Impact of Silymarin Adjunct Therapy on Proteinuria in Type 2 Diabetic Patients on RAS Inhibitors

NCT06425705 | Completed Phase 2 DMC

• 1 other identifier: LahoreGeneralH1
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Proteinuria; Type 2 Diabetes Mellitus; Renin-Angiotensin System

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Outcomes monitored after three-month.

Study Arms (2)

Group Silymarin

EXPERIMENTAL

Received 140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors.

Drug: Silymarin

Group Placebo

PLACEBO COMPARATOR

Received placebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors.

Drug: Placebo

Interventions

Silymarin DRUG

140 mg of silymarin administered orally three times daily, alongside their standard treatment with renin-angiotensin system inhibitors.

Also known as: Milk thistle extract

Group Silymarin

Placebo DRUG

placebo capsule three times a day alongside their standard treatment with renin-angiotensin system inhibitors.

Group Placebo

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Lahore General Hospital: lead

Study Sites (1)

Lahore General Hospital, Lahore

Lahore, Punjab Province, 54000, Pakistan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Proteinuria

Interventions

Silymarin; milk-thistle extract

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Muhammad Irfan Jamil, MBBS, FCPS

  Lahore General Hospital, Lahore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 22, 2024
• Study Start: February 25, 2022
• Primary Completion: July 10, 2023
• Study Completion: July 10, 2023
• Last Updated: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)