Assessment of Efficacy and Safety of Thioctic Acid in the Oral Treatment of Diabetic Polyneuropathy (Stage 1 or 2) (NATHAN1)

This study has been completed.
Sponsor:
Collaborators:
Clinquest, Inc.
Ergomed
Quintiles
Information provided by:
MEDA Pharma GmbH & Co. KG
ClinicalTrials.gov Identifier:
NCT00977483
First received: September 14, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  Purpose

The purpose of this study is to assess clinical efficacy and safety of long-term orally administered thioctic acid in the treatment of diabetic polyneuropathy.


Condition Intervention Phase
Diabetic Polyneuropathy
Drug: Thioctic Acid (alpha-lipocic acid)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Assessment of Efficacy and Safety of Thioctic Acid in the Oral Treatment of Diabetic Polyneuropathy (Stage 1 or 2) NATHAN1 A Randomized, Placebo-controlled, Double-blind Multi-centre Trial With 2 Parallel Groups

Resource links provided by NLM:


Further study details as provided by MEDA Pharma GmbH & Co. KG:

Primary Outcome Measures:
  • Primary efficacy variable: Absolute change in the neuropathy impairment score lower limbs enlarged by 7 objective items (NISLL+7) between baseline (mean of Visit 0.3 and 0.4 or last available value before randomisation, respectively) and endpoint [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • NIS, NSC, TSS, LLF, QST, VDT, CDT and HP, QAE by means of the HRDB, amplitude CMAP, DL and MNCV on peroneal and tibial nerves, amplitude SNAP and latency on sural nerve, foot inspection, efficacy. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Enrollment: 460
Study Start Date: May 1998
Study Completion Date: January 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug: Thioctic Acid
600mg tablet Thioctic Acid (alpha-lipoic acid) once daily throughout the trial
Drug: Thioctic Acid (alpha-lipocic acid)
600mg tablet once daily 4 years double-blind treatment period
Placebo Comparator: Drug: Placebo
1 tablet once daily throughout the trial
Drug: Placebo
1 tablet once daily 4 years double-blind treatment period

Detailed Description:

Stage 1 or 2a diabetic (poly)neuropathy (DNP) (Appendix 3) in patients with diabetes mellitus (type I or II); neuropathy impairment score of the lower limbs, enlarged by 7 objective items (NISLL+7) ≥ 97.5 percentile (corresponding to 4.43 score points); total symptoms score of the feet (TSSfeet) ≤ 5.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed Informed Consent. Patients must have willingness and complete competence to cooperate and language barriers must not preclude adequate understanding
  2. Diabetes mellitus (Type I or II), as defined by the American Diabetes Association 1997, lasting > 1 year
  3. Males or females 18 to 64 years (older patients are excluded because of age-related changes in reflexes, quantitative sensory testing endpoints, and nerve conduction endpoints)
  4. Patient must have a symmetric sensory-motor peripheral polyneuropathy attributable to diabetes mellitus following a thorough evaluation for other causes of neuropathy determined by performing complete medical and neurological examinations including physical and neurological history, history of medications, history of exposure to other toxins, and laboratory studies
  5. Severity of diabetic polyneuropathy must be Stage 1 or 2a
  6. Insulin regimen, weight, diet, and activity level must be relatively stable in the opinion of the investigator (for example, HbA1C must not vary by more than ± 2 Vol.% within 6 months preceding the study i.e. if the index measure = 10% the range would be 8-12%)
  7. NIS[LL]+7 tests ≥ 97.5 percentiles (corresponding to 4.43 transformed score points)
  8. NIS[LL] ≥ 2 points (NIS[LL] is based on questions 17-24, 28, 29, 34, 35, and 37 of the NIS)
  9. One of the following:

    • an abnormality of nerve conduction attributes in two separate nerves, i.e. ≥99th percentile for DL or ≤1st percentile for NCV or amplitude or
    • an abnormality of HRDB, i.e. ≤ 1st percentile
  10. TSS (feet) ≤5
  11. Females must either be surgically sterilised (tubal ligation, bilateral oophorectomy, or hysterectomy) or at least 1 year postmenopausal or practicing an acceptable method of contraception, including oral contraceptives with a stable regimen for at least two months, depo-medroxyprogesterone, a barrier method alone (diaphragm, condoms, or contraceptive sponge with spermicidals), or an IUD that has been in place for at least two months

Exclusion Criteria:

  1. Patients with proximal asymmetric neuropathy, cranial neuropathies, truncal radiculopathy, pan dysautonomia, diabetic plexopathies, or acute or active mononeuropathies (including cranial neuropathies, post-herpetic neuralgias, etc.), the presence of which might obscure accurate assessment of severity of the diabetic polyneuropathy under assessment, 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 Other neurologic diseases that may produce weakness, sensory loss, or autonomic symptoms or test abnormality which might interfere with the assessment of the severity of dPNP Myopathy of any cause which might interfere with the assessment of the severity of dPNP
  3. Peripheral vascular disease severe enough to cause intermittent claudication or ischemic ulcers or limb ischemia
  4. Patients with a history of ophthalmological findings suggesting a high risk for visual loss i.e., significant maculopathy or proliferative retinopathy
  5. Psychiatric, psychological, or behavioural symptoms that would interfere with the patient's ability to participate in the trial
  6. Patients with any active neoplastic disease except basal cell carcinoma
  7. Patients with atrial fibrillation unless controlled and stabilised by medication (changed to this criterion by Amendment 1)
  8. Patients with clinically significant cardiac, pulmonary, gastrointestinal, hematologic, or endocrine disease (other than diabetes) that may confound interpretation of the study results or prevent the patient from completing the study
  9. Patients who have had organ transplants of any kind
  10. Patients with significant hepatic or renal disease (ASAT or ALAT >2 times normal, serum creatinine >1.8 mg/dL (>159 µmol/l) for males or >1.6 mg/dL (>141 µmol/l) for females)
  11. Patients with a recent history (within last 12 months) of drug or alcohol abuse
  12. Use of any investigational drug within the last 6 months
  13. History of severe or anaphylactic reaction to multiple drugs, sulfur products, or biologic products (changed to this criterion by Amendment 1)
  14. Ketoacidosis or hypoglycaemia within last 3 months resulting in hospital admission
  15. Antioxidant therapy (vitamins E > 400IU, C > 200mg, and beta-Carotene > 30mg) or pentoxyphylline within last 1 month before start of trial
  16. Use of evening primrose oil or any other gamma-linolenic acid containing substance within the last 3 months
  17. Use of thioctic acid > 50mg/day within last 3 months
  18. History of use of medications or vitamins known to cause peripheral neuropathy including but not limited to use of phenytoin or carbamazepine over 15 or more years, or use of pyridoxine > 100mg/d within the past 12 months
  19. Bilateral sural nerve biopsies
  20. Existing foot ulcers
  21. Pregnant or lactating females
  22. Continued use of medications listed in protocol 6.3.3 (first paragraph)
  23. Medication non-compliance (deviation of more than ±10% of dosages to be taken (1 tablet/day))
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00977483

  Hide Study Locations
Locations
United States, Alabama
´Diabetes Care Center
Birmingham, Alabama, United States, 35205
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
Medical Building
Long Beach, California, United States, 90805
UCSD Neuromuscular Research Program
San Diego, California, United States, 92103
University of California
San Francisco, California, United States, 94143-0114
Diabetes Research Center
Tustin, California, United States, 92780
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Massachusetts
Beth Israel Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48019-0205
United States, Minnesota
Health Partners Riverside Neurology Clinic
Minneapolis, Minnesota, United States, 55454-1478
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
University of Missouri Dept. of Neurology
Columbia, Missouri, United States, 65212
United States, Nebraska
Creighton University Diabetes Center
Omaha, Nebraska, United States, 68131
United States, New Mexico
Lovelace Scientific Resources, Inc.
Albuquerque, New Mexico, United States, 87108
United States, New York
Ney York Hospital Cornell Med Center
New York, New York, United States, 10021
United States, North Carolina
East Carolina University, School of Medicine
Greenville, North Carolina, United States, 27858
United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas South Western Medical Center
Dallas, Texas, United States, 75325-8858
Dallas Diabetes & Endocrine Center
Dallas, Texas, United States, 75230
Baylor College of Medicine
Houston, Texas, United States, 77030
Diabetes & Glandular Disease Center
San Antonio, Texas, United States, 78229-3894
United States, Virginia
Leonard R. Strelitz Diabetes Institutes
Norfolk, Virginia, United States, 23510
Croatia
University Clinic for Diabetes, Endocrinology and Metabolic
Zagreb, Croatia, 10000
University Clinic of Internal Medicine
Zagreb, Croatia, 10000
Denmark
University Hospital
Hvidovre, Denmark, 2650
France
Hospital Jean Verdler
Bondy Cedex, France, 93143
Italy
Policlinic University
Napoli, Italy, 80138
Hospital Geriatrico Diabetological Service
Padova, Italy, 35137
Hosptal of Parma Department of Medicine
Parma, Italy, 43100
Netherlands
University Hospital Utrecht Department of Internal Medicine
Utrecht, Netherlands, 3584
Spain
Hospital del Mar Department Neurophysiology
Barcelona, Spain, 08003
Hospital Clinico y Provincial
Barcelona, Spain, 08036
C.H.U.S. General Hospital
Santiago de Compostela, Spain, 15705
Sweden
University Clinic
Malmö, Sweden, 20602
United Kingdom
Manchester Royal Infirmary Department of Medicine
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
MEDA Pharma GmbH & Co. KG
Clinquest, Inc.
Ergomed
Quintiles
Investigators
Principal Investigator: Peter James Dyck Mayo Clinic, Dept. of Neurology, 200 First Street Southwest, Rochester, MN 55905, USA
  More Information

No publications provided by MEDA Pharma GmbH & Co. KG

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Joachim Maus, MEDA Pharma GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT00977483     History of Changes
Other Study ID Numbers: D-20557-3011, NATHAN1, D-20557/9353000001
Study First Received: September 14, 2009
Last Updated: September 14, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Polyneuropathies
Diabetic Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Thioctic Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 29, 2014