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The Effect of A-lipoic Acid (ALA) on Fatty Acid-induced Impairment of Glucose-stimulated Insulin Secretion

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01056497
Recruitment Status : Completed
First Posted : January 26, 2010
Last Update Posted : October 2, 2012
Canadian Diabetes Association
Information provided by (Responsible Party):
Gary Lewis, University Health Network, Toronto

Brief Summary:
Chronically elevated free fatty acids impair insulin sensitivity and insulin secretion (ie lipotoxicity) by a combination of oxidative stress, endoplasmic reticulum (ER) stress and inflammation. This study will test whether alpha-lipoic acid, which has potent antioxidant and anti-inflammatory properties, prevents or ameliorates lipotoxicity.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Prediabetes Drug: alpha lipoic acid Phase 4

Detailed Description:

Alpha-Lipoic Acid (ALA) is a naturally occurring dithiol compound absorbed intact from dietary sources and synthesized enzymatically in the mitochondrion from octanoic acid. It serves a critical role in mitochondrial energy metabolism and is a potent biological antioxidant. It is widely available as an over-the-counter health supplement. It has generated considerable interest among the lay public and the research community for the use of ALA as a nutritive supplement and as a pharmacotherapy for diabetes and many other disorders. There is growing evidence that ALA has beneficial effects on the treatment of type 2 diabetes (T2DM) and some of its complications. It represents an attractive pharmacological target in the treatment of T2DM by modulating the signal transduction pathways in insulin resistance and antagonizing the oxidative and inflammatory stresses, which are major pathways in the pathogenesis of this disorder. Chronic elevation of plasma FFAs are believed to contribute to insulin resistance and defects in insulin secretion by promoting oxidative stress and inflammation. A potent antioxidant and free radical scavenger, ALA also targets cellular signal transduction pathways, which increases glucose uptake and utilization, thus providing specific targeted therapy in the treatment of insulin resistance. ALA has been shown to be safe when taken in high doses (2400mg/d) for prolonged time periods (6 months and longer), even in patients with renal and liver failure. In fact no upper limit for ALA consumption in humans has been established.

  • Each subject will undergo 4 studies, 4 to 6 weeks apart. Each study will consist of a 2 week treatment period with either oral ALA tablets or placebo tablets, followed by 30 hour hospital stay to infuse lipid or saline and to test insulin sensitivity and insulin secretion.
  • The study will be conducted as a single blind study, with the subject not knowing whether they are receiving a placebo or ALA. For safety reasons and since it will not influence the results of this study it will not be conducted as a double blind study.
  • On each of four occasions, 4 weeks apart, after taking the tablets for 2 weeks, the subject will fast overnight for 12-hours prior to their admission to the Toronto General Hospital metabolic research ward for 30 hours to undergo testing as follows. The four studies will be conducted in random order:

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: The Effect of A-lipoic Acid (ALA) on Fatty Acid-induced Impairment of Glucose-stimulated Insulin Secretion
Study Start Date : February 2010
Actual Primary Completion Date : January 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: alpha lipoic acid Drug: alpha lipoic acid
A 2 week treatment period with either oral ALA tablets or placebo tablets, followed by 30 hour hospital stay to infuse lipid or saline and to test insulin sensitivity and insulin secretion. For two weeks prior to each admission to hospital and during each hospital admission subjects will ingest 3 tablets 2 times per day with breakfast and supper, 1800mg per day
Other Names:
  • lipoic acid
  • ALA

Primary Outcome Measures :
  1. insulin secretion and insulin sensitivity To determine whether ALA ameliorates or prevents impairment of insulin secretion and insulin sensi [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. To determine the role of oxidative stress and inflammation in the pathogenesis of lipotoxicity [ Time Frame: 6 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Men and women aged 20-65 years:

  1. Written informed consent obtained
  2. Body mass index (BMI) > 27kg/m2
  3. Glucose tolerance test may be normal or demonstrate impaired glucose tolerance but not frank diabetes
  4. Hemoglobin above 130g/L

Exclusion Criteria:

  1. Subject has a history of hepatitis/hepatic disease that has been active within the previous two years
  2. Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 100 or systolic > 180) or proliferative retinopathy
  3. Type 2 diabetes by history or OGTT
  4. Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure
  5. Any laboratory values: AST > 2x ULN; ALT > 2x ULN; TSH > 6 mU/l
  6. A history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions. History of hypersensitivity to heparin
  7. Current addiction to alcohol or substances of abuse as determined by the investigator
  8. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
  9. Any lipid lowering of hypoglycemic agents
  10. Previous history of asthma
  11. Will not donate blood three months prior to and three months post study procedures
  12. Thrombocytopenia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01056497

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Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Canadian Diabetes Association
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Principal Investigator: gary F Lewis, MD University Health Network, Toronto General Hospital
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Responsible Party: Gary Lewis, Professor, Department of Medicine and Physiology, University Health Network, Toronto Identifier: NCT01056497    
Other Study ID Numbers: 090818B
Canadian Diabetes Association
First Posted: January 26, 2010    Key Record Dates
Last Update Posted: October 2, 2012
Last Verified: September 2012
Keywords provided by Gary Lewis, University Health Network, Toronto:
alpha lipoic acid
endoplasmic reticulum (ER) stress
insulin secretion
insulin sensitivity
Additional relevant MeSH terms:
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Prediabetic State
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Thioctic Acid
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances