N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy

NCT00915200 | Completed Phase 2 DMC

• 3 other identifiers: NIH 1R21AT0044901I01CX000264-01A2R21AT004490
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to test if the combination of two potent antioxidant nutritional supplements, N-acetylcysteine and the milk thistle extract silibin, is capable of correcting the shedding of urine protein, the oxidative stress, and the inflammation in patients with type 2 diabetes mellitus and diabetic kidney disease.

Conditions

Diabetic Nephropathies; Proteinuria; Oxidative Stress

Keywords

Diabetic Nephropathies; Proteinuria; Renal Insufficiency, Chronic; Monocytes; Oxidative stress; Inflammation; Antioxidants; Glutathione; Silymarin; Acetylcysteine; Dietary Supplements; Complementary Therapies

Outcome Measures

Primary Outcomes (1)

• Urinary Albumin excretion

  3-month

Secondary Outcomes (4)

• urinary alpha-1 microglobulin excretion

  3-month

• urinary C-C-chemokines excretion

  3-month

• peripheral blood monocyte glutathione content

  3-month

• tolerance and safety

  3-month

Study Arms (5)

Placebo

PLACEBO COMPARATOR

N-acetylcysteine placebo + silibin placebo

Dietary Supplement: N-acetylcysteine placebo; Dietary Supplement: silibin placebo

N-acetylcysteine

EXPERIMENTAL

N-acetylcysteine active + silibin placebo

Dietary Supplement: N-acetylcysteine; Dietary Supplement: silibin placebo

silibin

EXPERIMENTAL

N-acetylcysteine placebo + silibin active

Dietary Supplement: silibin; Dietary Supplement: N-acetylcysteine placebo; Dietary Supplement: silibin placebo

N-acetycysteine + silibin

EXPERIMENTAL

N-acetylcysteine active + silibin active

Dietary Supplement: N-acetylcysteine; Dietary Supplement: silibin; Dietary Supplement: silibin placebo

N-acetylcysteine + high-dose silibin

EXPERIMENTAL

N-acetylcysteine active + high-dose silibin active

Dietary Supplement: N-acetylcysteine; Dietary Supplement: high-dose silibin

Interventions

N-acetylcysteine DIETARY_SUPPLEMENT

600 mg orally twice daily for three months

Also known as: NAC

N-acetycysteine + silibin; N-acetylcysteine; N-acetylcysteine + high-dose silibin

silibin DIETARY_SUPPLEMENT

480 mg orally twice daily for three months

Also known as: silibin-phosphatidylcholine, Siliphos

N-acetycysteine + silibin; silibin

high-dose silibin DIETARY_SUPPLEMENT

960 mg orally twice daily for three months

Also known as: silibin-phosphatidylcholine, Siliphos

N-acetylcysteine + high-dose silibin

N-acetylcysteine placebo DIETARY_SUPPLEMENT

excipient orally twice daily for three months

Also known as: NAC placebo

Placebo; silibin

silibin placebo DIETARY_SUPPLEMENT

excipient orally twice daily for three months

Also known as: silibin-phosphatidylcholine placebo, Siliphos placebo

N-acetycysteine + silibin; N-acetylcysteine; Placebo; silibin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females, age 18-70 years old.
• Type 2 diabetes mellitus
• Diabetic nephropathy, as defined by:
• estimated GFR between 60 and 15 ml/min,
• presence of proteinuria.
• Current medical treatment with low dose aspirin
• Treatment of hypertension with (but not limited to) one diuretic, one beta- blocker and one medication from the classes ARBs or ACE inhibitors.
• Treatment of hyperglycemia with (but not limited to) glipizide and the medication class insulin.
• Treatment of hypercholesterolemia with (but not limited to) one medication from the class statins.

You may not qualify if:

• Type 1 diabetes mellitus.
• Glycosylated hemoglobin (HbA1C) \> 10%
• \>20% variation in estimated GFR, during last 6 months
• SBP \>170 mmHg or DBP \>100 mmHg on medications
• Other secondary forms of hypertension (endocrine, renovascular)
• History of intolerance to:
• Both ACE-I and ARBs;
• The investigational supplements;
• Iodinated radiologic contrast material.
• Known non diabetic renal disease, or history of solid organ transplantation.
• Hepatitis virus or Human Immunodeficiency virus infections
• Use of one of the following medications within 2 months prior to enrollment in the study:
• Metformin.
• Thiazolidinediones (pioglitazone or rosiglitazone);
• Prescription-grade vitamin E, vitamin C, systemic steroids, and/or non-steroidal anti-inflammatory agents;

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• VA Office of Research and Development: collaborator

Study Sites (1)

University of Texas Hlth Sci Ctr San Ant

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev. 2023 Nov 2;11(11):CD008176. doi: 10.1002/14651858.CD008176.pub3.

  PMID: 37916745 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Proteinuria; Renal Insufficiency, Chronic; Inflammation

Interventions

Acetylcysteine; Silybin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Silymarin; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Paolo Fanti, M.D.

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2009
• First Posted: June 5, 2009
• Study Start: October 1, 2009
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: June 27, 2016

Record last verified: 2016-06

Locations

US (1)