Clinical Study of Treating Type 2 Diabetic Nephropathy With Alfacalcidol and Irbesartan

A Prospective, Multi-center, Randomized, Open-label, Parallel-arm Controlled Study of Treating Type 2 Diabetic Nephropathy (Stage II-IV) With Alfacalcidol and Irbesartan

This is a prospective, multi-center, randomized, open-label, parallel-arm controlled study, for which a total of 216 patients with type 2 diabetic nephropathy (Stage II-IV) will be enrolled. The subjects will be randomized to three groups in 1:1:1 ratio. One group receive Alfacalcidol 0.25ug/day and Irbesartan 150mg/day for 16 consecutive weeks. The second group receive Alfacalcidol 0.25ug/day alone for 16 consecutive weeks. The third group receive Irbesartan 150mg/day alone for 16 consecutive weeks. All subjects will be followed up for 4 weeks after medication is over. A total of 4 visits have been scheduled for this study at week 0, week 8, week 16, week 20.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetic Nephropathy
• Intervention / Treatment: Drug: Irbesartan; Drug: Alfacalcidol

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • The Third Xiangya Hospital of Central South University
    • Chenzhou, Hunan, China, 423000
      • Hunan Chenzhou NO.1 People's Hospital
    • Yiyang, Hunan, China, 413000
      • Hunan Yiyang Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult Chinese subjects, at age 18-65, diagnosed with Type 2 diabetic nephropathy (Stage II-IV) who meet the WHO diagnostic standards of diabetes in 1999. The international Mogensen staging standard for diabetic nephropathy is used. Specifically, in Stage II (normal albuminuria stage), the UAER is normal (<20μg /min or<30mg/24h). In Stage III (early diabetic nephropathy stage), the UAER is 20-200μg /min or 30-300 mg/24h. In Stage IV (clinical or overt diabetic nephropathy stage), the UAER is >200μg/min or urine protein quantitation is >500mg /24h.

Exclusion Criteria:

• Renal damage caused by other causes;
• Uncontrolled hypertension (blood pressure constantly greater than 140/ 90mmHg);
• Type 1 Diabetes
• Any acute and chronic infections;
• Glycosylated hemoglobin (HbA1c)>7.5%;
• 24h urinary protein quantity>3g, serum albumin<25g /L and estimated glomerular filtration rate (eGFR)<60 ml/min;
• Patients who suffered from malignant tumors or any illness that endanger life, such as liver, kidney, heart and lung function insufficiency over the past 5 years;
• People who have received the gastrointestinal operation, which may affect absorption of Vitamin D;
• People who have taken such drugs as angiotensin receptor blocker, calcium, and angiotensin converting enzyme inhibitor that affect excretion of urine protein, and who have been allergic to Vitamin D;
• Pregnant or lactating women;
• Other candidates that are deemed not suitable by investigators.

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: Alfacalcidol and Irbesartan; The subjects in this group orally take Alfacalcidol Soft Capsules at 0.25ug/day and Irbesartan Pills at 150mg/day for 16 consecutive weeks.All subjects will be followed up for 4 weeks after medication is over. A total of 4 visits have been scheduled for this study at week 0, week 8, week 16, week 20.	Drug: Irbesartan; Other Names: Irbesartan Pills; Drug: Alfacalcidol; Other Names: Alfacalcidol Soft Capsules
Active Comparator: Irbesartan; The subjects in this group orally take Irbesartan Pills at 150mg/day for 16 consecutive weeks.All subjects will be followed up for 4 weeks after medication is over. A total of 4 visits have been scheduled for this study at week 0, week 8, week 16, week 20.	Drug: Irbesartan; Other Names: Irbesartan Pills
Active Comparator: Alfacalcidol; The subjects in this group orally takeAlfacalcidol Soft Capsules at 0.25ug/day for 16 consecutive weeks.All subjects will be followed up for 4 weeks after medication is over. A total of 4 visits have been scheduled for this study at week 0, week 8, week 16, week 20.	Drug: Alfacalcidol; Other Names: Alfacalcidol Soft Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in 24h urinary albumin excretion rate (UAER) by comparing visits at week 20 with the baseline	at Week 20
Changes in 24h urinary protein quantity by comparing visits at week 20 with the baseline	at Week 20

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in estimated glomerular filtration rate (eGFR) by comparing visits at week 20 with the baseline	at Week 20
Changes in the urine levels of IL-6, MCP-1, TGF-β1, MIP-1β, and PTPN2 by comparing visits at week 20 with the baseline.	at Week 20
Changes in serum levels of IL-6, MCP-1, TGF-β1, MIP-1β, and PTPN2 by comparing visits at week 20 with the baseline.	at Week 20
Changes in urinary albumin / creatinine (UACR) of morning urine by comparing visits at week 20 with the baseline	at Week 20

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of all adverse events (AEs) and serious adverse events (SAEs)	during the whole study from week 0 to week 20

Collaborators and Investigators

• Sponsor: The Third Xiangya Hospital of Central South University
• Investigators: Study Chair: Hao Zhang, Doctor, The Third Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2016
• Primary Completion (Actual): July 30, 2018
• Study Completion (Actual): December 30, 2018

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: May 7, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): October 10, 2019
• Last Update Submitted That Met QC Criteria: October 9, 2019
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Alfacalcidol; Type 2 diabetic nephropathy
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Irbesartan; Alfacalcidol; Hydroxycholecalciferols
• Other Study ID Numbers: 320.6750.16025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO