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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
90
oral dispersible tablet with vitamin B12 1000mcg
Placebo tablet
University General Hospital AHEPA
Thessaloniki, Thessaloniki, Greece
Change in Sural Nerve Function measured by conduction velocity
Sural Nerve conduction velocity measured as m/s
Time frame: 12 months
Change in Sural Nerve Function measured by amplitude
Sural Nerve conduction amplitude measured as μV
Time frame: 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.
Time frame: 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. )
Time frame: 12 months
Change in Electrochemical Skin Conductance
Electrochemical Skin Conductance in hands and feet measured by SUDOSCAN
Time frame: 12 months
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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)
Time frame: 12 months
Change in Vibration perception threshold
Vibration perception threshold was measured using a Biothesiometer
Time frame: 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.
Time frame: 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)
Time frame: 12 months
serum vitamin B12 levels
serum vitamin B12 levels
Time frame: 12 months
Adverse events
report of any adverse events
Time frame: 12 months