Antioxidant Use in Diabetes to Reduce Oxidative Stress

• ClinicalTrials.gov Identifier: NCT03056014
• Recruitment Status: Active, not recruiting
• First Posted: February 16, 2017
• Last Update Posted: October 19, 2020
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Sarah Crimmins, University of Maryland, College Park

Study Description

Brief Summary:

Dietary supplementation with antioxidant vitamins, such as Vitamin C and Vitamin E, reduces malformation rates in embryos of diabetic animals. However, human trials exploring the benefits of these antioxidant vitamins have produced unsatisfactory results in trials designed to alleviating diabetic retinopathy, cardiovascular disease, and preeclampsia in pregnancies. The investigators hypothesize that more potent, and better-targeted antioxidants, such as N-acetylcysteine (NAC) and Polyunsaturated Fatty Acids(PUFA), will be successful in preventing birth defects in the offspring of women with diabetes.

Condition or disease	Intervention/treatment	Phase
Ameliorating Oxidative Stress in Type 1 Diabetes	Drug: N-acetyl cysteine; Dietary Supplement: omega 6 Fish oil ( PUFA); Dietary Supplement: Placebo	Early Phase 1

Detailed Description:

Specific Aim 1. Recruit non pregnant women with T1DM and investigate the efficacy of dietary NAC on ameliorating oxidative stress Study design. Diabetic patients will be provided with NAC or placebo for 14 days, while receiving usual clinical care. The oxidative stress status will be assessed by measuring biomarkers in blood samples pre and post intervention. In addition to a placebo control group, three treatment groups including Group 1 (NAC 600 mg/day), Group 2 (NAC 1200 mg/day), and Group 3 (NAC 1800 mg/day) will be studied. The choice of dosage of NAC is based on published studies, which show effectiveness of NAC in 600 or 1200 mg day in alleviating oxidative stress in diabetic patients, both in men and women, without adverse side effects. The investigators will use the supplement company TwinLab for our study. The university of Maryland Pharmacy department will analyze the NAC for purity prior to starting the study. At day 7, participants will be called via phone assess for symptoms and side effects from medications. All participants will be called. At the end of 14 days, the patients will return to the CDE with a survey asking about compliance with medication and any side effects. They will also bring the pill bottle so that study personnel can do a pill count. At this time blood will be draw for the biomarker levels to look for changes in oxidative stress.

Specific Aim 2. To investigate effect of PUFAs on ameliorating oxidative stress in diabetic non-pregnant women.

Study design: The investigators will recruit a new group of Non-pregnant women with T1DM will be enrolled and randomly assigned to placebo or one of three treatment groups. Study volunteers will be divided into 1 of 3 groups. PUFA; Group 1 (1000 mg/day) or Group 2 (2000 mg/day) or Group 3(placebo). The treatment regimens, sample collection, biomarker assessment, side effect monitoring and statistical analysis will be performed as described in SA 1. The investigators will perform an analysis of the oxidative stress biomarkers as described in SA1. The investigators will use TwinLab as our commercial supplier of PUFA for our trial. There fish oil supplements have been involved in greater than 40 published trials. The fish oil supplement will be analyzed by the University of Maryland pharmacy department prior to starting the study to analyze for purity.

Specific Aim 3: To investigate the potential secondary benefit of NAC/PUFA on kidney function and lipid profile. Urine and serum samples will be collected on all enrolled subjects at day 0 and Day 14 to monitor for improvement in microalbumin in the urine and lipid profile in the serum. Previous studies have shown improvements in LDL with supplementation of NAC. The investigators will look at how various dosages effect the improvement in microalbumin and lipid profile.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Masking Description: Double blind
• Primary Purpose: Treatment
• Official Title: Supplementation of N-acetylcysteine and Arachonic Acid in Type 1 Diabetes to Determine Changes in Oxidative Stress
• Actual Study Start Date: November 1, 2018
• Estimated Primary Completion Date: December 1, 2022
• Estimated Study Completion Date: June 2, 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: N-acetylcysteine 600 mg	Drug: N-acetyl cysteine; giving varying doses of NAC in order to determine which reduces oxidative stress.
Active Comparator: N-acetylcysteine 1200 mg	Drug: N-acetyl cysteine; giving varying doses of NAC in order to determine which reduces oxidative stress.
Placebo Comparator: placebo	Dietary Supplement: Placebo; L-alanine placebo pill to determine if effect is supplement related or random effect.
Active Comparator: PUFA 1000 mg	Dietary Supplement: omega 6 Fish oil ( PUFA); giving varying doses of PUFA in order to determine which reduces oxidative stress.
Active Comparator: PUFA 2000 mg	Dietary Supplement: omega 6 Fish oil ( PUFA); giving varying doses of PUFA in order to determine which reduces oxidative stress.
Placebo Comparator: Placebo	Dietary Supplement: Placebo; L-alanine placebo pill to determine if effect is supplement related or random effect.

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in level of oxidative stress with varying doses of NAC at 2 weeks. [ Time Frame: 2 weeks ]
2. Change from baseline in level of oxidative stress with varying doses of omega 6 fish oil(PUFA) at 2 weeks. [ Time Frame: 2 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 44 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: we specifically want to study this in reproductive age females.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• hemoglobin a1c <10
• type 1 diabetes

Exclusion Criteria:

• pregnancy
• BMI > 40
• greater than 1 alcoholic beverages per week
• any tobacco use
• prescribed nitroglycerin, HIV protease inhibits, corticosteroids, cephalosporins, or blood thinners
• vascular complications(history of coronary artery disease, cerebral vascular accident, transient ischemic attack, claudication).

Contacts and Locations

Locations

United States, Maryland

University of Maryland, Baltimore

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland, Baltimore

More Information

• Responsible Party: Sarah Crimmins, Assistant Professor, University of Maryland, College Park
• ClinicalTrials.gov Identifier: NCT03056014
• Other Study ID Numbers: HP-00067782
• First Posted: February 16, 2017
• Last Update Posted: October 19, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Acetylcysteine; N-monoacetylcystine; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes