Type 2 Diabetes MellitusPhase 2NCT06425705
Impact of Silymarin Adjunct Therapy on Proteinuria in Type 2 Diabetic Patients on RAS Inhibitors
A Phase 2 study testing Silymarin in people with Type 2 Diabetes Mellitus, run by Lahore General Hospital at 1 site in Pakistan.
Trial summary
Given the inadequacies of existing pharmacological interventions for diabetic nephropathy, this study is predicated on the hypothesis that silymarin, having shown promise in mitigating hyperglycemia in diabetic patients without nephropathy and displaying renal protective effects in animal models, merits a thorough and… Read more about this study
- Who is it for?
- Ages 35 to 70 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Silymarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 sitePakistan
- Study dates
- 25 Feb 2022to 10 Jul 2023
- 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 35 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 35-70 years.
- Both male and female with 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 SGLT2 inhibitors is used, stable dose for at least 3 months).
- Treatment of hypercholesterolemia with (but not limited to) one medication from the class statins.
- Patients using stable dose of Non-Dihydropyridine Calcium Channel Blockers for at least 6 months as antihypertensive.
- 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 >140 mmHg or DBP >90 mmHg despite antihypertensive therapy.
- Patients with organ transplant history.
- Secondary forms of hypertension with defined etiology other than diabetes mellitus.
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- Other renal diseases.
- 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), Pentoxifylline, Lipoic acid, Fish-oil extracts (omega-3 fatty acids), Soy extracts (isoflavones), Green-tea preparations, Pomegranate extracts, Grape extracts.
- 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.
Trial locations and contacts
1 site in 1 country.
Pakistan1 site
Lahore General Hospital, Lahore
Lahore, Punjab Province, 54000
About this study
Official title: Evaluating the Outcome of Silymarin as an Adjunct Therapy to Renin-Angiotensin System Inhibitors in Proteinuric Type 2 Diabetic Patients
Given the inadequacies of existing pharmacological interventions for diabetic nephropathy, this study is predicated on the hypothesis that silymarin, having shown promise in mitigating hyperglycemia in diabetic patients without nephropathy and displaying renal protective effects in animal models, merits a thorough and systematic investigation. The current body of research on silymarin, particularly human trials, is limited by small cohorts and the preliminary nature of its outcomes. This research aims to evaluate the efficacy of silymarin as an adjunctive treatment in patients with Type 2 diabetes mellitus (T2DM) already on renin-angiotensin system inhibitors, focusing on its potential to reduce proteinuria and improve renal function. The ultimate objective is to amass more definitive evidence that could potentially inform a new therapeutic approach in the management of diabetic nephropathy.
Read the detailed description
After securing the approval from the Ethical Review Board of hospital, this study was conducted in the Nephrology Department, Lahore General Hospital, Lahore. All patients diagnosed with Type 2 Diabetes Mellitus was assessed based on the previously defined inclusion and exclusion criteria. Informed consent was obtained from all eligible participants who agreed to participate in the study.
Baseline Data Collection: Upon enrollment, demographic and clinical information including age, gender, duration of diabetes, baseline renal function tests, current medication use, and baseline measures of HBA1c, FBS, RBS and proteinuria were collected. This information was provided a comprehensive profile of each participant at the start of the study.
Treatment Allocation: Patients was randomly assigned into two groups using a lottery method:
- Group A: received 140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors.
- Group B: received placebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors.
Monitoring and Follow-up Assessments: Participants was assessed for outcomes after at one month and 3 months to monitor changes in proteinuria and renal function. Specific tests were included:
- Measurement of Urinary Albumin-Creatinine Ratio (UACR): Participants were required to provide 24-hour urine specimens at one month and three months into the study. To ensure that the urine samples are not affected by external factors, patients was instructed to maintain their usual physical activities and avoid strenuous exercises the evening before the assessment days. Proteinuria was quantified using immunoturbidimetry.
- Assessment of Serum Creatinine and Calculation of eGFR to Monitor Renal Function: The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula at one month and three months. These assessments were help to monitor any changes in renal function over the course of the study.
- Measurement of HbA1c levels after 3 months. The data was recorded meticulously using standardized data collection forms. Data was analyzed using SPSS version 26.0. Baseline characteristics of participants (age, gender, duration of diabetes, baseline renal function tests, HbA1c, FBS, RBS) were summarized using means and standard deviations for continuous variables, and frequencies and percentages for categorical variables. Changes in UACR, eGFR, and HbA1c from baseline to one month and three months were compared between Group A (silymarin) and Group B (placebo) using independent t-tests or Mann-Whitney U tests, depending on the normality of the data. Analysis of Covariance (ANCOVA) was used to adjust for any baseline imbalances and potential confounders between the two groups. Repeated measures ANOVA were employed to analyze changes over time within and between treatment groups for UACR, eGFR, and HbA1c levels, accounting for within-subject correlation over the assessment periods. All statistical tests were two-sided, and a p-value of less than 0.05 was considered statistically significant.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Silymarin, Placebo
- Keywords
- Proteinuria, Type 2 Diabetes Mellitus, Renin-Angiotensin System
- Medical subject headings
- Diabetes Mellitus, Type 2, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SilymarinDrug
Also called Milk thistle extract
140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors.
PlaceboDrug
placebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors.
| Study group | Role | What they receive |
|---|---|---|
| Group Silymarin | Experimental | Received 140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors. Receives: Drug: Silymarin |
| Group Placebo | Placebo comparator | Received placebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the urinary albumin-creatinine ratio (UACR) from baseline
It was measured quantitatively by comparing the urinary albumin-creatinine ratio (UACR) in mg/g between initial recruitment and subsequent follow-up visits at one and three months.
Measured: Outcomes monitored at one and three-month intervals
Change in estimated glomerular filtration rate (eGFR) from baseline
eGFR was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula, which incorporates serum creatinine, age, sex, and race. The outcome measure was the change in eGFR in mL/min/1.73 m² at one month and three months compared to the baseline value.
Measured: Outcomes monitored at one and three-month intervals
Change in HbA1c levels from baseline
It was measured quantitatively by comparing the HbA1c levels in percentage (%) between initial recruitment and subsequent follow-up visit after three months.
Measured: Outcomes monitored after three-month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2024
- Study start25 Feb 2022
- Primary completion10 Jul 2023
- Study completion10 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lahore General Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Muhammad Irfan Jamil, Lahore General Hospital
- Investigators
- Muhammad Irfan Jamil, MBBS, FCPS, Principal investigator, Lahore General Hospital, Lahore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06425705
- Sponsor's protocol ID
- LahoreGeneralH1
- Status last verified
- May 2024
- First submitted
- 7 May 2024
- Last updated
- 22 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: will be shared on special request
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Outcome of Silymarin as an Adjunct Therapy to Renin-Angiotensin System Inhibitors in Proteinuric Type 2 Diabetic Patients
- ClinicalTrials.gov ID
- NCT06425705
- Acronym / sponsor ID
- LahoreGeneralH1
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Proteinuria, Type 2 Diabetes Mellitus, Renin-Angiotensin System
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Lahore General HospitalOther government
- Study start
- 25 Feb 2022 (actual)
- Primary completion
- 10 Jul 2023 (actual)
- Study completion
- 10 Jul 2023 (actual)
- First posted
- 22 May 2024 (actual)
- 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.
Given the inadequacies of existing pharmacological interventions for diabetic nephropathy, this study is predicated on the hypothesis that silymarin, having shown promise in mitigating hyperglycemia in diabetic patients without nephropathy and displaying renal protective effects in animal models, merits a thorough and systematic investigation. The current body of research on silymarin, particularly human trials, is limited by small cohorts and the preliminary nature of its outcomes. This research aims to evaluate the efficacy of silymarin as an adjunctive treatment in patients with Type 2 diabetes mellitus (T2DM) already on renin-angiotensin system inhibitors, focusing on its potential to reduce proteinuria and improve renal function. The ultimate objective is to amass more definitive evidence that could potentially inform a new therapeutic approach in the management of diabetic nephropathy.
Detailed description
After securing the approval from the Ethical Review Board of hospital, this study was conducted in the Nephrology Department, Lahore General Hospital, Lahore. All patients diagnosed with Type 2 Diabetes Mellitus was assessed based on the previously defined inclusion and exclusion criteria. Informed consent was obtained from all eligible participants who agreed to participate in the study.
Baseline Data Collection: Upon enrollment, demographic and clinical information including age, gender, duration of diabetes, baseline renal function tests, current medication use, and baseline measures of HBA1c, FBS, RBS and proteinuria were collected. This information was provided a comprehensive profile of each participant at the start of the study.
Treatment Allocation: Patients was randomly assigned into two groups using a lottery method:
- Group A: received 140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors.
- Group B: received placebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors.
Monitoring and Follow-up Assessments: Participants was assessed for outcomes after at one month and 3 months to monitor changes in proteinuria and renal function. Specific tests were included:
- Measurement of Urinary Albumin-Creatinine Ratio (UACR): Participants were required to provide 24-hour urine specimens at one month and three months into the study. To ensure that the urine samples are not affected by external factors, patients was instructed to maintain their usual physical activities and avoid strenuous exercises the evening before the assessment days. Proteinuria was quantified using immunoturbidimetry.
- Assessment of Serum Creatinine and Calculation of eGFR to Monitor Renal Function: The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula at one month and three months. These assessments were help to monitor any changes in renal function over the course of the study.
- Measurement of HbA1c levels after 3 months. The data was recorded meticulously using standardized data collection forms. Data was analyzed using SPSS version 26.0. Baseline characteristics of participants (age, gender, duration of diabetes, baseline renal function tests, HbA1c, FBS, RBS) were summarized using means and standard deviations for continuous variables, and frequencies and percentages for categorical variables. Changes in UACR, eGFR, and HbA1c from baseline to one month and three months were compared between Group A (silymarin) and Group B (placebo) using independent t-tests or Mann-Whitney U tests, depending on the normality of the data. Analysis of Covariance (ANCOVA) was used to adjust for any baseline imbalances and potential confounders between the two groups. Repeated measures ANOVA were employed to analyze changes over time within and between treatment groups for UACR, eGFR, and HbA1c levels, accounting for within-subject correlation over the assessment periods. All statistical tests were two-sided, and a p-value of less than 0.05 was considered statistically significant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group Silymarin | Experimental | Drug: SilymarinReceived 140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors. |
| Group Placebo | Placebo comparator | Drug: PlaceboReceived placebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors. |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients aged 35-70 years.
- Both male and female with 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 SGLT2 inhibitors is used, stable dose for at least 3 months).
- Treatment of hypercholesterolemia with (but not limited to) one medication from the class statins.
Key exclusion criteria (16 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 >140 mmHg or DBP >90 mmHg despite antihypertensive therapy.
- Patients with organ transplant history.
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 |
|---|---|---|
| SilymarinAlso: Milk thistle extract140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors. | Drug | Group Silymarin |
| Placeboplacebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors. | Drug | Group Placebo |
Primary outcome
Change in the urinary albumin-creatinine ratio (UACR) from baseline
Time frame: Outcomes monitored at one and three-month intervals
It was measured quantitatively by comparing the urinary albumin-creatinine ratio (UACR) in mg/g between initial recruitment and subsequent follow-up visits at one and three months.
Change in estimated glomerular filtration rate (eGFR) from baseline
Time frame: Outcomes monitored at one and three-month intervals
eGFR was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula, which incorporates serum creatinine, age, sex, and race. The outcome measure was the change in eGFR in mL/min/1.73 m² at one month and three months compared to the baseline value.
Change in HbA1c levels from baseline
Time frame: Outcomes monitored after three-month.
It was measured quantitatively by comparing the HbA1c levels in percentage (%) between initial recruitment and subsequent follow-up visit after three months.
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 22 May 2024.
- Individual participant dataSharing planned: No. will be shared on special request
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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.
Muhammad Irfan Jamil, MBBS, FCPS principal investigator
Lahore General Hospital, Lahore
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 Silymarin in people with Type 2 Diabetes Mellitus, run by Lahore General Hospital at 1 site in Pakistan.
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 8 inclusion and 16 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 22 May 2024. 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 Pakistan. 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 in the urinary albumin-creatinine ratio (UACR) from baseline (time frame: Outcomes monitored at one and three-month intervals). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2024.