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

Exclusion Criteria

• •Lack of suitability for the trial:
• •1. 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.
• •2. Neuropathy of any cause other than diabetes mellitus which might interfere with the assessment of the severity of dPNP.
• •3. Other neurologic diseases that may produce weakness, sensory loss, or autonomic symptoms or test abnormality.
• •4. Myopathy of any cause.
• •5. Peripheral vascular disease severe enough to cause intermittent claudication or ischemic ulcers or limb ischemia.
• •6. Patients with proliferating retinopathy requiring immediately therapy and impending blindness.
• •7. Psychiatric, psychological, or behavioural symptoms that would interfere with the patient's ability to participate in the trial.
• •8. Patients with any active neoplastic disease except basal cell carcinoma.
• •9. Patients with atrial fibrillation unless controlled and stabilised by medication.
• •10. 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.
• •11. Patients who have had organ transplants of any kind.
• •12. 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).
• •13. Patients with a recent history (within last 12 months) of drug or alcohol abuse.
• •14. Use of any investigational drug (participation in a clinical trial) within last 1 month.
• •15. History of severe or anaphylactic reaction to drugs, sulfur or biologic products.
• •16. Recent (within last 3 months) ketoacidosis or hypoglycaemia, necessitating hospital admission.
• •17. Antioxidant therapy (vitamins E \> 400 IU, C \> 200 mg, and beta-Carotene \> 30 mg) or pentoxyphylline within last 1 month before start of trial.
• •18. Use of thioctic acid (\> 50 mg), evening primrose oil or any other gamma-linolenic acid containing substance within the last 3 months.
• •19. Continued use of medications listed in section 6.2.3.
• •20. Bilateral sural nerve biopsies.
• •21. Existing foot ulcers.
• •Safety concerns:
• •22. 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.
• •23. History of allergic reaction to the study medication or its excipients.
• •Administrative reasons:
• •24. Informed Consent is not signed or the patient has not complete competence to co-operate.
• •25. Any language barriers that can affect adequate understanding.
• •26. Anticipated non-availability for study visits/procedures.
• •27. Vulnerable subjects (such as persons kept in detention)