We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01394510
First Posted: July 14, 2011
Last Update Posted: June 17, 2016
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.
Collaborator:
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Kristina Utzschneider, MD, Utzschneider, Kristina, M.D.
  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: Intervention Model: Single Group Assignment
Masking: None (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 Kristina Utzschneider, MD, Utzschneider, Kristina, M.D.:

Primary Outcome Measures:
  • Fasting Urine F2 Alpha Isoprostane Levels [ Time Frame: 4 weeks ]
    Change in fasting urine isoprostane levels at 4 weeks vs baseline as a marker of oxidative stress


Secondary Outcome Measures:
  • Area Under the Curve for Glucose (AUCg) [ Time Frame: 4 weeks ]
    Change in AUCg from 0-120 minutes during the oral glucose tolerance test at 4 weeks compared to baseline

  • Oral Disposition Index [ Time Frame: 4 weeks ]
    The change in the oral disposition index defined was the change in the early insulin response divided by the change in glucose from 0-30 minutes during the oral glucose tolerance test divided by fasting insulin.


Enrollment: 13
Study Start Date: June 2011
Study Completion Date: December 2015
Primary Completion Date: September 2014 (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

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.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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 human immunodeficiency virus (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 alanine aminotransferase (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
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 ClinicalTrials.gov identifier (NCT number): NCT01394510


Locations
United States, Washington
VA Puget Sound Health Care System
Seattle, Washington, United States, 98108
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

Publications:
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
First Submitted: July 12, 2011
First Posted: July 14, 2011
Results First Submitted: May 10, 2016
Results First Posted: June 17, 2016
Last Update Posted: June 17, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The study sample size is very small. The data will be made available upon request.

Keywords provided by Kristina Utzschneider, MD, 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
Expectorants
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes