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

NCT00328601 | Completed Phase 3

• 1 other identifier: D-20557-3258
• Study Type: interventional
• Target: 170
• Locations: 2 countries
• Sites: 5

Brief Summary

The primary objective of the trial is to determine the optimal dose of orally (tablet) administered thioctic acid in the treatment of symptoms of diabetic polyneuropathy (dPNP). It is expected that at least one of the three dosages to be tested (600, 1200, or 1800 mg tablets) of orally administered thioctic acid improves the symptoms of dPNP as compared to placebo. Secondary objectives are evaluations of other variables pertinent to dPNP, safety, and tolerability.

Conditions

Diabetic Polyneuropathy

Interventions

Thioctic Acid DRUG

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• The TSS must be \> 5 points
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• MEDA Pharma GmbH & Co. KG: lead

Study Sites (5)

Wolfson Medical Center, Diabetes Unit

Holon, 58100, Israel

Location

Haddassah Medical Center Ein Kerem, Diabetes Unit

Jerusalem, 91120, Israel

Location

Chair of Nervous Diseases of IM Sechenov Moscow Medical Academy at City Clinical Hospital

Moscow, 119048, Russia

Location

Chair of Endocrinology and Diabetology of Russian Medical Academy of Postgraduate Education at Central Clinical Hospital of Ministry of Communication RF

Moscow, 125315, Russia

Location

Federal Centre of Medical Social Expertise and Rehabilitation of Invalids, Centre Diabetic Food

Moscow, 127486, Russia

Location

Related Publications (19)

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  PMID: 8098449 BACKGROUND

• Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002 Jan 16;287(3):360-72. doi: 10.1001/jama.287.3.360.

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• Collins SL, Moore RA, McQuayHJ, Wiffen P. Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review. J Pain Symptom Manage. 2000 Dec;20(6):449-58. doi: 10.1016/s0885-3924(00)00218-9.

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• Jarvis B, Coukell AJ. Mexiletine. A review of its therapeutic use in painful diabetic neuropathy. Drugs. 1998 Oct;56(4):691-707. doi: 10.2165/00003495-199856040-00016.

  PMID: 9806111 BACKGROUND

• Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging. 1995 Oct;7(4):317-28. doi: 10.2165/00002512-199507040-00007.

  PMID: 8535059 BACKGROUND

• Cameron NE, Cotter MA. The relationship of vascular changes to metabolic factors in diabetes mellitus and their role in the development of peripheral nerve complications. Diabetes Metab Rev. 1994 Oct;10(3):189-224. doi: 10.1002/dmr.5610100302. No abstract available.

  PMID: 7835170 BACKGROUND

• Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 2004 May;11(9):1135-46. doi: 10.2174/0929867043365387.

  PMID: 15134511 BACKGROUND

• Cameron NE, Cotter MA, Archibald V, Dines KC, Maxfield EK. Anti-oxidant and pro-oxidant effects on nerve conduction velocity, endoneurial blood flow and oxygen tension in non-diabetic and streptozotocin-diabetic rats. Diabetologia. 1994 May;37(5):449-59. doi: 10.1007/s001250050131.

  PMID: 8056181 BACKGROUND

• Nagamatsu M, Nickander KK, Schmelzer JD, Raya A, Wittrock DA, Tritschler H, Low PA. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 1995 Aug;18(8):1160-7. doi: 10.2337/diacare.18.8.1160.

  PMID: 7587852 BACKGROUND

• Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia. 1995 Dec;38(12):1425-33. doi: 10.1007/BF00400603.

  PMID: 8786016 BACKGROUND

• Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999 Aug;22(8):1296-301. doi: 10.2337/diacare.22.8.1296.

  PMID: 10480774 BACKGROUND

• Strokov IA, Kozlova NA, Mozolevskii IuV, Miasoedov SP, Iakhno NN. [The efficacy of the intravenous administration of the trometamol salt of thioctic (alpha-lipoic) acid in diabetic neuropathy]. Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(6):18-22. Russian.

  PMID: 10441861 BACKGROUND

• Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O'Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D; SYDNEY Trial Study Group. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003 Mar;26(3):770-6. doi: 10.2337/diacare.26.3.770.

  PMID: 12610036 BACKGROUND

• Ruhnau KJ, Meissner HP, Finn JR, Reljanovic M, Lobisch M, Schutte K, Nehrdich D, Tritschler HJ, Mehnert H, Ziegler D. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999 Dec;16(12):1040-3. doi: 10.1046/j.1464-5491.1999.00190.x.

  PMID: 10656234 BACKGROUND

• Dyck PJ, Kratz KM, Lehman KA, Karnes JL, Melton LJ 3rd, O'Brien PC, Litchy WJ, Windebank AJ, Smith BE, Low PA, et al. The Rochester Diabetic Neuropathy Study: design, criteria for types of neuropathy, selection bias, and reproducibility of neuropathic tests. Neurology. 1991 Jun;41(6):799-807. doi: 10.1212/wnl.41.6.799.

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• Dyck PJ, Karnes JL, O'Brien PC, Litchy WJ, Low PA, Melton LJ 3rd. The Rochester Diabetic Neuropathy Study: reassessment of tests and criteria for diagnosis and staged severity. Neurology. 1992 Jun;42(6):1164-70. doi: 10.1212/wnl.42.6.1164.

  PMID: 1603343 BACKGROUND

• UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998 Sep 12;317(7160):703-13.

  PMID: 9732337 BACKGROUND

• Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Moller W, Tritschler HJ, Mehnert H. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Free Radic Res. 1999 Sep;31(3):171-9. doi: 10.1080/10715769900300721.

  PMID: 10499773 BACKGROUND

• Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz I, Novosadova M, Maus J, Samigullin R. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov;29(11):2365-70. doi: 10.2337/dc06-1216.

  PMID: 17065669 DERIVED

MeSH Terms

Conditions

Diabetic Neuropathies

Interventions

Thioctic Acid

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids

Study Officials

• Dan Ziegler, Prof.

  German Diabetes Research Institute, Heinrich Heine University, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 19, 2006
• First Posted: May 22, 2006
• Study Start: February 1, 2005
• Study Completion: June 1, 2005
• Last Updated: February 7, 2022

Record last verified: 2008-07

Locations

RU (3); IL (2)