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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21AT004490-01A1 | U.S. NIH Grant/Contract | View source | |
| VA 1I01CX000264-01A2 | Registry Identifier | VA |
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| Name | Class |
|---|---|
| National Center for Complementary and Integrative Health (NCCIH) | NIH |
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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.
Oxidative stress and glutathione (GSH) imbalance are major contributors to the pathogenesis of diabetic nephropathy. Current options for the treatment of oxidative stress in diabetic nephropathy are limited and only partially effective, thus interest in the development of new strategies is high.
The study intends to test the hypothesis that combined oral supplementation of the antioxidants N-acetylcysteine (NAC) and milk thistle flavonolignan silibin (as silibin-phosphatidylcholine) will reduce proteinuria and urinary and systemic manifestations of oxidative stress and inflammation, which are characteristically observed in patients with T2DM and related nephropathy. The investigators expect these effects to be achieved with minimal or no side effects, and with good patient tolerance.
The trial is designed as a two-center, double-blind, placebo-controlled, randomized, modified-factorial dose-ranging design, five-arm pilot study in patients with Type 2 diabetes mellitus and advanced diabetic nephropathy with proteinuria.
Intervention consists of three-month oral administration of NAC, silibin, and/or respective placebos for three months. Subjects are randomized to the following five intervention arms: (A) placebo; (B) NAC; (C) silibin; (D) NAC + silibin; and (E) NAC + double-dose silibin.
The primary outcome measure is urinary excretion of albumin, a marker of glomerular injury. Secondary outcome measures are alpha-1 microglobulin, a marker of tubular injury, and urinary excretion of inflammatory cytokines and C-C chemokines, i.e. markers of renal inflammation. In addition, peripheral blood monocytes from the same patients are analyzed for GSH content and activity of GSH metabolizing enzymes. All outcome measures are monitored in relation to both treatment allocation and prevalent blood and urine levels of the active treatment. Safety and tolerability of this combination treatment are monitored throughout the trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NAC placebo and Silibin placebo | Placebo Comparator | Drug: N-acetylcysteine placebo and Drug: Silibin placebo |
|
| NAC active and Silibin placebo | Experimental | Drug: N-acetylcysteine and Drug: Silibin placebo |
|
| NAC placebo and Silibin active | Experimental | Drug: N-acetylcysteine placebo and Drug: Silibin active |
|
| NAC active and Silibin active | Experimental | Drug: N-acetylcysteine active and Drug: Silibin active |
|
| NAC active and High-dose Silibin active | Experimental | Drug: N-acetylcysteine active and Drug: Silibin higher dose active |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-acetylcysteine placebo and silibin placebo | Drug | Dietary Supplement: N-acetylcysteine placebo excipient and silibin placebo orally twice daily for three months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Urinary Albumin Excretion | Urine albumin to creatinine ratio was assessed at the end of run in period and after 3 months administration of study intervention. | Baseline and 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Hemoglobin-A1c | 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 | Baseline and 3 months |
| Urinary Alpha-1 Microglobulin, Inflammatory Cytokines and C-C Chemokines |
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Inclusion Criteria:
Males or females age 18-76 years old
Type 2 diabetes mellitus
Diabetic nephropathy, as defined by:
Current medical treatment with low dose aspirin
Treatment of hypertension with (but not limited to):
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:
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:
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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| Name | Affiliation | Role |
|---|---|---|
| Paolo Fanti, MD | South Texas Health Care System, San Antonio, TX | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| South Texas Health Care System, San Antonio, TX | San Antonio | Texas | 78229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22445478 | Background | Debnath S, Thameem F, Alves T, Nolen J, Al-Shahrouri H, Bansal S, Abboud HE, Fanti P. Diabetic nephropathy among Mexican Americans. Clin Nephrol. 2012 Apr;77(4):332-44. doi: 10.5414/cn107487. | |
| 23928499 | Background | Giustarini D, Dalle-Donne I, Milzani A, Fanti P, Rossi R. Analysis of GSH and GSSG after derivatization with N-ethylmaleimide. Nat Protoc. 2013 Sep;8(9):1660-9. doi: 10.1038/nprot.2013.095. Epub 2013 Aug 1. |
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During Run-in phase before randomization to the experimental arms, 4 subjects were excluded due to hospitalization for various reasons and 26 were excluded due to issues with transportation or sickness in the family or themselves.
213 subjects met the inclusion criteria on screening from 2 clinic locations: VA and University Hospital Renal clinics.Many had exclusion criteria and few refused to participate. 108 subjects finally enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | NAC Placebo + Silibin Placebo | N-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 months |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| N-acetylcysteine active and silibin placebo | Drug | Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin placebo orally twice a day for three months |
|
|
| N-acetylcysteine placebo and silibin active | Drug | Dietary Supplement: silibin 480 mg orally twice daily and N-acetylcysteine placebo orally twice a day for three months |
|
|
| N-acetylcysteine active and silibin active | Drug | Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 480 mg orally twice daily for three months |
|
|
| N-acetylcysteine active + high-dose silibin active | Drug | Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 960 mg orally twice daily for three months |
|
|
Urinary alpha-1 microglobulin, inflammatory cytokines and C-C chemokines were never measured and analyzed. |
| Baseline and 3 months |
| 23333585 | Result | Khazim 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. |
| 25899538 | Result | Cunningham 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. |
| 26235932 | Result | Fanti 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. |
| 26896310 | Result | Giustarini 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. |
| 23804455 | Result | Khazim 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. |
| FG001 | NAC Active + Silibin Placebo | N-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 months |
| FG002 | NAC Placebo + Silibin Active | N-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
|
| FG003 | NAC Active + Silibin Active | 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 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
|
| FG004 | NAC Active + High Dose Silibin Active | N-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 months |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NAC Placebo and Silibin Placebo | N-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 months |
| BG001 | NAC Active and Silibin Placebo | N-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 months |
| BG002 | NAC Placebo and Silibin Active | N-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
|
| BG003 | NAC Active and Silibin Active | 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 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
|
| BG004 | NAC Active and High-dose Silibin Active | N-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 months |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| BMI | Mean | Standard Deviation | kg/M^2 |
| |||||||||||||||
| Systolic BP | Mean | Standard Deviation | mmHg |
| |||||||||||||||
| Diastolic BP | Mean | Standard Deviation | mmHg |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Urinary Albumin Excretion | Urine albumin to creatinine ratio was assessed at the end of run in period and after 3 months administration of study intervention. | Posted | Mean | Standard Deviation | mg/g | Baseline and 3 months |
|
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Hemoglobin-A1c | 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 | Posted | Mean | Standard Deviation | percentage | Baseline and 3 months |
| ||||||||||||||||||||||||||||||||||||||||
| Secondary | Urinary Alpha-1 Microglobulin, Inflammatory Cytokines and C-C Chemokines | Urinary alpha-1 microglobulin, inflammatory cytokines and C-C chemokines were never measured and analyzed. | The secondary outcome measures: Urinary alpha-1 microglobulin, inflammatory cytokines and C-C chemokines could not be measured due to lack of research personnel support and change in the PI who didn't have sufficient expertise to assess these measures. | Posted | Baseline and 3 months |
|
3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NAC Placebo + Silibin Placebo | N-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 months | 0 | 16 | 1 | 16 | 7 | 16 |
| EG001 | NAC Active + Silibin Placebo | N-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 months | 0 | 12 | 1 | 12 | 7 | 12 |
| EG002 | NAC Placebo + Silibin Active | N-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
| 0 | 16 | 1 | 16 | 6 | 16 |
| EG003 | NAC Active + Silibin Active | 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 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
| 0 | 16 | 1 | 16 | 8 | 16 |
| EG004 | NAC Active + High-dose Silibin Active | N-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 months | 0 | 14 | 1 | 14 | 9 | 14 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Wheezing | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Chest Pain | Cardiac disorders | Non-systematic Assessment |
| ||
| Motor Vehicle Accident | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Osteomyelitis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bradycardia | Cardiac disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Heart burn, nausea, diarrhea, abd pain, anorexia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Congestion, Sore throat, Myalgias | General disorders | Systematic Assessment |
| ||
| Infection - soft tissue, UTI | General disorders | Systematic Assessment |
| ||
| Vertigo | Nervous system disorders | Systematic Assessment |
| ||
| Hypoglycemia | Endocrine disorders | Non-systematic Assessment |
| ||
| AKI, hyperkalemia, Edema | Renal and urinary disorders | Systematic Assessment |
| ||
| Flushing | Immune system disorders | Non-systematic Assessment |
| ||
| Fracture, sprain, stiffness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Hypotension | Cardiac disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Shweta Bansal | VA- STVHCS | 2105674700 | bansals3@uthscsa.edu |
| ID | Term |
|---|---|
| D003928 | Diabetic Nephropathies |
| D011507 | Proteinuria |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D014555 | Urination Disorders |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
N-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
| OG003 | NAC Active + Silibin Active | 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 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
|
| OG004 | NAC Active + High-dose Silibin Active | N-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 months |
|
|
| OG003 | NAC Active and Silibin Active | Drug: N-acetylcysteine active and Drug: Silibin active N-acetylcysteine active and silibin active: Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 480 mg orally twice daily for three months |
| OG004 | NAC Active and High-dose Silibin Active | Drug: N-acetylcysteine active and Drug: Silibin higher dose active N-acetylcysteine active + high-dose silibin active: Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 960 mg orally twice daily for three months |
|