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

NCT01056497 | Completed Phase 4

• 2 other identifiers: 090818BCanadian Diabetes Association
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; Prediabetes

Keywords

diabetes; alpha lipoic acid; endoplasmic reticulum (ER) stress; insulin secretion; insulin sensitivity

Outcome Measures

Primary Outcomes (1)

• insulin secretion and insulin sensitivity To determine whether ALA ameliorates or prevents impairment of insulin secretion and insulin sensi

  6 months

Secondary Outcomes (1)

• To determine the role of oxidative stress and inflammation in the pathogenesis of lipotoxicity

  6 months

Study Arms (1)

alpha lipoic acid

EXPERIMENTAL

Drug: alpha lipoic acid

Interventions

alpha lipoic acid DRUG

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

Also known as: lipoic acid, ALA

alpha lipoic acid

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 20-65 years:
• Written informed consent obtained
• Body mass index (BMI) \> 27kg/m2
• Glucose tolerance test may be normal or demonstrate impaired glucose tolerance but not frank diabetes
• Hemoglobin above 130g/L

You may not qualify if:

• Subject has a history of hepatitis/hepatic disease that has been active within the previous two years
• 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
• Type 2 diabetes by history or OGTT
• 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
• Any laboratory values: AST \> 2x ULN; ALT \> 2x ULN; TSH \> 6 mU/l
• A history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions. History of hypersensitivity to heparin
• Current addiction to alcohol or substances of abuse as determined by the investigator
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
• Any lipid lowering of hypoglycemic agents
• Previous history of asthma
• Will not donate blood three months prior to and three months post study procedures
• Thrombocytopenia

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Canadian Diabetes Association: collaborator

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Prediabetic State; Diabetes Mellitus; Insulin Resistance

Interventions

Thioctic Acid

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids

Study Officials

• gary F Lewis, MD

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Medicine and Physiology

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: January 26, 2010
• Study Start: February 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: June 1, 2011
• Last Updated: October 2, 2012

Record last verified: 2012-09

Locations

CA (1)