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Trial · Interventional

CompletedPhase 2Results postedRegistry data

N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy

Short name CGDN

NCTNCT01265563 (opens ClinicalTrials.gov in a new tab)Other idCLIN-004-10SOther id1R21AT004490-01A1Other idVA 1I01CX000264-01A2
Open at ClinicalTrials.govAsk about this trial

This trial does not test a peptide that PepBank tracks.

  • Measures Glutathione, does not give it. It appears in the eligibility rules.

Overview

Status
Completed
Phase
Phase 2
Enrollment
108 participants (actual)
Sponsor
VA Office of Research and Development · Fed
Design
Randomized · Triple masking
Countries
1 country

United States

Start
Jan 2011
Primary completion
Feb 2015
Completion
Dec 2016
First posted
23 Dec 2010 (estimated)
Last update posted
19 Oct 2018
Conditions
Diabetic Nephropathy · Proteinuria · Oxidative Stress

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2011201220132014201520162017
  1. Ph 2

    CGDN

    NCT01265563

    Jan 2011 to Dec 2016

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The study is done to find out whether the combined use of the nutritional supplements N-acetylcysteine and Siliphos (milk thistle extract) corrects the shedding of urine protein and oxidative damage (damage to cells and organs often compared to fast aging) in patients with Type 2 Diabetes Mellitus (T2DM) and diabetic kidney disease.

Interventions

  • N-acetylcysteine placebo and silibin placeboDrug
  • N-acetylcysteine active and silibin placeboDrug
  • N-acetylcysteine placebo and silibin activeDrug
  • N-acetylcysteine active and silibin activeDrug
  • N-acetylcysteine active + high-dose silibin activeDrug

Arms5

  • Placebo comparator

    NAC placebo and Silibin placebo

    Drug: N-acetylcysteine placebo and Drug: Silibin placebo

  • Experimental

    NAC active and Silibin placebo

    Drug: N-acetylcysteine and Drug: Silibin placebo

  • Experimental

    NAC placebo and Silibin active

    Drug: N-acetylcysteine placebo and Drug: Silibin active

  • Experimental

    NAC active and Silibin active

    Drug: N-acetylcysteine active and Drug: Silibin active

  • Experimental

    NAC active and High-dose Silibin active

    Drug: N-acetylcysteine active and Drug: Silibin higher dose active

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change From Baseline in Urinary Albumin Excretion

    Time frame · Baseline and 3 months

    Registry description

    Urine albumin to creatinine ratio was assessed at the end of run in period and after 3 months administration of study intervention.

Secondary outcomes(2)

  1. Change From Baseline in Hemoglobin-A1c

    Time frame · Baseline and 3 months

    Registry description

    Hemoglobin A1C was assessed at the end of the run in period and after 3 months of administration of study interventions. Here is delta HgA1C is reported between the two periods

  2. Urinary Alpha-1 Microglobulin, Inflammatory Cytokines and C-C Chemokines

    Time frame · Baseline and 3 months

    Registry description

    Urinary alpha-1 microglobulin, inflammatory cytokines and C-C chemokines were never measured and analyzed.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline and 3 months

Change From Baseline in Urinary Albumin Excretion

GroupValue (mg/g)Spread
NAC Placebo + Silibin Placebo50.5291.2
NAC Active + Silibin Placebo-28.13578.32
NAC Placebo + Silibin Active-4.5541
NAC Active + Silibin Active96.6422.4
NAC Active + High-dose Silibin Active353.71732.67
Secondary and other outcome results(2)
Secondary outcomeMean· Baseline and 3 months

Change From Baseline in Hemoglobin-A1c

GroupValue (percentage)Spread
NAC Placebo + Silibin Placebo0.350.58
NAC Active + Silibin Placebo-0.180.68
NAC Placebo + Silibin Active0.722.91
NAC Active + Silibin Active0.42.19
NAC Active + High-dose Silibin Active0.21.14
Secondary outcome· Baseline and 3 months

Urinary Alpha-1 Microglobulin, Inflammatory Cytokines and C-C Chemokines

GroupValue
NAC Placebo and Silibin Placebonot posted
NAC Active and Silibin Placebonot posted
NAC Placebo and Silibin Activenot posted
NAC Active and Silibin Activenot posted
NAC Active and High-dose Silibin Activenot posted

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
NAC Placebo + Silibin PlaceboN-acetylcysteine placebo + silibin placebo Dietary Supplement: N-acetylcysteine placebo excipient orally twice daily for three months Other Name: NAC placebo Dietary Supplement: silibin placebo excipient orally twice daily for three months Other Name: silibin-phosphatidylcholine placebo, Siliphos placebo N-acetylcysteine placebo + silibin placebo: Dietary Supplement: N-acetylcysteine placebo excipient orally twice daily for three months0 / 161 / 167 / 16
NAC Active + Silibin PlaceboN-acetylcysteine active + silibin placebo Dietary Supplement: N-acetylcysteine 600 mg orally twice daily for three months Other Name: NAC Dietary Supplement: silibin placebo excipient orally twice daily for three months Other Name: silibin-phosphatidylcholine placebo, Siliphos placebo N-acetylcysteine active + silibin placebo: Dietary Supplement: N-acetylcysteine 600 mg orally twice daily for three months0 / 121 / 127 / 12
NAC Placebo + Silibin ActiveN-acetylcysteine placebo + silibin active Dietary Supplement: silibin 480 mg orally twice daily for three months Other Name: silibin-phosphatidylcholine, Siliphos Dietary Supplement: N-acetylcysteine placebo excipient orally twice daily for three months Other Name: NAC placebo Dietary Supplement: silibin placebo excipient orally twice daily for three months Other Name: silibin-phosphatidylcholine placebo, Siliphos placebo N-acetylcysteine placebo + silibin active: Dietary Supplement: silibin 480 mg orally twice daily for three months * (Other Name) Silibin-phosphatidylcholine placebo, Siliphos placebo * (Other Name) NAC placebo Dietary Supplement: silibin placebo excipient orally twice daily for three months0 / 161 / 166 / 16
NAC Active + Silibin ActiveN-acetylcysteine active + silibin active Dietary Supplement: N-acetylcysteine 600 mg orally twice daily for three months Other Name: NAC Dietary Supplement: silibin 480 mg orally twice daily for three months Other Name: silibin-phosphatidylcholine, Siliphos Dietary Supplement: silibin placebo excipient orally twice daily for three months Other Name: silibin-phosphatidylcholine placebo, Siliphos placebo N-acetylcysteine active + silibin active: Dietary Supplement: N-acetylcysteine 600 mg orally twice daily for three months * (Other Name): NAC Dietary Supplement: silibin 480 mg orally twice daily for three months Silibin-phosphatidylcholine, Siliphos Dietary Supplement: silibin placebo excipient orally twice daily for three months * (Other Name): Silibin-phosphatidylcholine, Siliphos Dietary Supplement: silibin placebo excipient orally twice daily for three months0 / 161 / 168 / 16
NAC Active + High-dose Silibin ActiveN-acetylcysteine active + high-dose silibin active Dietary Supplement: N-acetylcysteine 600 mg orally twice daily for three months Other Name: NAC Dietary Supplement: high-dose silibin 960 mg orally twice daily for three months Other Name: silibin-phosphatidylcholine, Siliphos N-acetylcysteine active + high-dose silibin active: Dietary Supplement: N-acetylcysteine 600 mg orally twice daily for three months0 / 141 / 149 / 14

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultKhazim K, Giustarini D, Rossi R, Verkaik D, Cornell JE, Cunningham SE, Mohammad M, Trochta K, Lorenzo C, Folli F, Bansal S, Fanti P. Glutathione redox potential is low and glutathionylated and cysteinylated hemoglobin levels are elevated in maintenance hemodialysis patients. Transl Res. 2013 Jul;162(1):16-25. doi: 10.1016/j.trsl.2012.12.014. Epub 2013 Jan 17. PMID 23333585
  • ResultCunningham SE, Verkaik D, Gross G, Khazim K, Hirachan P, Agarwal G, Lorenzo C, Matteucci E, Bansal S, Fanti P. Comparison of Nutrition Profile and Diet Record Between Veteran and Nonveteran End-Stage Renal Disease Patients Receiving Hemodialysis in Veterans Affairs and Community Clinics in Metropolitan South-Central Texas. Nutr Clin Pract. 2015 Oct;30(5):698-708. doi: 10.1177/0884533615575046. Epub 2015 Apr 21. PMID 25899538
  • ResultFanti P, Giustarini D, Rossi R, Cunningham SE, Folli F, Khazim K, Cornell J, Matteucci E, Bansal S. Dietary Intake of Proteins and Calories Is Inversely Associated With The Oxidation State of Plasma Thiols in End-Stage Renal Disease Patients. J Ren Nutr. 2015 Nov;25(6):494-503. doi: 10.1053/j.jrn.2015.06.003. Epub 2015 Jul 31. PMID 26235932
  • ResultGiustarini D, Galvagni F, Orlandini M, Fanti P, Rossi R. Immediate stabilization of human blood for delayed quantification of endogenous thiols and disulfides. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 15;1019:51-8. doi: 10.1016/j.jchromb.2016.02.009. Epub 2016 Feb 8. PMID 26896310
  • ResultKhazim K, Gorin Y, Cavaglieri RC, Abboud HE, Fanti P. The antioxidant silybin prevents high glucose-induced oxidative stress and podocyte injury in vitro and in vivo. Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F691-700. doi: 10.1152/ajprenal.00028.2013. Epub 2013 Jun 26. PMID 23804455

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 76 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Males or females age 18-76 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 Angiotensin Receptor Blockers (ARBs) or Angiotensin Converting Enzyme inhibitors (ACE-I) * 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 Exclusion Criteria: * Type 1 diabetes mellitus * Glycosylated hemoglobin (HbA1C) \> 10% * \>20% variation in estimated GFR, during last 6 months * Systolic Blood Pressure \>170 mmHg or Diastolic Blood Pressure \>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) * Phenytoin * Warfarin * Prescription-grade vitamin E, vitamin C, systemic steroids, and/or non-steroidal anti-inflammatory agents * Over-the-counter vitamin E, vitamin C, and/or non-steroidal anti-inflammatory agents * Over-the-counter antioxidants supplements including: * Lipoic acid * Coenzyme Q10 * N-acetyl-cysteine (NAC) * Glutathione (GSH) * Chromium * Fish-oil extracts (omega-3 fatty acids) * Soy extracts (isoflavones) * Milk thistle extract (silymarin) * Green-tea preparations * Pomegranate extracts * Grape extracts * Prickly pear extract * Active coronary artery disease or cerebral vascular disease within 3 months prior to signing the informed consent * Hepatic dysfunction as defined by abnormal total bilirubin or liver enzymes (ALT, AST) \>2 times upper limit of normal range * Active malignancy * History of drug or alcohol dependency * Psychiatric or neurological condition, preventing aware consent to the study and/or adherence to the study protocol * Unwillingness to practice birth control throughout the study * Participation to another clinical study within 1 month prior to signing the informed consent form * Planned move to outside the study area, surgery or radiographic studies utilizing iodine-based contrast material within the next one year

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