Vitamin B12 Supplementation in Diabetic Neuropathy

NCT04706377 | Completed

• 1 other identifier: No42439
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective double-blind placebo-controlled trial aims to investigate the safety and efficacy of oral dispersible tablet of vitamin B12 for 1 year, in 90 patients with diabetes mellitus type 2 and neuropathy.

Conditions

Diabetes Mellitus; Diabetic Neuropathies; Diabetic Complication; Diabetic Foot

Keywords

diabetic neuropathy; vitamin B12; SUDOSCAN; metformin; diabetic foot; Diabetes Mellitus; autonomic neuropathy; peripheral neuropathy; painful neuropathy

Outcome Measures

Primary Outcomes (10)

• Change in Sural Nerve Function measured by conduction velocity

  Sural Nerve conduction velocity measured as m/s

  12 months

• Change in Sural Nerve Function measured by amplitude

  Sural Nerve conduction amplitude measured as μV

  12 months

• Change in Michigan Neuropathy Screening Instrument Questionnaire

  Michigan Neuropathy Screening Instrument questionnaire (The Michigan Neuropathy Screening Instrument (MNSI) includes two separate assessments, a 15-item self-administered questionnaire and a lower extremity examination. the questionnaire is scored by summing abnormal responses. Responses are added to obtain a total score. 'Yes' responses to questions 1-3, 5-6, 8-9, 11-12, 14-15 are each counted as one point. 'No' responses to questions 7 and 13 each count as one point. Question 4 was considered to be a measure of impaired circulation and question 10 a measure of general asthenia and were not included in the published scoring algorithm. A score of ≥ 7 was considered abnormal.

  12 months

• Change in Michigan Neuropathy Screening Instrument Examination

  Michigan Neuropathy Screening Instrument Examination (The Michigan Neuropathy Screening Instrument (MNSI) includes two separate assessments, a 15-item self-administered questionnaire that is scored by summing abnormal responses, and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes and is scored by assigning points for abnormal findings.A score ≥ 2 was considered abnormal. Abnormality in each item is graded between 0.5 and 1 and at least more than 2 abnormal items are needed to reach the score of neuropathy. )

  12 months

• Change in Electrochemical Skin Conductance

  Electrochemical Skin Conductance in hands and feet measured by SUDOSCAN

  12 months

• Change in Cardiovascular Autonomic Reflex Tests (CARTs)

  CARTs were performed with Autonomic Nervous System Reader and included R-R variation during deep breathing \[Mean Circular Resultant , Valsalva maneuver , 30:15 ratio expressed as postural index, and blood pressure response to standing (orthostatic hypotension)

  12 months

• Change in Vibration perception threshold

  Vibration perception threshold was measured using a Biothesiometer

  12 months

• Change in level of pain with painDETECT questionnaire

  painDETECT questionnaire consists of seven questions that address the quality of neuropathic pain symptoms; it is completed by the patient and no physical examination is required. The first five questions ask about the gradation of pain, scored from 0 to 5 (never = 0, hardly noticed = 1, slightly = 2; moderately = 3, strongly = 4, very strongly = 5). Question 6 asks about the pain course pattern, scored from -1 to 2, depending on which pain course pattern diagram is selected. The final score between -1 and 38, indicates the likelihood of a neuropathic pain component. A score of ≤ 12 indicates that pain is unlikely to have a neuropathic component (\< 15%), while a score of ≥ 19 suggests that pain is likely to have a neuropathic component (\> 90%). A score between these values indicates that the result is uncertain and a more detailed examination is required.

  12 months

• Change in quality of life score

  Diabetes Quality of Life Brief Clinical Inventory (ThE DQOL questionnaire we used is a 15-items, brief-focused version of the Diabetes Quality of Life (DQOL) questionnaire developed in the DCCT and lowest score means worse quality of life whereas higher values indicate better quality of life)

  12 months

• serum vitamin B12 levels

  serum vitamin B12 levels

  12 months

Secondary Outcomes (1)

• Adverse events

  12 months

Study Arms (2)

Active treatment group

ACTIVE COMPARATOR

Patients were given oral dispersible tablet with 1000μg of vitamin B12 daily for 12 months.

Dietary Supplement: B12 fix 1000mcg

Placebo group

PLACEBO COMPARATOR

Patients were given placebo tablet similar to the tablet given to the active group once a day for 12 months.

Other: Placebo

Interventions

B12 fix 1000mcg DIETARY_SUPPLEMENT

oral dispersible tablet with vitamin B12 1000mcg

Also known as: vitamin B12

Active treatment group

Placebo OTHER

Placebo tablet

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adults (\>18 years old) with Diabetes Mellitus 2
• established Diabetic neuropathy, both peripheral and autonomic (Diabetic Peripheral Neuropathy and Diabetic Autonomic Neuropathy). (Diagnosis was made with a)two or more Cardiovascular Autonomic Reflex Tests abnormal, b)abnormal nerve conduction velocity, c)abnormal Michigan Neuropathy Screening Instrument Questionnaire and Michigan Neuropathy Screening Instrument Examination ).
• good glycemic control (HbA1c between 6.5 and 7.5 %), stable in the last year before participating in the study
• metformin treatment for at least 4 years
• low vitamin B12 levels according to suggested normal values for DM2 patients over 60 years old (\<400 pmol/L)

You may not qualify if:

• pernicious anemia,
• alcoholism
• gastrectomy
• gastric bypass surgery
• pancreatic insufficiency
• malabsorption syndromes
• chronic giardiasis
• acute infection in the last 6 months
• cardiovascular event in the last 6 months
• surgery involving small intestine or Human Immunodeficiency Virus infection.
• Patients with estimated Glomerular Filtration Rate \<50 mL/min/1.73m2
• taking multivitamins or B12 supplements in the last 12 months

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• University of Sheffield: collaborator
• University Hospital Tuebingen: collaborator

Study Sites (1)

University General Hospital AHEPA

Thessaloniki, Thessaloniki, 54621, Greece

Location

MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Neuropathies; Diabetes Complications; Diabetic Foot; Peripheral Nervous System Diseases; Neuropathy, Painful

Interventions

Vitamin B 12

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The tablets containing B12 and placebo had a similar appearance and were packed in similar containers. Patients and health care providers did not know what each package contained.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Internal Medicine-Diabetology

Model Details: Double Blind Placebo Controlled Randomized Clinical Trial

Study Record Dates

• First Submitted: January 9, 2021
• First Posted: January 12, 2021
• Study Start: February 1, 2018
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)