Assessment of Efficacy and Safety of Thioctic Acid in the Oral Treatment of Symptomatic Diabetic Neuropathy (SYDNEY 2)

Following a screening visit, patients will receive placebo oral for 7 days. Eligible patients with chronic symptoms will then randomly be assigned to one of 4 treatment groups and treated with trial medication for 5 weeks.

Inclusion criteria

• Diabetes mellitus (Type I or II), as defined by the American Diabetes Association, 1997, lasting 1 year.
• Patient must have a symmetric sensory-motor peripheral polyneuropathy of at least stage 2 attributable to diabetes mellitus following a thorough evaluation for other causes of neuropathy.
• HbA1C < 10%.
• TSS > 7.5 points.
• NISLL > 2 points.
• Pain sensation (according to pin-prick sensitivity test) absent or decreased (NIS item 35 1).
• Age range: 18 to 74 years. Inclusion criteria prior to randomisation
• The TSS must be > 5 points
• The TSS range (maximum TSS minus minimum TSS during the run-in phase) must be less than 3 points to avoid inclusion of patients with rapidly oscillating symptoms.
• At least 1 of the 4 symptoms of the TSS must have occurred continuously over the last 3 months.
• Lack of compliance, i.e. below 85% or above 115% (Accordingly, 6 daily doses taken of the 7 daily doses scheduled for Phase A would be acceptable).

Exclusion criteria

Lack of suitability for the trial:

• Proximal asymmetric neuropathy, cranial neuropathies, truncal radiculopathy, diabetic plexopathies, or acute or active mononeuropathies (including cranial neuropathies, post-herpes neuralgias, etc.), with the exception of carpal tunnel syndrome (CTS) or tardy ulnar neuropathy (TUN) or both.
• Neuropathy of any cause other than diabetes mellitus which might interfere with the assessment of the severity of dPNP.
• Other neurologic diseases that may produce weakness, sensory loss, or autonomic symptoms or test abnormality.
• Myopathy of any cause.
• Peripheral vascular disease severe enough to cause intermittent claudication or ischemic ulcers or limb ischemia.
• Patients with proliferating retinopathy requiring immediately therapy and impending blindness.
• Psychiatric, psychological, or behavioural symptoms that would interfere with the patient's ability to participate in the trial.
• Patients with any active neoplastic disease except basal cell carcinoma.
• Patients with atrial fibrillation unless controlled and stabilised by medication.
• Patients with clinically significant cardiac, pulmonary, gastrointestinal, haematological, or endocrine disease (other than diabetes) that may confound interpretation of the study results or prevent the patient from completing the study.
• Patients who have had organ transplants of any kind.
• Patients with significant hepatic or renal disease (ASAT, ALAT or GGT >2 times normal, serum creatinine >1.8 mg/dL (>159 mmol/l) for males or >1.6 mg/dL (>141 mmol/l) for females).
• Patients with a recent history (within last 12 months) of drug or alcohol abuse.
• Use of any investigational drug (participation in a clinical trial) within last 1 month.
• History of severe or anaphylactic reaction to drugs, sulfur or biologic products.
• Recent (within last 3 months) ketoacidosis or hypoglycaemia, necessitating hospital admission.
• Antioxidant therapy (vitamins E > 400 IU, C > 200 mg, and beta-Carotene > 30 mg) or pentoxyphylline within last 1 month before start of trial.
• Use of thioctic acid (> 50 mg), evening primrose oil or any other gamma-linolenic acid containing substance within the last 3 months.
• Continued use of medications listed in section 6.2.3.
• Bilateral sural nerve biopsies.
• Existing foot ulcers.

Safety concerns:

• Pregnant or lactating females: Pregnancy as evidenced by positive b-hCG-test at screening visit or by testing performed at the study site on demand, or women of child-bearing potential not using adequate contraception.
• History of allergic reaction to the study medication or its excipients.

Administrative reasons:

• Informed Consent is not signed or the patient has not complete competence to co-operate.
• Any language barriers that can affect adequate understanding.
• Anticipated non-availability for study visits/procedures.
• Vulnerable subjects (such as persons kept in detention)