Study on the Effectiveness of Tranilast in the Treatment of Medium to Large Volume Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is one of the most common urinary and reproductive system diseases in elderly men. The preliminary research of the research group found that mast cells are cells that promote the progression of BPH, and the commonly used mast cell membrane stabilizer and TGF - β pathway inhibitor tranilast significantly inhibited the increase in prostate volume in animal experiments, which is considered to have potential applications in the treatment of BPH. This study plans to include 30 patients with medium to large volume BPH and experimentally explore the efficacy and safety of tranilast in the treatment of medium to large volume BPH.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Hypertrophy, Benign
• Intervention / Treatment: Drug: alpha receptor antagonist; Drug: Low dose Tranilast; Drug: High dose Tranilast

Detailed Description

Benign prostatic hyperplasia (BPH) is one of the most common urinary and reproductive system diseases in elderly men. The incidence of histological BPH in males aged 60 and above is over 50%, reaching as high as 83% at the age of 80. About 50% of BPH cases can lead to moderate to severe lower urinary tract symptoms (LUTS), and even serious complications such as hydronephrosis, which greatly affects the quality of life and health of patients, and also brings heavy social and medical burdens.

One of the important risk factors for the clinical progression of BPH is prostate volume. The risk of acute urinary retention and surgical intervention in BPH patients increased significantly with the increase of prostate volume. Medium to large volume prostate (prostate volume ≥ 60mL) is more likely to cause bladder outlet obstruction and severe hematuria, and surgical treatment is relatively difficult, with significantly increased surgical difficulty and complications. Therefore, controlling prostate volume is crucial in the treatment of benign prostatic hyperplasia.

At present, the commonly used drugs for the treatment of large volume prostate hyperplasia in clinical practice are 5 α - reductase inhibitors and α - receptor antagonists. The mechanism of action of 5 α - reductase inhibitors (such as finasteride, aprepit, etc.) is to inhibit the production of dihydrotestosterone to reduce prostate volume. However, about 40% of patients have poor reactions to these drugs, and long-term use of these drugs can lead to adverse reactions such as impaired sexual function (erectile dysfunction, decreased libido, etc.), breast discomfort, and rash. The mechanism of action of alpha receptor antagonists (such as doxazosin, tamsulosin, etc.) is to reduce urethral smooth muscle pressure and alleviate LUTS symptoms caused by BPH, but they cannot intervene in the continuous increase of prostate volume.

Quinilast is a highly effective and safe stabilizer for mast cells, TGF - β pathway inhibitor, and anti-inflammatory agent. It has a stabilizing effect on the cell membrane of mast cells and eosinophils, preventing their degranulation and inhibiting the release of histamine and 5-hydroxytryptamine allergens. It has a significant inhibitory effect on IgE antibody induced skin allergies and experimental asthma in rats. Quinilast can also inhibit collagen synthesis in fibroblasts and is currently widely used to treat allergic diseases and scars. After oral administration, the drug is rapidly absorbed in the gastrointestinal tract, with a peak plasma concentration time of 2-3 hours. It is widely distributed in all organs and tissues, with the highest concentration in the bronchi and lungs, followed by the liver, kidneys, and small intestine. The plasma half-life is 5-8.6 hours, and the blood drug concentration significantly decreases by 24 hours, making it difficult to detect after 48 hours. Metabolized in the liver, after administration, it is mainly excreted from the urine. Metabolites in the body include the demethylation product of tranilast at position 4, as well as the combination of sulfuric acid and glucuronic acid. Previous studies have confirmed that the TGF - β pathway is one of the important pathways that promote the occurrence and development of BPH. Our research confirms that the phenomenon of endothelial mesenchymal transition is an important factor in promoting the progression of BPH.

TGF - β 1 and VEGFA secreted by mast cells are important cytokines that promote endothelial mesenchymal transition in BPH, and stabilizing mast cells can inhibit endothelial cell to mesenchymal transition. The investigators confirmed through animal experiments that oral administration of tranilast (100mg/kg/d, n=10) to BPH mice for 30 consecutive days resulted in a decrease in endothelial mesenchymal transition and degree of BPH in the prostate of the mice. There was no statistically significant difference in body weight compared to the control group, and no mice died. Therefore, the investigators believe that tranilast has a promising application prospect in the treatment of BPH.

The commonly used dose of tranilast in clinical treatment of allergic diseases and scars is 100mg, three times a day (TID). There are currently no research reports on the use of tranilast for the treatment of BPH, so the effective dosage of tranilast for the treatment of BPH is not clear. Tranilast has carried out a long-term clinical trial (PRESTO test) for the treatment of atherosclerosis for more than 10000 people with a daily dose of 600mg and 900mg. The common adverse reactions (1% -10%) are nausea, abnormal liver function, and high serum creatinine. The adverse reactions will disappear after drug withdrawal. Based on our previous foundation, common dosages of tranilast, and considerations of dosage and safety in previous clinical trials, the investigators set up a low-dose group (tranilast 100mg TID) and a high-dose group (tranilast 200mg TID) in this trial to preliminarily evaluate the feasibility of applying tranilast in the clinical treatment of BPH, laying the foundation for new treatment methods for BPH in the future.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yifeng Jing; Phone Number: +86-13918839913; Email: jyf_123@163.com

Study Locations

• China
  • Shanghai, China, 200086
    • Not yet recruiting
    • Shanghai General Hospital
    • Contact: Wenqian Geng; Phone Number: +86 21 3612 6254; Email: shiyilunli@sina.com
  • Outside U.S./Canada
    • Shanghai, Outside U.S./Canada, China, 200086
      • Recruiting
      • Shanghai General Hospital
      • Contact: Tianyu Cao; Phone Number: +8618019114485; Email: kabox3@sjtu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with benign prostatic hyperplasia aged 55 to 75 years old;
• The patient's prostate volume is greater than 40mL;
• There is urinary obstruction, with an International Prostate Symptom Score (IPSS) greater than or equal to 8 points, and a maximum urinary flow rate of less than 15ml/s (urinary flow rate is not measured in patients with indwelling catheters).

Exclusion Criteria:

• Urinary disorders caused by neurogenic diseases;
• Acute urinary tract infections have not been effectively controlled;
• There are factors of lower urinary tract obstruction other than BPH, such as urethral stricture;
• History of radiation therapy or surgery in the lower urinary tract or pelvic cavity;
• Have ever suffered from tumor of urinary system, or suspected of suffering from tumor of urinary system (such as bladder cancer cancer, prostate cancer);
• Current or past liver function abnormalities (exceeding the test reference value limit);
• Abnormal renal function (exceeding the test reference value limit);
• Currently taking warfarin;
• Allergic to tranilast or drug preparations;
• Suffering from other major diseases (malignant tumors, autoimmune diseases, angina pectoris, heart failure, severe respiratory and digestive diseases, etc.), and not yet clinically cured;
• Other researchers believe that patients who are not suitable to participate in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control group	Drug: alpha receptor antagonist; Oral administration of alpha receptor antagonist (according to the dosage specified in the instructions for treating BPH)
Experimental: Low dose group	Drug: alpha receptor antagonist; Oral administration of alpha receptor antagonist (according to the dosage specified in the instructions for treating BPH); Drug: Low dose Tranilast; Oral administration of Tranilast Capsules (Qu Ke Shen, Yao Da Pharmaceutical) 100mg TID
Experimental: High dose group	Drug: alpha receptor antagonist; Oral administration of alpha receptor antagonist (according to the dosage specified in the instructions for treating BPH); Drug: High dose Tranilast; Oral administration of Tranilast Capsules (Qu Ke Shen, Yao Da Pharmaceutical) 200mg TID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate volume	No minimum and maximum values, higher scores mean a worse outcome.	The first month and the sixth month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International prostate symptom score	The minimum value is 0, and maximum values 35. Higher scores mean a worse outcome.	The first, third and sixth month
Quality of life score	The minimum value is 0, and maximum values 6. Higher scores mean a worse outcome.	The first, third and sixth month
International Index of Erectile Function	The minimum value is 0, and maximum values 25. Higher scores mean a better outcome.	The first, third and sixth month

Collaborators and Investigators

• Sponsor: Yifeng Jing

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 14, 2024

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Prostatic Hypertrophy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Hyperplasia; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Membrane Transport Modulators; Anti-Inflammatory Agents, Non-Steroidal; Platelet Aggregation Inhibitors; Anti-Allergic Agents; Calcium Channel Blockers; Histamine H1 Antagonists; tranilast
• Other Study ID Numbers: 2024HS197; 82270810 (Other Grant/Funding Number: National Natural Science Foundation of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No