Diabetic NephropathiesPhase 2NCT00915200
N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy
A Phase 2 study testing N-acetylcysteine, silibin and high-dose silibin in people with Diabetic Nephropathies and Proteinuria, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetic Nephropathies, Proteinuria, Oxidative Stress
- What is being tested?
- N-acetylcysteine, silibin and high-dose silibin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Apr 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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:
Show all 25Show fewer
- 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;
- 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, and 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Hlth Sci Ctr San Ant
San Antonio, Texas, 78229
About this study
Official title: N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy.
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.
Read the detailed description
Oxidative stress and 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 type 2 diabetes mellitus and related nephropathy. We 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 glutathione (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.
- Conditions
- Diabetic Nephropathies, Proteinuria, Oxidative Stress
- Being tested
- N-acetylcysteine, silibin, high-dose silibin, N-acetylcysteine placebo, silibin placebo
- Keywords
- Diabetic Nephropathies, Proteinuria, Renal Insufficiency, Chronic, Monocytes, Oxidative stress, Inflammation, Antioxidants, Glutathione, Silymarin, Acetylcysteine, Dietary Supplements, Complementary Therapies
- Medical subject headings
- Diabetic Nephropathies, Proteinuria, Renal Insufficiency, Chronic, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDietary supplement
Also called NAC
600 mg orally twice daily for three months
silibinDietary supplement
Also called silibin-phosphatidylcholine, Siliphos
480 mg orally twice daily for three months
high-dose silibinDietary supplement
Also called silibin-phosphatidylcholine, Siliphos
960 mg orally twice daily for three months
N-acetylcysteine placeboDietary supplement
Also called NAC placebo
excipient orally twice daily for three months
silibin placeboDietary supplement
Also called silibin-phosphatidylcholine placebo, Siliphos placebo
excipient orally twice daily for three months
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | N-acetylcysteine placebo + silibin placebo Receives: Dietary Supplement: N-acetylcysteine placebo; Dietary Supplement: silibin placebo |
| N-acetylcysteine | Experimental | N-acetylcysteine active + silibin placebo Receives: Dietary Supplement: N-acetylcysteine; Dietary Supplement: silibin placebo |
| silibin | Experimental | N-acetylcysteine placebo + silibin active Receives: Dietary Supplement: silibin; Dietary Supplement: N-acetylcysteine placebo; Dietary Supplement: silibin placebo |
| N-acetycysteine + silibin | Experimental | N-acetylcysteine active + silibin active Receives: Dietary Supplement: N-acetylcysteine; Dietary Supplement: silibin; Dietary Supplement: silibin placebo |
| N-acetylcysteine + high-dose silibin | Experimental | N-acetylcysteine active + high-dose silibin active Receives: Dietary Supplement: N-acetylcysteine; Dietary Supplement: high-dose silibin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary Albumin excretion
Measured: 3-month
Secondary outcomes (4)
urinary alpha-1 microglobulin excretion
Measured: 3-month
urinary C-C-chemokines excretion
Measured: 3-month
peripheral blood monocyte glutathione content
Measured: 3-month
tolerance and safety
Measured: 3-month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2009 (estimated)
- Study startOct 2009
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathiesStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), VA Office of Research and Development
- Responsible party
- Sponsor
- Investigators
- Paolo Fanti, M.D., Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00915200
- Sponsor's protocol ID
- NIH 1R21AT004490
- Other IDs
- 1I01CX000264-01A2, R21AT004490
- Status last verified
- Jun 2016
- First submitted
- 2 Jun 2009
- Last updated
- 27 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37916745
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy.
- ClinicalTrials.gov ID
- NCT00915200
- Acronym / sponsor ID
- NIH 1R21AT004490
- Conditions
- Diabetic Nephropathies, Proteinuria, Oxidative Stress
- Keywords
- Diabetic Nephropathies, Proteinuria, Renal Insufficiency, Chronic, Monocytes, Oxidative stress, Inflammation, Antioxidants, Glutathione
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), VA Office of Research and Development
- Study start
- Oct 2009
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 5 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Oxidative stress and 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 type 2 diabetes mellitus and related nephropathy. We 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 glutathione (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: N-acetylcysteine placebo, Dietary Supplement: silibin placeboN-acetylcysteine placebo + silibin placebo |
| N-acetylcysteine | Experimental | Dietary Supplement: N-acetylcysteine, Dietary Supplement: silibin placeboN-acetylcysteine active + silibin placebo |
| silibin | Experimental | Dietary Supplement: silibin, Dietary Supplement: N-acetylcysteine placebo, Dietary Supplement: silibin placeboN-acetylcysteine placebo + silibin active |
| N-acetycysteine + silibin | Experimental | Dietary Supplement: N-acetylcysteine, Dietary Supplement: silibin, Dietary Supplement: silibin placeboN-acetylcysteine active + silibin active |
| N-acetylcysteine + high-dose silibin | Experimental | Dietary Supplement: N-acetylcysteine, Dietary Supplement: high-dose silibinN-acetylcysteine active + high-dose silibin active |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males or females, age 18-70 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) one diuretic, one beta- blocker and one medication from the classes ARBs or ACE inhibitors.
Key exclusion criteria (25 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NAC600 mg orally twice daily for three months | Dietary supplement | N-acetycysteine + silibin, N-acetylcysteine, N-acetylcysteine + high-dose silibin |
| silibinAlso: silibin-phosphatidylcholine, Siliphos480 mg orally twice daily for three months | Dietary supplement | N-acetycysteine + silibin, silibin |
| high-dose silibinAlso: silibin-phosphatidylcholine, Siliphos960 mg orally twice daily for three months | Dietary supplement | N-acetylcysteine + high-dose silibin |
| N-acetylcysteine placeboAlso: NAC placeboexcipient orally twice daily for three months | Dietary supplement | Placebo, silibin |
| silibin placeboAlso: silibin-phosphatidylcholine placebo, Siliphos placeboexcipient orally twice daily for three months | Dietary supplement | N-acetycysteine + silibin, N-acetylcysteine, Placebo, silibin |
Primary outcome
Urinary Albumin excretion
Time frame: 3-month
4 secondary outcomes
urinary alpha-1 microglobulin excretion
Time frame: 3-month
urinary C-C-chemokines excretion
Time frame: 3-month
peripheral blood monocyte glutathione content
Time frame: 3-month
tolerance and safety
Time frame: 3-month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2016.
- Derived from this study: PubMed 37916745Colombijn 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paolo Fanti, M.D. principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetylcysteine, silibin and high-dose silibin in people with Diabetic Nephropathies and Proteinuria, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urinary Albumin excretion (time frame: 3-month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00915200, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2016.