Clinical trial NCT04706377: Vitamin B12 Supplementation in Diabetic Neuropathy
Official title: Vitamin B12 Supplementation in Diabetic Neuropathy :1-year Double Blind Randomized Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
Collaborators: name: University of Sheffield
name: University Hospital Tuebingen
First posted: 2021-01-12
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double Blind Placebo Controlled Randomized Clinical Trial
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Sural Nerve Function measured by conduction velocity
timeFrame: 12 months
measure: Change in Sural Nerve Function measured by amplitude
timeFrame: 12 months
measure: Change in Michigan Neuropathy Screening Instrument Questionnaire
timeFrame: 12 months
measure: Change in Michigan Neuropathy Screening Instrument Examination
timeFrame: 12 months
measure: Change in Electrochemical Skin Conductance
timeFrame: 12 months
measure: Change in Cardiovascular Autonomic Reflex Tests (CARTs)
timeFrame: 12 months
measure: Change in Vibration perception threshold
timeFrame: 12 months
measure: Change in level of pain with painDETECT questionnaire
timeFrame: 12 months
measure: Change in quality of life score
timeFrame: 12 months
measure: serum vitamin B12 levels
timeFrame: 12 months
Secondary outcomes:
measure: Adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: Thessaloníki
country: Greece
facility: University General Hospital AHEPA
state: Thessaloniki
Study officials:
References: