Effects of benfotiamine treatment over 12 months on variables of peripheral diabetic neuropathy

Phase 1

• Conditions: Diabetic neuropathy; MedDRA version: 14.1Level: LLTClassification code 10036113Term: Polyneuropathy in diabetesSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2013-001058-85-DE
• Lead Sponsor: Wörwag Pharma GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-03
• Last Update Posted: 29 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Signed and dated written informed consent obtained before any study-related activities
2.Have type 1 or type 2 diabetes mellitus based on the disease diagnostic criteria (WHO) classification on ongoing insulin or/and oral antidiabetic therapy with a stable regimen for the previous 3 months
3.Male or female subjects aged between 18 and 75 years, inclusive
4.Have an HbA1c level = 9.5% without optimizing potential
5.(mTCNS = (above or equal to) 6) OR (a score on the MNSI questionnaire of =4 or a score on the MNSI examination =2.5)
6.Medical history without major pathology (with the exception of type 2 diabetes) as judged by the investigator, especially no major peripheral artery disease.
7.Body mass index (BMI) between 25 and 45kg/m2, both inclusive
8.Ability and willingness to abstain from alcohol and from engaging in strenuous physical activity from 24 hours prior to each visit until discharge from the unit.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 11
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion Criteria

1.Subjects with secondary forms of diabetes such as due to pancreatitis.
2.Current or previous treatment (less than 6 months) with benfotiamine, B-vitamins, vitamin B complex, alpha lipoic acid or actovegin.
3.Have any contraindications, known allergy, or hypersensitivity to benfotiamine.
4.Have any contraindications, known allergy, or hypersensitivity to local anesthetics.
5.Neuropathy by other origin than diabetes.
6.Other severe pain that might impair the assessment of neuropathic pain.
7.Treatment with more than one of following: tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsants, class I antiarrhythmics with Na-channel inhibition (mexiletine, flecainid, propafenon and others) or neuroleptics in patients receiving these drugs for neuropathic pain.
8.Have participated in an interventional medical, surgical, or pharmaceutical study within the last three months prior to entry into the study.
9.Women of child-bearing age who are pregnant, lactating or plan a pregnancy within the next 24 months.
10.Patients on systemic glucocorticoid treatment (except topic or inhalative preparations) within the last 3 months prior to screening.
11.Subjects with any severe medical or surgical history of conditions likely to confound study assessments or study endpoints, for example but not limited to haemoglobinopathies, inflammatory bowel disease, cystic fibrosis, bariatric surgery and/or any surgery shortening the intestine, history of galactose intolerance, lactose- or glucose-galactose-malabsorption.
12.Subjects with a suspicion for malignant diseases or a history of a malignant disease within the last 10 years.
13.As judged by the investigator, serious and/or unstable coronary heart disease (unstable angina, myocardial infarction within the preceding 6 months), congestive heart failure of New York Heart Association Class III or worse, uncontrolled hypertension, history of congenital QT-syndrome within family, history of stroke (within the preceding 6 months) or serious peripheral vascular disease.
14.Clinically significant vital signs including known bradycardia with pulse rate < 50/min.
15.Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the Investigator.
16.Clinical or laboratory evidence of hepatic dysfunction or disease; laboratory evidence defined as any of the following parameters: alkaline phosphatase, ALT, AST or bilirubin > 3x ULN. Isolated mild rise in bilirubin considered to be due to Gilbert’s condition is allowed.
17.Chronic pancreatitis.
18.Uncontrolled high blood pressure (DBP > 95 mmHg and/or SBP > 160 mmHg), unless clearly documented to be white-coat hypertension
19.History of any psychiatric condition that might impair the subject’s ability to understand or to comply with the requirements of the study or to provide informed consent.
20.Currently active or history of alcohol abuse (defined as an intake of more than 24 units of alcohol per week; one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits) or drug addiction (including soft drugs like cannabis products).
21.Use of concomitant medication which would be likely to interact with benfotiamine (according to the subject information leaflet).
22.Subjects known to be positive for Hepatitis B surface antigen or Hepatitis C antibodies (or diagnosed with active hepatitis according to local

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The aim of the present study is to assess before, as well as 6 and 12 months following a therapy with benfotiamine the influence of therapy on intraepidermal nerve fiber density (an early marker of nerve damage) in 22 people with type 1 or 2 diabetes mellitus and diabetic sensorimotor polyneuropathy.;Secondary Objective: To investigate the effects of therapy on skin autofluorescence (a measure of accumulation of toxic compounds), as well as on neuropathic symptoms and deficits.;Primary end point(s): Change from baseline in intraepidermal nerve fiber density (IENFD) after 6 months of benfotiamine treatment compared to placebo.<br><br>Change from baseline in IENFD after 12 months of benfotiamine treatment compared to placebo.<br>;Timepoint(s) of evaluation of this end point: Baseline, 6 months, 12 months.