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

Primary Purpose

Type 2 Diabetes, Oxidative Stress

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
N-acetylcysteine
Sponsored by
Utzschneider, Kristina, M.D.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 2 Diabetes focused on measuring insulin secretion, beta-cell function, oxidative stress, type 2 diabetes

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • VA Puget Sound Health Care System

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

N-acetylcysteine dose study

Arm Description

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.

Outcomes

Primary Outcome Measures

Fasting Urine F2 Alpha Isoprostane Levels
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)
Change in AUCg from 0-120 minutes during the oral glucose tolerance test at 4 weeks compared to baseline
Oral Disposition Index
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.

Full Information

First Posted
July 12, 2011
Last Updated
May 10, 2016
Sponsor
Utzschneider, Kristina, M.D.
Collaborators
VA Puget Sound Health Care System
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1. Study Identification

Unique Protocol Identification Number
NCT01394510
Brief Title
Effect of the Anti-oxidant N-acetylcysteine on Beta-cell Function in Type 2 Diabetes
Official Title
Effect of Anti-oxidants on Beta-cell Function in Humans
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Utzschneider, Kristina, M.D.
Collaborators
VA Puget Sound Health Care System

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Oxidative Stress
Keywords
insulin secretion, beta-cell function, oxidative stress, type 2 diabetes

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
N-acetylcysteine dose study
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
N-acetylcysteine
Other Intervention Name(s)
NAC
Intervention Description
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.
Primary Outcome Measure Information:
Title
Fasting Urine F2 Alpha Isoprostane Levels
Description
Change in fasting urine isoprostane levels at 4 weeks vs baseline as a marker of oxidative stress
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Area Under the Curve for Glucose (AUCg)
Description
Change in AUCg from 0-120 minutes during the oral glucose tolerance test at 4 weeks compared to baseline
Time Frame
4 weeks
Title
Oral Disposition Index
Description
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.
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristina Utzschneider, MD
Organizational Affiliation
VA Puget Sound Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Puget Sound Health Care System
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The study sample size is very small. The data will be made available upon request.
Citations:
PubMed Identifier
26922582
Citation
Szkudlinska MA, von Frankenberg AD, Utzschneider KM. The antioxidant N-Acetylcysteine does not improve glucose tolerance or beta-cell function in type 2 diabetes. J Diabetes Complications. 2016 May-Jun;30(4):618-22. doi: 10.1016/j.jdiacomp.2016.02.003. Epub 2016 Feb 5.
Results Reference
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Effect of the Anti-oxidant N-acetylcysteine on Beta-cell Function in Type 2 Diabetes

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