Diabetic NephropathyPhase 2NCT01003236
Evaluating the Renoprotective Effect of Milk Thistle Extract on Patients With Type II Diabetic Nephropathy
A Phase 2 study testing Milk Thistle extract in people with Diabetic Nephropathy, run by Shiraz University of Medical Sciences at 1 site in Iran.
Trial summary
There is considerable evidence that increased blood glucose results in the generation of reactive oxygen species, ultimately leading to increased oxidative stress in a variety of tissues. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- Milk Thistle extract
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteIran
- Study dates
- Oct 2010to Nov 2011
- 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type II diabetes
- Overt proteinuria defined by urinary albumin excretion > 300 mg/24 hr in 2 consecutive determinations despite treatment with highest FDA recommended doses of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker for at least 6 months.
- Treatment of hyperglycemia with (but not limited to) an oral hypoglycemic agent or insulin (If a thiazolidinedione is used, stable dose for at least 6 months)
- Treatment of hypercholesterolemia with (but not limited to) one medication from the class statins
- Presence of diabetic retinopathy
- Signing informed consent
Who cannot join
- Type I diabetes
- Advanced chronic kidney disease defined by estimated GFR < 30 ml/min/1.73 m2
- Severely uncontrolled diabetes defined by HbA1C > 10%
- Uncontrolled hypertension defined by SBP >160 mmHg or DBP >100 mmHg despite antihypertensive therapy
- Secondary forms of hypertension with defined etiology other than diabetes mellitus
- Other renal diseases
Show all 18Show fewer
- History of solid organ transplantation
- Chronic Heart Failure with NYHA class III or IV
- Active infection
- Pregnancy
- Use of one of the following medications within 2 months prior to enrollment in the study:
- Non-steroidal anti-inflammatory agents
- Antioxidants supplements including: vitamin E, vitamin C, N-acetyl- cysteine (NAC), Pentoxyfilline, Lipoic acid, Fish-oil extracts (omega-3 fatty acids), Soy extracts (isoflavones), Green-tea preparations, Pomegranate extracts, Grape extracts
- Active malignancy
- Hepatitis virus or Human Immunodeficiency virus infections
- History of drug or alcohol dependency
- Cigarette smoking
- Psychiatric or neurological condition, preventing aware consent to the study and/or adherence to the study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating the Preventive Effect of Milk Thistle Extract (Silymarin) on Progression of Diabetic Nephropathy, a Randomized, Double-blind, Placebo-controlled Clinical Trial.
There is considerable evidence that increased blood glucose results in the generation of reactive oxygen species, ultimately leading to increased oxidative stress in a variety of tissues. This may lead to the activation of stress-sensitive intracellular signaling pathways, causing cellular damage and late complications of diabetes including renal injury. Although the investigators understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. The flavonoid complex silymarin, an extract from the milk thistle, and its major pharmacological active component silibinin are free radical scavengers and potent membrane stabilizers by preventing lipid peroxidation. Furthermore, during early stages of diabetes, flavonoids minimize oxidative stress, and inflammation which represent important factors in the development of diabetic nephropathy.
In this study the investigators plan to evaluate the renoprotective effect of milk thistle extract on type II diabetic patients with kidney disease.
- Conditions
- Diabetic Nephropathy
- Being tested
- placebo, Milk Thistle extract
- Keywords
- Diabetic nephropathy, Type II Diabetes, Milk Thistle extract, Silymarin
- Medical subject headings
- Diabetic Nephropathies, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboDrug
140 mg placebo tablets, 3 times per day for 3 months
Milk Thistle extractDrug
Also called Livergol made by Goldaru Pharmaceutical Company (Iran)
1 tablet equal to 140mg silymarin administered 3 times a day for 3 months
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | 1 tablet 3 times daily Receives: Drug: placebo |
| Milk Thistle extract | Experimental | 1 tablet of the extract (equivalent to 140 mg silymarin) 3 times per day Receives: Drug: Milk Thistle extract |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in urinary albumin-creatinine ratio
Measured: 3 month
Secondary outcomes (11)
Change from baseline in urinary TNF-α
Measured: 3 month
Change from baseline in urinary TGF-β
Measured: 3 month
Change from baseline in fasting plasma glucose
Measured: 3 month
Change from baseline in blood lipid profile
Measured: 3 month
Change from baseline in hemoglobin A1C
Measured: 3 month
Change from baseline in urinary MDA
Measured: 3 month
Change from baseline in serum TNF-α
Measured: 3 month
Change from baseline in serum TGF-β
Measured: 3 month
Change from baseline in serum MDA
Measured: 3 month
Change from baseline in estimated GFR
Measured: 3 month
Change from baseline in serum creatinine
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 posted28 Oct 2009 (estimated)
- Study startOct 2010
- Primary completionOct 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathyStudies of the same condition, open and under way.
- 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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shiraz University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ghazal Vessal, Shiraz University of Medical Sciences
- Investigators
- Ghazal Vessal, PharmD, PhD, Study director, Shiraz University of Medical Sciences, Faculty of PharmacyMohammad Mehdi Sagheb, MD, Study chair, Shiraz University of Medical SciencesJamshid Roozbeh, MD, Principal investigator, Shiraz University of Medical Sciences, Nephrology Urology Research CenterMohammad Kazem Fallahzadeh Abarghouei, M.D., Principal investigator, Shiraz University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01003236
- Sponsor's protocol ID
- 4774
- Status last verified
- Jun 2012
- First submitted
- 27 Oct 2009
- Last updated
- 25 Jun 2012
- 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 37916745Fallahzadeh MK, Dormanesh B, Sagheb MM, Roozbeh J, Vessal G, Pakfetrat M, Daneshbod Y, Kamali-Sarvestani E, Lankarani KB. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic patients with overt nephropathy: a randomized, double-blind, placebo-controlled trial. Am J Kidney Dis. 2012 Dec;60(6):896-903. doi: 10.1053/j.ajkd.2012.06.005. Epub 2012 Jul 7.
PubMed 22770926
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Preventive Effect of Milk Thistle Extract (Silymarin) on Progression of Diabetic Nephropathy, a Randomized, Double-blind, Placebo-controlled Clinical Trial.
- ClinicalTrials.gov ID
- NCT01003236
- Acronym / sponsor ID
- 4774
- Conditions
- Diabetic Nephropathy
- Keywords
- Diabetic nephropathy, Type II Diabetes, Milk Thistle extract, Silymarin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Shiraz University of Medical SciencesUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 28 Oct 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.
There is considerable evidence that increased blood glucose results in the generation of reactive oxygen species, ultimately leading to increased oxidative stress in a variety of tissues. This may lead to the activation of stress-sensitive intracellular signaling pathways, causing cellular damage and late complications of diabetes including renal injury. Although the investigators understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. The flavonoid complex silymarin, an extract from the milk thistle, and its major pharmacological active component silibinin are free radical scavengers and potent membrane stabilizers by preventing lipid peroxidation. Furthermore, during early stages of diabetes, flavonoids minimize oxidative stress, and inflammation which represent important factors in the development of diabetic nephropathy.
In this study the investigators plan to evaluate the renoprotective effect of milk thistle extract on type II diabetic patients with kidney disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: placebo1 tablet 3 times daily |
| Milk Thistle extract | Experimental | Drug: Milk Thistle extract1 tablet of the extract (equivalent to 140 mg silymarin) 3 times per day |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Type II diabetes
- Overt proteinuria defined by urinary albumin excretion > 300 mg/24 hr in 2 consecutive determinations despite treatment with highest FDA recommended doses of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker for at least 6 months.
- Treatment of hyperglycemia with (but not limited to) an oral hypoglycemic agent or insulin (If a thiazolidinedione is used, stable dose for at least 6 months)
- Treatment of hypercholesterolemia with (but not limited to) one medication from the class statins
- Presence of diabetic retinopathy
Key exclusion criteria (18 listed)
- Type I diabetes
- Advanced chronic kidney disease defined by estimated GFR < 30 ml/min/1.73 m2
- Severely uncontrolled diabetes defined by HbA1C > 10%
- Uncontrolled hypertension defined by SBP >160 mmHg or DBP >100 mmHg despite antihypertensive therapy
- Secondary forms of hypertension with defined etiology other than diabetes mellitus
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 |
|---|---|---|
| placebo140 mg placebo tablets, 3 times per day for 3 months | Drug | placebo |
| Milk Thistle extractAlso: Livergol made by Goldaru Pharmaceutical Company (Iran)1 tablet equal to 140mg silymarin administered 3 times a day for 3 months | Drug | Milk Thistle extract |
Primary outcome
Change from baseline in urinary albumin-creatinine ratio
Time frame: 3 month
11 secondary outcomes
Change from baseline in urinary TNF-α
Time frame: 3 month
Change from baseline in urinary TGF-β
Time frame: 3 month
Change from baseline in fasting plasma glucose
Time frame: 3 month
Change from baseline in blood lipid profile
Time frame: 3 month
Change from baseline in hemoglobin A1C
Time frame: 3 month
Change from baseline in urinary MDA
Time frame: 3 month
Change from baseline in serum TNF-α
Time frame: 3 month
Change from baseline in serum TGF-β
Time frame: 3 month
Change from baseline in serum MDA
Time frame: 3 month
Change from baseline in estimated GFR
Time frame: 3 month
Change from baseline in serum creatinine
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 25 Jun 2012.
- 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.
- Derived from this study: PubMed 22770926Fallahzadeh MK, Dormanesh B, Sagheb MM, Roozbeh J, Vessal G, Pakfetrat M, Daneshbod Y, Kamali-Sarvestani E, Lankarani KB. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic patients with overt nephropathy: a randomized, double-blind, placebo-controlled trial. Am J Kidney Dis. 2012 Dec;60(6):896-903. doi: 10.1053/j.ajkd.2012.06.005. Epub 2012 Jul 7.
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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.
Ghazal Vessal, PharmD, PhD study director
Shiraz University of Medical Sciences, Faculty of Pharmacy
Mohammad Mehdi Sagheb, MD study chair
Shiraz University of Medical Sciences
Jamshid Roozbeh, MD principal investigator
Shiraz University of Medical Sciences, Nephrology Urology Research Center
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 Milk Thistle extract in people with Diabetic Nephropathy, run by Shiraz University of Medical Sciences at 1 site in Iran.
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 6 inclusion and 18 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 25 Jun 2012. 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 Iran. 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?
Change from baseline in urinary albumin-creatinine ratio (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 NCT01003236, which also lists 2 linked publications.
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 25 Jun 2012.