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Diabetic PolyneuropathyPhase 3NATHAN1NCT00977483

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

A Phase 3 study testing Thioctic Acid in people with Diabetic Polyneuropathy, run by MEDA Pharma GmbH & Co. KG at 38 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Diabetic Polyneuropathy
What is being tested?
Thioctic Acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
460 participants
Where
38 sitesin 9 countries
Study dates
May 1998to Jan 2005
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Signed Informed Consent. Patients must have willingness and complete competence to cooperate and language barriers must not preclude adequate understanding
  • Diabetes mellitus (Type I or II), as defined by the American Diabetes Association 1997, lasting > 1 year
  • 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)
  • 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
  • Severity of diabetic polyneuropathy must be Stage 1 or 2a
  • 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%)
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  • NIS[LL]+7 tests ≥ 97.5 percentiles (corresponding to 4.43 transformed score points)
  • NIS[LL] ≥ 2 points (NIS[LL] is based on questions 17-24, 28, 29, 34, 35, and 37 of the NIS)
  • 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
  • TSS (feet) ≤5
  • 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

Who cannot join

  • 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
  • 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
  • Peripheral vascular disease severe enough to cause intermittent claudication or ischemic ulcers or limb ischemia
  • Patients with a history of ophthalmological findings suggesting a high risk for visual loss i.e., significant maculopathy or proliferative retinopathy
  • 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
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  • Patients with atrial fibrillation unless controlled and stabilised by medication (changed to this criterion by Amendment 1)
  • 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
  • Patients who have had organ transplants of any kind
  • 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)
  • Patients with a recent history (within last 12 months) of drug or alcohol abuse
  • Use of any investigational drug within the last 6 months
  • History of severe or anaphylactic reaction to multiple drugs, sulfur products, or biologic products (changed to this criterion by Amendment 1)
  • Ketoacidosis or hypoglycaemia within last 3 months resulting in hospital admission
  • Antioxidant therapy (vitamins E > 400IU, C > 200mg, and beta-Carotene > 30mg) or pentoxyphylline within last 1 month before start of trial
  • Use of evening primrose oil or any other gamma-linolenic acid containing substance within the last 3 months
  • Use of thioctic acid > 50mg/day within last 3 months
  • 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
  • Bilateral sural nerve biopsies
  • Existing foot ulcers
  • Pregnant or lactating females
  • Continued use of medications listed in protocol 6.3.3 (first paragraph)
  • Medication non-compliance (deviation of more than ±10% of dosages to be taken (1 tablet/day))

Trial locations and contacts

38 sites in 9 countries.

38 sites in 9 countries

United States25 sites

  • Lovelace Scientific Resources, Inc.

    Albuquerque, New Mexico, 87108

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48019-0205

  • ´Diabetes Care Center

    Birmingham, Alabama, 35205

  • Beth Israel Medical Center

    Boston, Massachusetts, 02215

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Missouri Dept. of Neurology

    Columbia, Missouri, 65212

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Dallas Diabetes & Endocrine Center

    Dallas, Texas, 75230

  • University of Texas South Western Medical Center

    Dallas, Texas, 75325-8858

  • City of Hope National Medical Center

    Duarte, California, 91010

  • East Carolina University, School of Medicine

    Greenville, North Carolina, 27858

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Medical Building

    Long Beach, California, 90805

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Health Partners Riverside Neurology Clinic

    Minneapolis, Minnesota, 55454-1478

  • Ney York Hospital Cornell Med Center

    New York, New York, 10021

  • Leonard R. Strelitz Diabetes Institutes

    Norfolk, Virginia, 23510

  • Creighton University Diabetes Center

    Omaha, Nebraska, 68131

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Diabetes & Glandular Disease Center

    San Antonio, Texas, 78229-3894

  • UCSD Neuromuscular Research Program

    San Diego, California, 92103

  • University of California

    San Francisco, California, 94143-0114

  • Mayo Clinic Arizona

    Scottsdale, Arizona, 85259

  • Diabetes Research Center

    Tustin, California, 92780

Other trials in United States

Italy3 sites

  • Policlinic University

    Naples, 80138

  • Hospital Geriatrico Diabetological Service

    Padova, 35137

  • Hosptal of Parma Department of Medicine

    Parma, 43100

Other trials in Italy

Spain3 sites

  • Hospital del Mar Department Neurophysiology

    Barcelona, 08003

  • Hospital Clinico y Provincial

    Barcelona, 08036

  • C.H.U.S. General Hospital

    Santiago de Compostela, 15705

Other trials in Spain

Croatia2 sites

  • University Clinic for Diabetes, Endocrinology and Metabolic

    Zagreb, 10000

  • University Clinic of Internal Medicine

    Zagreb, 10000

Other trials in Croatia

Denmark1 site

  • University Hospital

    Hvidovre, 2650

Other trials in Denmark

France1 site

  • Hospital Jean Verdler

    Bondy, 93143

Other trials in France

Netherlands1 site

  • University Hospital Utrecht Department of Internal Medicine

    Utrecht, 3584

Other trials in Netherlands

Sweden1 site

  • University Clinic

    Malmö, 20602

Other trials in Sweden

United Kingdom1 site

  • Manchester Royal Infirmary Department of Medicine

    Manchester, M13 9WL

Other trials in United Kingdom

About this study

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

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

Read the 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.

Being tested
Thioctic Acid, Placebo
Medical subject headings
Diabetic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Thioctic AcidDrug

    Also called alpha-lipocic acid

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

  • PlaceboDrug

    1 tablet once daily 4 years double-blind treatment period

Study groups in NCT00977483
Study groupRoleWhat they receive
Drug: Thioctic AcidExperimental600mg tablet Thioctic Acid (alpha-lipoic acid) once daily throughout the trial
Receives: Drug: Thioctic Acid
Drug: PlaceboPlacebo comparator1 tablet once daily throughout the trial
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 4 years

Secondary outcomes (1)

  1. 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.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Sep 2009 (estimated)
  2. Study startMay 1998
  3. Primary completionJan 2005
  4. Study completionJan 2005

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
460 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00977483
Sponsor's protocol ID
D-20557-3011
Other IDs
NATHAN1, D-20557/9353000001
Acronym
NATHAN1
Status last verified
Nov 2016
First submitted
14 Sep 2009
Last updated
7 Feb 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21775755

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Thioctic Acid in people with Diabetic Polyneuropathy, run by MEDA Pharma GmbH & Co. KG at 38 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Italy, Spain, Croatia, Denmark and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00977483, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2022.

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