Clinical trial NCT01394510: 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
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Oxidative Stress
Keywords: insulin secretion
beta-cell function
oxidative stress
type 2 diabetes
Lead sponsor: Utzschneider, Kristina, M.D.
Sponsor class: INDIV
Collaborators: name: VA Puget Sound Health Care System
First posted: 2011-07-14
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Fasting Urine F2 Alpha Isoprostane Levels
timeFrame: 4 weeks
Secondary outcomes:
measure: Area Under the Curve for Glucose (AUCg)
timeFrame: 4 weeks
measure: Oral Disposition Index
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System
name: Kristina Utzschneider, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.