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

NCT01394510 | Completed Results

• 1 other identifier: NACStudy001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; Oxidative Stress

Keywords

insulin secretion; beta-cell function; oxidative stress; type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• Fasting Urine F2 Alpha Isoprostane Levels

  Change in fasting urine isoprostane levels at 4 weeks vs baseline as a marker of oxidative stress

  4 weeks

Secondary Outcomes (2)

• Area Under the Curve for Glucose (AUCg)

  4 weeks

• Oral Disposition Index

  4 weeks

Study Arms (1)

N-acetylcysteine dose study

EXPERIMENTAL

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

Interventions

N-acetylcysteine DRUG

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.

Also known as: NAC

N-acetylcysteine dose study

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes

You may not qualify if:

• 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)

Sponsors & Collaborators

• Utzschneider, Kristina, M.D.: lead
• VA Puget Sound Health Care System: collaborator

Study Sites (1)

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Related Publications (1)

• 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.

  PMID: 26922582 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Kristina Utzschneider, MD
• Organization: VA Puget Sound Health Care System

kutzschn@uw.edu

206-277-3568

Study Officials

• Kristina Utzschneider, MD

  VA Puget Sound Health Care System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 14, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2015
• Last Updated: June 17, 2016
• Results First Posted: June 17, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)