Vitamin B12 Supplementation in Diabetic Neuropathy

Diabetes Mellitus Clinical Trial

Official title:

Vitamin B12 Supplementation in Diabetic Neuropathy :1-year Double Blind Randomized Placebo-Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04706377
• Other study ID #: No42439
• Status: Completed
• Phase: N/A
• Start date: February 1, 2018
• Est. completion date: February 28, 2020

Study information

• Verified date: January 2021
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin treatment for at least four years, and both peripheral and autonomic diabetic neuropathy were randomized to an active treatment group (n=44) receiving B12, and a control group (n=46) receiving placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurement of sural nerve conduction velocity and amplitude, vibration perception threshold, and performed cardiovascular autonomic reflex tests (CARTs: Mean Circular Resultant, Valsalva test, postural index and orthostatic hypotension]). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet. The Michigan Neuropathy Screening Instrument Questionnaire and Examination and questionnaires to evaluate quality of life and level of pain were also used.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: February 28, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Diabetes Complications
• Diabetes Mellitus
• Diabetic Complication
• Diabetic Foot
• Diabetic Neuropathies
• Peripheral Nervous System Diseases

Intervention

Dietary Supplement:
• B12 fix 1000mcg
oral dispersible tablet with vitamin B12 1000mcg

Other:
• Placebo
Placebo tablet

Locations

Country	Name	City	State
Greece	University General Hospital AHEPA	Thessaloníki	Thessaloniki

Sponsors (3)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki	University Hospital Tuebingen, University of Sheffield

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Sural Nerve Function measured by conduction velocity	Sural Nerve conduction velocity measured as m/s	12 months
Primary	Change in Sural Nerve Function measured by amplitude	Sural Nerve conduction amplitude measured as µV	12 months
Primary	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
Primary	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
Primary	Change in Electrochemical Skin Conductance	Electrochemical Skin Conductance in hands and feet measured by SUDOSCAN	12 months
Primary	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
Primary	Change in Vibration perception threshold	Vibration perception threshold was measured using a Biothesiometer	12 months
Primary	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
Primary	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
Primary	serum vitamin B12 levels	serum vitamin B12 levels	12 months
Secondary	Adverse events	report of any adverse events	12 months