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

NCT ID: NCT00977483

Last Updated: 2022-02-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

460 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-05-31

Study Completion Date

2005-01-31

Brief Summary

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To assess clinical efficacy and safety of long-term orally administered thioctic acid in the treatment of diabetic polyneuropathy.

Detailed Description

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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.

Conditions

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Diabetic Polyneuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Drug: Thioctic Acid

600mg tablet Thioctic Acid (alpha-lipoic acid) once daily throughout the trial

Group Type EXPERIMENTAL

Thioctic Acid

Intervention Type DRUG

600mg tablet once daily 4 years double-blind treatment period

Drug: Placebo

1 tablet once daily throughout the trial

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

1 tablet once daily 4 years double-blind treatment period

Interventions

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Thioctic Acid

600mg tablet once daily 4 years double-blind treatment period

Intervention Type DRUG

Placebo

1 tablet once daily 4 years double-blind treatment period

Intervention Type DRUG

Other Intervention Names

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alpha-lipocic acid

Eligibility Criteria

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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))
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Clinquest, Inc.

INDUSTRY

Sponsor Role collaborator

Ergomed

INDUSTRY

Sponsor Role collaborator

Quintiles, Inc.

INDUSTRY

Sponsor Role collaborator

MEDA Pharma GmbH & Co. KG

INDUSTRY

Sponsor Role lead

Responsible Party

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MEDA Pharma GmbH & Co. KG

Principal Investigators

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Peter James Dyck

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic, Dept. of Neurology, 200 First Street Southwest, Rochester, MN 55905, USA

Locations

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´Diabetes Care Center

Birmingham, Alabama, United States

Site Status

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

Medical Building

Long Beach, California, United States

Site Status

UCSD Neuromuscular Research Program

San Diego, California, United States

Site Status

University of California

San Francisco, California, United States

Site Status

Diabetes Research Center

Tustin, California, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Beth Israel Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Health Partners Riverside Neurology Clinic

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status

University of Missouri Dept. of Neurology

Columbia, Missouri, United States

Site Status

Creighton University Diabetes Center

Omaha, Nebraska, United States

Site Status

Lovelace Scientific Resources, Inc.

Albuquerque, New Mexico, United States

Site Status

Ney York Hospital Cornell Med Center

New York, New York, United States

Site Status

East Carolina University, School of Medicine

Greenville, North Carolina, United States

Site Status

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Dallas Diabetes & Endocrine Center

Dallas, Texas, United States

Site Status

University of Texas South Western Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Diabetes & Glandular Disease Center

San Antonio, Texas, United States

Site Status

Leonard R. Strelitz Diabetes Institutes

Norfolk, Virginia, United States

Site Status

University Clinic for Diabetes, Endocrinology and Metabolic

Zagreb, , Croatia

Site Status

University Clinic of Internal Medicine

Zagreb, , Croatia

Site Status

University Hospital

Hvidovre, , Denmark

Site Status

Hospital Jean Verdler

Bondy, , France

Site Status

Policlinic University

Napoli, , Italy

Site Status

Hospital Geriatrico Diabetological Service

Padua, , Italy

Site Status

Hosptal of Parma Department of Medicine

Parma, , Italy

Site Status

University Hospital Utrecht Department of Internal Medicine

Utrecht, , Netherlands

Site Status

Hospital del Mar Department Neurophysiology

Barcelona, , Spain

Site Status

Hospital Clinico y Provincial

Barcelona, , Spain

Site Status

C.H.U.S. General Hospital

Santiago de Compostela, , Spain

Site Status

University Clinic

Malmo, , Sweden

Site Status

Manchester Royal Infirmary Department of Medicine

Manchester, , United Kingdom

Site Status

Countries

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United States Croatia Denmark France Italy Netherlands Spain Sweden United Kingdom

References

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Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schutte K, Dyck PJ. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011 Sep;34(9):2054-60. doi: 10.2337/dc11-0503. Epub 2011 Jul 20.

Reference Type DERIVED
PMID: 21775755 (View on PubMed)

Other Identifiers

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NATHAN1

Identifier Type: -

Identifier Source: secondary_id

D-20557/9353000001

Identifier Type: -

Identifier Source: secondary_id

D-20557-3011

Identifier Type: -

Identifier Source: org_study_id

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