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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

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

NCT ID

NCT01394510

First Posted

July 12, 2011

Last Updated

May 10, 2016

Sponsor

Utzschneider, Kristina, M.D.

Collaborators

VA Puget Sound Health Care System

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

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

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

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

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

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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