Naoxintong Capsule for Diabetic Nephropathy With Dampness Retention Pattern: A Multicenter, Randomized, Double-Blind, Placebo-Controlled TrialAcronymNXT-DKD

NCT07698223 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: NXT-DKD-2026-001
• Study Type: interventional
• Target: 410
• Locations: 1 country
• Sites: 8

Brief Summary

Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease worldwide and is associated with a high risk of cardiovascular events and mortality. Despite current standard therapies including renin-angiotensin system inhibitors (ACEI/ARB), glycemic control, and blood pressure management, disease progression remains inadequately controlled in many patients. Naoxintong Capsule is a traditional Chinese medicine formulation composed of 16 herbal ingredients (Astragalus membranaceus, Prunus persica seed, Carthamus tinctorius, Paeonia lactiflora, Angelica sinensis, Ligusticum chuanxiong, Boswellia carterii, Commiphora myrrha, Salvia miltiorrhiza, Achyranthes bidentata, Cinnamomum cassia, Morus alba, Spatholobus suberectus, Buthus martensii, Pheretima aspergillum, and Hirudo nipponica). It has been widely used in China for cardiovascular and cerebrovascular diseases, with demonstrated effects on endothelial protection, anti-inflammation, anti-thrombosis, and plaque stabilization. This multicenter, randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy and safety of Naoxintong Capsule added to standard conventional therapy in slowing the progression of diabetic nephropathy and providing cardiovascular protection. A total of 410 patients with Type 2 diabetic nephropathy will be randomized (1:1) to receive either Naoxintong Capsules (4 capsules, 3 times daily) or matching placebo, in addition to standard therapy, for 12 months. The primary outcome is the annual rate of decline in estimated glomerular filtration rate (eGFR). Secondary outcomes include changes in proteinuria, CKD stage progression, time to end-stage kidney disease, major adverse cardiovascular events, TCM syndrome scores, and quality of life measures.

Conditions

Diabetic Nephropathy

Keywords

Diabetic Kidney Disease; Diabetic Nephropathy; Naoxintong Capsule; Traditional Chinese Medicine; Dampness Retention Pattern; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (3)

• Annual Rate of Decline in Estimated Glomerular Filtration Rate (eGFR)

  The annual rate of decline in eGFR (ml/min/1.73m\^2/year), calculated as the slope of eGFR over the 12-month treatment period using all available eGFR measurements at each scheduled visit. eGFR is estimated using the CKD-EPI equation. A less negative slope indicates slower disease progression.

  Baseline to Month 12

• Change in 24-Hour Urinary Protein Excretion From Baseline

  Change from baseline in 24-hour urinary protein excretion (g/24h), measured at each scheduled visit. A decrease indicates renal protective effect.

  Baseline to Month 12

• Renal Composite Endpoint: eGFR Decline >30%, ESKD, or MACE

  Time to first occurrence of: sustained eGFR decline \>30% from baseline; end-stage kidney disease; or major adverse cardiovascular event.

  From randomization through Month 12

Secondary Outcomes (9)

• Proportion of Participants With CKD Stage Improvement, Stabilization, or Progression

  Baseline to Month 12

• Time to Sustained eGFR Decline of Greater Than 30% From Baseline

  From randomization through Month 12

• Time to End-Stage Kidney Disease (ESKD)

  From randomization through Month 12

• Time to First Unplanned Hospitalization for Heart Failure

  From randomization through Month 12

• Time to First Non-Fatal Myocardial Infarction

  From randomization through Month 12

Study Arms (2)

Naoxintong Capsule Group

EXPERIMENTAL

Participants will receive Naoxintong Capsules (4 capsules per dose, 3 times daily, orally, 30-60 minutes after meals) in addition to standard conventional therapy for diabetic nephropathy, for a total treatment duration of 12 months. Standard conventional therapy includes glycemic control (oral hypoglycemic agents and/or insulin), blood pressure management (ACEI or ARB, with optional non-RASI antihypertensives), lipid-lowering therapy (statins as indicated), dietary management (protein 0.6-0.8 g/kg/day, sodium \<3 g/day), and treatment of CKD-related complications as clinically indicated.

Drug: Naoxintong Capsule

Placebo Group

PLACEBO COMPARATOR

Participants will receive matching placebo capsules (4 capsules per dose, 3 times daily, orally, 30-60 minutes after meals) in addition to standard conventional therapy for diabetic nephropathy, for a total treatment duration of 12 months. Standard conventional therapy is identical to that provided in the Naoxintong group.

Drug: Placebo

Interventions

Naoxintong Capsule DRUG

Naoxintong Capsule is a traditional Chinese medicine formulation composed of 16 herbal and animal-derived ingredients: Astragalus membranaceus (Huangqi), Prunus persica seed (Taoren), Carthamus tinctorius flower (Honghua), Paeonia lactiflora root (Chishao), Angelica sinensis root (Danggui), Ligusticum chuanxiong rhizome (Chuanxiong), Boswellia carterii resin (Ruxiang), Commiphora myrrha resin (Moyao), Salvia miltiorrhiza root (Danshen), Achyranthes bidentata root (Niuxi), Cinnamomum cassia twig (Guizhi), Morus alba twig (Sangzhi), Spatholobus suberectus stem (Jixueteng), Buthus martensii (Quanxie), Pheretima aspergillum (Dilong), and Hirudo nipponica (Shuizhi). Each capsule contains 0.4 g of active ingredients. Dosage: 4 capsules (1.6 g) per dose, taken orally 3 times daily, 30-60 minutes after meals. Manufactured by Shaanxi Buchang Pharmaceutical Co., Ltd. (National Drug Approval No.: Guoyaozhunzi Z20025001). Storage: sealed, at room temperature. Shelf life: 24 months.

Naoxintong Capsule Group

Placebo DRUG

Matching placebo capsules identical in appearance, size, shape, color, weight, packaging, and labeling to Naoxintong Capsules but containing no active pharmaceutical or herbal ingredients. Dosage: 4 capsules per dose, taken orally 3 times daily, 30-60 minutes after meals. Manufactured by Shaanxi Buchang Pharmaceutical Co., Ltd. Storage: sealed, at room temperature. Shelf life: 24 months.

Placebo Group

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years.
• Meets the diagnostic criteria for Type 2 diabetic nephropathy, defined as:
• Confirmed diagnosis of Type 2 diabetes mellitus; AND
• At least one of the following: urinary albumin-to-creatinine ratio (UACR) \>= 30 mg/g, or eGFR \< 60 mL/min/1.73m\^2, confirmed by repeat testing (interval \>= 3 months), after excluding transient factors such as acute kidney injury, dehydration, infection, or heart failure; OR
• Renal biopsy confirmed as isolated diabetic nephropathy; AND
• hour urinary protein excretion \>= 0.5 g and \< 3.5 g.
• Estimated glomerular filtration rate (eGFR) \>= 45 mL/min/1.73m\^2.
• On a stable dose of ACE inhibitor (ACEI) or Angiotensin II receptor blocker (ARB) therapy for at least 8 weeks prior to enrollment. If SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRA), or GLP-1 receptor agonists are being used, the dose must have been stable for at least 4 weeks prior to enrollment and remain unchanged during the study period. Patients not currently using these agents must not initiate them during the study.
• Signed informed consent form.

You may not qualify if:

• Type 1 diabetes mellitus or other types of diabetes mellitus (e.g., secondary diabetes, maturity-onset diabetes of the young).
• Coexisting systemic autoimmune or immune-mediated disease where the clinical assessment suggests a non-diabetic nephropathy etiology.
• Decline in eGFR of \> 30% within the past 3 months.
• Persistent serum potassium \> 5.5 mmol/L.
• Diagnosis of hemorrhagic cardiovascular or cerebrovascular disease within the past 3 months.
• Known allergy or hypersensitivity to any component of Naoxintong Capsule or placebo; pregnant or lactating women.
• Participation in another drug or medical device clinical trial within the past 6 months.
• Any other condition that, in the investigator's judgment, renders the patient unsuitable for participation in the clinical trial (e.g., severe hepatic dysfunction, life expectancy \< 1 year).

Sponsors & Collaborators

• Chen Xiangmei: lead

Study Sites (8)

Chinese PLA General Hospital, First Medical Center

Beijing, Beijing Municipality, 100853, China

Location

China-Japan Friendship Hospital

Beijing, Beijing Municipality, China

Location

Daping Hospital, Army Medical University

Chongqing, Chongqing Municipality, China

Location

First Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

Location

Longhua Hospital, Shanghai University of Traditional Chinese Medicine

Shanghai, Shanghai Municipality, China

Location

Renji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Location

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Location

Zhejiang Provincial Hospital of Traditional Chinese Medicine

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

naoxintong

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Central Study Contacts

Zheyi Dong, MD

CONTACT

010-66937763; shengdai26@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study. Both the participants and the investigators are blinded to treatment assignment. Naoxintong Capsules and matching placebo capsules are identical in appearance, size, color, packaging, and labeling. The randomization code is maintained by the central data management center and will not be disclosed to investigators or participants until database lock, except in emergency situations requiring unblinding for safety reasons. Emergency unblinding envelopes are provided to each study site.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 13, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: After publication of primary results
• Access Criteria: Via reasonable request with data use agreement

Locations

CN (8)