- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00328601
Assessment of Efficacy and Safety of Thioctic Acid in the Oral Treatment of Symptomatic Diabetic Neuropathy (SYDNEY 2)
Assessment of Efficacy and Safety of Thioctic Acid in the Oral Treatment of Symptomatic Diabetic Neuropathy (SYDNEY 2) Randomised, Double-blind,Placebo-controlled Multicentre Trial With 4 Parallel Groups
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.
Study Overview
Detailed Description
Study Type
Enrollment
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Holon, Israel, 58100
- Wolfson Medical Center, Diabetes Unit
-
Jerusalem, Israel, 91120
- Haddassah Medical Center Ein Kerem, Diabetes Unit
-
-
-
-
-
Moscow, Russian Federation, 119048
- Chair of Nervous Diseases of IM Sechenov Moscow Medical Academy at City Clinical Hospital
-
Moscow, Russian Federation, 125315
- Chair of Endocrinology and Diabetology of Russian Medical Academy of Postgraduate Education at Central Clinical Hospital of Ministry of Communication RF
-
Moscow, Russian Federation, 127486
- Federal Centre of Medical Social Expertise and Rehabilitation of Invalids, Centre Diabetic Food
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Dan Ziegler, Prof., German Diabetes Research Institute, Heinrich Heine University, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany
Publications and helpful links
General Publications
- Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet. 1993 May 22;341(8856):1306-9. doi: 10.1016/0140-6736(93)90816-y.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: Diabetes Care. 2003 Jul;26(7):2227.
- 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.
- 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.
- 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.
- 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. Erratum In: BMJ 1999 Jan 2;318(7175):29.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Endocrine System Diseases
- Diabetes Complications
- Diabetes Mellitus
- Neuromuscular Diseases
- Peripheral Nervous System Diseases
- Polyneuropathies
- Diabetic Neuropathies
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Micronutrients
- Vitamins
- Antioxidants
- Vitamin B Complex
- Thioctic Acid
Other Study ID Numbers
- D-20557-3258
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diabetic Polyneuropathy
-
Eva PharmaMARC-CRORecruiting
-
Imperial College LondonActegy Ltd.Not yet recruitingDiabetic Neuropathies | Diabetic Peripheral Neuropathy | Diabetic Polyneuropathy | Diabetic ComplicationUnited Kingdom
-
Ilko Ilac San. ve Tic. A.S.CompletedPeripheral (Sensorimotor) Diabetic Polyneuropathy
-
Mundipharma Research GmbH & Co KGCompletedModerate to Severe Pain Due to Diabetic PolyneuropathyGermany
-
Maastricht University Medical CenterZonMw: The Netherlands Organisation for Health Research and DevelopmentCompletedDiabetic Patients With PolyneuropathyNetherlands
-
NycomedCompletedSymptomatic Diabetic Peripheral PolyneuropathyDenmark
-
Timothy J. Best Medicine Professional CorporationThe Physicians' Services Incorporated FoundationCompleted
-
Eisai Inc.CompletedMild to Moderate Diabetic Sensorimotor PolyneuropathyUnited States
-
Eastern Virginia Medical SchoolNational Institutes of Health (NIH)CompletedDiabetic; Neuropathic, Polyneuropathy (Manifestation)United States
-
AbbVie (prior sponsor, Abbott)CompletedDiabetic Neuropathies | Diabetic Neuropathy, Painful | Diabetic Polyneuropathy | Diabetic Neuralgia | Neuralgia, DiabeticUnited States, Canada, France, Germany, Italy, Mexico, Puerto Rico
Clinical Trials on Thioctic Acid
-
Seoul St. Mary's HospitalGlaxoSmithKlineTerminatedNASH (Non-alcoholic Steato-hepatitis)
-
Chonbuk National University HospitalCompletedDiabetic NeuropathyKorea, Republic of
-
Oregon State UniversityOregon Health and Science University; National Center for Complementary and...Active, not recruiting
-
University of PennsylvaniaCompleted
-
National Center for Research Resources (NCRR)University of RochesterCompletedMitochondrial Myopathy
-
Oregon Health and Science UniversityCompletedTreated HypertensionUnited States
-
Universidad Popular Autónoma del Estado de PueblaCompletedDiabetic Neuropathy
-
Ain Shams UniversityCompletedCesarean Section; Dehiscence | Cesarean Scar NicheEgypt
-
Tanta UniversityNot yet recruitingDiabetes MellitusType 1