor studies of tibial, peroneal, and ulnar motor nerves with ulnar and tibial F wave latencies. Nerves were evaluated according to a recommended protocol for NCS postulated by the American Academy of Neurology in conjunction with the American Association of Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation, which include an abnormality of any nerve conduction attribute is in two separate nerves, one of which must be the sural nerve.
through study completion, an average of 9 months
Demonstrate the findings of cutaneous silent period in the studied groups.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of cutaneous silent period on stimulating left median nerve and recording from the left abductor pollicis brevis muscle, and on stimulating right sural nerve and recording from the tibialis anterior muscle, where abnormal results in encountered when there is delayed onset and/or end latencies, and/or decreased or absent duration.
through study completion, an average of 9 months
Demonstrate the findings of sympathetic skin response in the studied groups.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of sympathetic skin response on hand-to-hand stimulation of both median nerves, and foot-to-foot stimulation of both tibial nerves, where abnormal result is encountered when there is absent response, or delayed onset latency and/or decreased amplitude.
through study completion, an average of 9 months
Demonstrate the findings of Ewing battery in the studied groups.
Time Frame: through study completion, an average of 9 months

Demonstrate the findings of Ewing battery in the studied groups, where findings are recorded in all the 5 domains of the battery as normal or borderline or abnormal. Total score ranges from 0-5, and cardiovascular autonomic neuropathy is diagnosed according to the findings o fthe battery, where the findings are classified as follows

  • Normal: If all tests are normal, or one test is borderline.
  • Early: One heart rate test is abnormal or two are borderline.
  • Definite: At least two heart rate tests are abnormal
  • Severe: At least two heart rate tests are abnormal plus either at least one blood pressure test is abnormal or both tests are borderline.
  • Atypical: Any other undefined combination.

Further simplified classification is either normal (including normal or early findings) and abnormal (including definite, severe and atypical findings).
through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound CSA of both vagal nerves.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound cross-sectional area of both vagal nerves scanned opposite to the cricoid cartilage in the studied groups.
through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound CSA of right sural nerve.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound cross-sectional area of right sural nerve at the distal calf in the studied groups.
through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound CSA of left tibial nerve.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound cross-sectional area of left tibial nerve at the distal calf in the studied groups.
through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound CSA of left median nerve.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound cross-sectional area of left median nerve at the mid-forearm in the studied groups.
through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound CSA of right ulnar nerve.
Time Frame: through study completion, an average of 9 months
Demonstrate the findings of nerve ultrasound cross-sectional area of right ulnar nerve at the mid-forearm in the studied groups.
through study completion, an average of 9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diabetic neuropathy severity assessment using NPS
Time Frame: through study completion, an average of 9 months
Diabetic neuropathy severity assessment using 11-item Numeric Pain Scale overall score.
through study completion, an average of 9 months
Diabetic neuropathy severity assessment TCNS
Time Frame: through study completion, an average of 9 months
Diabetic neuropathy severity assessment using Toronto clinical neuropathy scale, overall score.
through study completion, an average of 9 months
Diabetic neuropathy severity assessment using COMPASS-31
Time Frame: through study completion, an average of 9 months
Diabetic neuropathy severity assessment using The Composite Autonomic Symptom Score-31, overall score.
through study completion, an average of 9 months
Diabetic neuropathy quality of life evaluation using Euro quality of life -5 dimensions -5 levels scale.
Time Frame: through study completion, an average of 9 months.
Diabetic neuropathy quality of life evaluation using EuroQOL-5D-5L index value.
through study completion, an average of 9 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2023

Primary Completion (Actual)

June 30, 2023

Study Completion (Actual)

January 22, 2024

Study Registration Dates

First Submitted

May 21, 2023

First Submitted That Met QC Criteria

August 13, 2023

First Posted (Actual)

August 15, 2023

Study Record Updates

Last Update Posted (Actual)

April 10, 2024

Last Update Submitted That Met QC Criteria

April 8, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 34059/8/20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diabetic Neuropathies

Clinical Trials on Clinical Evaluation/Questionnaires

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe