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

February 4, 2022 updated by: MEDA Pharma GmbH & Co. KG

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
460

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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))

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Drug: Thioctic Acid
600mg tablet Thioctic Acid (alpha-lipoic acid) once daily throughout the trial
Drug: Thioctic Acid
600mg tablet once daily 4 years double-blind treatment period
Other Names:
  • alpha-lipocic acid
Placebo Comparator: Drug: Placebo
1 tablet once daily throughout the trial
Drug: Placebo
1 tablet once daily 4 years double-blind treatment period

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
4 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MEDA Pharma GmbH & Co. KG

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Quintiles, Inc.
Ergomed
Clinquest, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Peter James Dyck, Mayo Clinic, Dept. of Neurology, 200 First Street Southwest, Rochester, MN 55905, USA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 1998

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2005

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2005

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 15, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 7, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D-20557-3011
  • NATHAN1
  • D-20557/9353000001

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.

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