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

Type 2 Diabetes Clinical Trial

Official title:

Effect of Anti-oxidants on Beta-cell Function in Humans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01394510
• Other study ID #: NACStudy001
• Status: Recruiting
• Phase: N/A
• First received: July 12, 2011
• Last updated: August 15, 2014
• Start date: June 2011
• Est. completion date: October 2016

Study information

• Verified date: August 2014
• Source: Utzschneider, Kristina, M.D.
• Contact: Tonya Johnson
• Phone: 206-277-5072
• Email: tonya.johnson2[@]va.gov
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 2016
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Oxidative Stress
• Type 2 Diabetes

Intervention

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.

Locations

Country	Name	City	State
United States	VA Puget Sound Health Care System	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Utzschneider, Kristina, M.D.	VA Puget Sound Health Care System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fasting urine F2 alpha isoprostane levels	Fasting urine isoprostane levels as a marker of oxidative stress	4 weeks	No
Secondary	side-effect profile	Side effect profile as determined by a standardized questionnaire	4 weeks	Yes
Secondary	Area under the curve for glucose (AUCg)	AUCg from 0-120 minutes during the oral glucose tolerance test	4 weeks	No
Secondary	oral disposition index	The oral disposition index will be measured by mathematical modeling of oral glucose tolerance test data to assess beta-cell function.	4 weeks	No