Effect of the Anti-oxidant N-acetylcysteine on Beta-cell Function in Type 2 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Utzschneider, Kristina, M.D.
Sponsor:
Collaborator:
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Kristina Utzschneider, MD, Utzschneider, Kristina, M.D.
ClinicalTrials.gov Identifier:
NCT01394510
First received: July 12, 2011
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

Insulin is secreted by cells in the pancreas called beta-cells. Beta-cell dysfunction is a critical feature of type 2 diabetes (T2DM). High glucose levels can exacerbate beta-cell dysfunction with oxidative stress proposed as a major mediator of this "glucotoxic" effect. High glucose levels have also been shown to contribute to vascular dysfunction and inflammation and these adverse responses decreased with the use of antioxidants. The hypothesis is that antioxidants improve beta-cell function in individuals with elevated glucose levels by decreasing oxidative stress. In this study the investigators will specifically test whether the antioxidant N-acetylcysteine (NAC) can improve beta-cell function in individuals with type 2 diabetes by decreasing oxidative stress.

This study will be a dose finding study to determine the tolerability of 600 mg versus 1200 mg twice a day of NAC and the effects on beta-cell function, glucose tolerance and oxidative stress markers in persons with type 2 diabetes.


Condition Intervention
Type 2 Diabetes
Oxidative Stress
Drug: N-acetylcysteine

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Anti-oxidants on Beta-cell Function in Humans

Resource links provided by NLM:


Further study details as provided by Utzschneider, Kristina, M.D.:

Primary Outcome Measures:
  • fasting urine F2 alpha isoprostane levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Fasting urine isoprostane levels as a marker of oxidative stress


Secondary Outcome Measures:
  • side-effect profile [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Side effect profile as determined by a standardized questionnaire

  • Area under the curve for glucose (AUCg) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    AUCg from 0-120 minutes during the oral glucose tolerance test

  • oral disposition index [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    The oral disposition index will be measured by mathematical modeling of oral glucose tolerance test data to assess beta-cell function.


Estimated Enrollment: 20
Study Start Date: June 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: N-acetylcysteine dose study
Subjects will take N-acetylcysteine (NAC) 600 mg twice daily for 2 weeks, then 1200 mg twice daily for an additional 2 weeks. Study procedures will be performed at baseline, after 2 weeks and after 4 weeks.
Drug: N-acetylcysteine
600 mg N-acetylcysteine (NAC) twice daily by mouth for 2 weeks followed by 1200 mg NAC twice daily by mouth for 2 additional weeks.
Other Name: NAC

Detailed Description:

Beta-cell dysfunction is a critical feature of type 2 diabetes (T2DM). High glucose levels can exacerbate beta-cell dysfunction with oxidative stress proposed as a major mediator of this "glucotoxic" effect. High glucose levels have also been shown to contribute to vascular dysfunction and inflammation and these adverse responses decreased with the use of antioxidants. The hypothesis is that antioxidants improve beta-cell function in individuals with elevated glucose levels by decreasing oxidative stress. In this study the investigators will specifically test whether the antioxidant N-acetylcysteine (NAC) can improve beta-cell function in individuals with type 2 diabetes by decreasing oxidative stress.

This initial study will be a dose finding study to determine the tolerability of 600 mg versus 1200 mg twice a day of NAC and the effects of NAC treatment on beta-cell function, glucose tolerance and oxidative stress markers in persons with type 2 diabetes. Study procedures will include a fasting urine sample and performance of a 2 hour 75 gram oral glucose tolerance test at baseline, after 2 weeks on 600 mg twice daily NAC and again after 2 more weeks on 1200 mg NAC twice a day.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes

Exclusion Criteria:

  • Pregnant or lactating females
  • Uncontrolled diabetes mellitus with severe hyperglycemia (hemoglobin A1C ≥ 9%)
  • Patients with diabetes mellitus who are taking insulin or glucose-lowering agents other than metformin
  • Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 8 weeks prior to screening
  • Use of HIV protease inhibitors or niacin
  • Chronic inflammatory diseases or use of anti-inflammatory drugs.
  • Thyroid abnormalities (thyroid-stimulating hormone [TSH] <0.5 or >5 µU/ml)
  • Creatinine >1.5 in men and >1.3 mg/dl in women
  • History of dysphagia, gastroparesis, gastric ulcer, malabsorption, swallowing disorders or intestinal motility disorder
  • Gastroesophageal reflux disease (heartburn) requiring treatment.
  • Active cancer
  • Clinical hepatic disease or ALT greater than ≥ 1.5 times upper limit of normal within 60 days preceding the first dose of the study drug
  • Weight loss of >5% body weight within the last 6 months, or starting an intensive exercise program within 4 weeks of study initiation
  • Smoke or use tobacco
  • Excessive alcohol consumption (>2 drinks a day)
  • Use of any investigational drug in the last 30 days
  • Anemia (hematocrit <33%), donation of one unit (500 ml) or more of blood, significant blood loss equaling at least one unit of blood within the past 2 weeks or a blood transfusion within 8 weeks prior to screening
  • Employment by the research center
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01394510

Contacts
Contact: Tonya Johnson 206-277-5072 tonya.johnson2@va.gov
Contact: Kristina Utzschneider, MD 206-277-3568 kutzschn@u.washington.edu

Locations
United States, Washington
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98108
Contact: Tonya Johnson    206-277-5072    tonya.johnson2@va.gov   
Principal Investigator: Kristina Utzschneider, MD         
Sponsors and Collaborators
Utzschneider, Kristina, M.D.
VA Puget Sound Health Care System
Investigators
Principal Investigator: Kristina Utzschneider, MD VA Puget Sound Health Care System
  More Information

No publications provided

Responsible Party: Kristina Utzschneider, MD, Associate Professor of Medicine, Utzschneider, Kristina, M.D.
ClinicalTrials.gov Identifier: NCT01394510     History of Changes
Other Study ID Numbers: NACStudy001
Study First Received: July 12, 2011
Last Updated: August 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Utzschneider, Kristina, M.D.:
insulin secretion
beta-cell function
oxidative stress
type 2 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Acetylcysteine
N-monoacetylcystine
Antioxidants
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on September 18, 2014