Randomized double-blind, placebo-controlled parallel group study over 12 months to assess the effects of treatment with benfotiamine on morphometric, neurophysiological, and clinical measures in type 2 diabetes patients with mild to moderate symptomatic polyneuropathy
- Conditions
- G63.2Diabetic polyneuropathy
- Registration Number
- DRKS00014832
- Lead Sponsor
- WÖRWAG Pharma GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 57
• Informed consent signed and dated
• Diabetes mellitus type 2 according to the American Diabetes Association criteria (2017), lasting =1 year
• Stable diabetes metabolism, defined as no metabolic decompensation within the last 3 months (severe hypoglycemia with unconsciousness, ketoacidosis)
• According to the investigator’s opinion no further optimizing potential in diabetic control
• Age: =18 years
• Neuropathic symptoms =6 months
• Presence of mild to moderate diabetic sensorimotor polyneuropathy (DSPN) with Neuropathy Disability Score (NDS) 3-8 points confirmed by at least one of the following: reduced sural sensory nerve conduction velocity (SNCV), sural sensory nerve action potential (SNAP), peroneal motor nerve conduction velocity (MNCV), tibial MNCV
• Measurable sural SNCV, peroneal MNCV or tibial MNCV above detection limit
• CNFL <1SD below the mean of control subjects
• At least 1 palpable pulse of posterior tibial artery or dorsal artery on each side of the foot
• Stable diabetes medication without optimizing potential
• Stable insulin dose for insulin-dependent patients within the last 3 months
• HbA 1c <9.5%
• Acceptable contraceptive measures with female patients in childbearing potential
Ability to meet the study center visits for the study duration
• Subjects with secondary forms of diabetes such as due to pancreatitis
• Contraindications, known allergy, or hypersensitivity to benfotiamine or other ingredients of the study medication or local anesthetics
• Neuropathy of any cause other than diabetes which might interfere with neurological assessment
• Severe pain other than of neuropathic origin that might impair the assessment of neuropathic pain
• Diseases with mixed pain components
• Pain level >9 over 24 h on a numerical 11-Point rating scale
• Proximal asymmetric neuropathy or neuropathic symptoms of the trunk or proximal lower limbs
• Foot ulcer or infection
• 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)
• Peripheral arterial occlusive disease Fontaine stage II-IV
• Neoplasms
• Chronic kidney disease with severely decreased estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m² at screening using the simplified modification of diet in renal disease (MDRD) equation• 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)
• Uncontrolled high blood pressure (DBP >95 mmHg and/or SBP >160 mmHg), unless clearly documented to be white-coat hypertension
• 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, except for a mild rise in bilirubin considered to be due to Gilbert’s condition.
• Generalized immune diseases (e.g. HIV-positive, autoimmune diseases, connective tissue diseases)
• Endocrine diseases like hyper- or hypothyroidism
• Treatment, lasting at least 5 days or longer, with alpha-lipoic acid, B-vitamins, evening
primrose oil, or deproteinized hemoderivates of calf blood, containing low-molecular
weight compounds of up to 5.000 Da or with other substances with interaction to the study
product (e.g. 5-fluorouracil) or affecting study endpoints within the last 3 months before
screening, except for daily intake of B-vitamins amounting to less than 1500 % of the
recommended daily allowance (RDA) lasting until one month prior to screening.
• Treatment with cutaneous electrical nerve stimulation, muscle stimulation or acupuncture within the last month
• Treatment of neuropathic pain with antidepressants, anticonvulsants, sodium channel blockers, opioids, neuroleptics, and capsaicin 8% patch within the last 3 months prior to screening, except for a monotherapy with Gabapentin, Pregabalin or Duloxetin without
relevant dose change within the last 2 months prior to screening and during the study
• Mental, psychiatric or other conditions compromising data collection and understanding of written or oral instructions during the study
• Present or previous chronic alcohol abuse and/or abuse of other drugs
• Pregnant women or nursing mothers
• Participation in another clinical trial study within the last 3 months
• Ability and willingness to abstain from alcohol and from engaging in strenuous physical activity from
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Corneal confocal microscopy (CCM): corneal nerve fiber length (CNFL) (Baseline and after 6 and 12 months)
- Secondary Outcome Measures
Name Time Method