Phase II Clinical Trial of Vitamin D3 for Reducing Recurrence of Recurrent Lower Urinary Tract Infections

Phase II Clinical Trial of Vitamin D3 for Reducing Recurrence of Recurrent Lower Urinary Tract Infections: a Multicenter, Randomized, Placebo-controlled Trial

The aim of this study was to initially evaluate the optimal dose, efficacy, and safety of vitamin D3 for reducing recurrence of recurrent urinary tract infections (rUTIs).

Study Overview

• Status: Recruiting
• Conditions: Recurrent Urinary Tract Infection
• Intervention / Treatment: Drug: Vitamin D3 4000 IU; Other: standard antibiotic therapy; Drug: Vitamin D3 2000 IU; Drug: Placebo

Detailed Description

Urinary tract infection (UTI) is a multiple disease that ranks second only to respiratory infections in infectious diseases and is one of the most common infectious diseases among adults. After the first urinary tract infection, the probability of recurrence within half a year and within one year was as high as 24% and 70%, respectively. Urinary tract infection itself has the characteristics of easy recurrence, which is closely related to the abuse of antibiotics, the generation of bacterial resistance, and the decline of local immune function of mucosa.

In the urinary tract, the antibacterial peptide Cathelicidin is mainly located in the proximal tubules of the kidney and the epithelial cells of the renal pelvis and ureter. LL37 is the only antibacterial peptide present in the human body of the Cathelicidin family, which can be regarded as a natural antibiotic produced by the body. Antibacterial peptides have a broad-spectrum antibacterial effect and can exert antibacterial effects against both Gram-positive and Gram-negative bacteria. Vitamin D intake increases the activity of endogenous antimicrobial peptides. Preclinical cell test of Zensun Sci. & Tech. Co., Ltd. confirmed the induction of LL37 in urethral epithelial cells by vitamin D and its broad-spectrum antibacterial effect. Animal experiments also showed the therapeutic effect of LL37 on UTI.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Debing Jiang; Phone Number: 86-21-50802627; Email: dbjiang@zensun.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Recruiting
      • The First Affiliated Hospital of Xi 'an Jiaotong University
      • Contact: Aiping Yin; Phone Number: 18991232130; Email: aipingy@126.com
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Oriental Hospital
      • Contact: Na Liu; Phone Number: 18217768587; Email: naliubrown@163.com
    • Shanghai, Shanghai, China
      • Recruiting
      • The Fifth People's Hospital, Shanghai
      • Contact: Jianying Niu; Phone Number: 18918168518; Email: njyphd2008@163.com
    • Shanghai, Shanghai, China
      • Recruiting
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine，Chongming Branch
      • Contact: Chun Zhu; Phone Number: 13611951773; Email: zhuchun26@sina.cn
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • Sichuan Provincial People's Hospital
      • Contact: Li Wang; Phone Number: 13708016939; Email: scwangli62@163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 200025
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Xian He, MD; Phone Number: 57185239988; Email: Hx.hzsy@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged 18 to 75 years, including 18 and 75 years;
2. at least 3 episodes of lower urinary tract infection in the last 12 months or at least 2 episodes of lower urinary tract infection in the last 6 months;
3. The symptoms of the latest recurrence of lower urinary tract infection have disappeared after treatment, and the treatment dosage of antibiotics has been stopped, and at least one of the following two conditions has been met:A) The middle urinary bacterial culture is less than 10^5 CFU/mL (accept the examination results after the last improvement);B) Urine white blood cell count is less than 5 /HP, and if it can be measured in routine urine examination, it should be less than 25 /μL;
4. Signed written informed consent;
5. Be able to follow the research protocol.

Exclusion Criteria:

1. Complicated with cardio-cerebrovascular and hematopoietic system and other serious primary diseases;
2. Poor glycemic control (HbA1c >7.5%) with diabetes;
3. Patients with genital tract malformation or acute genital tract infection and genital tract tumor;
4. Patients with urinary system tuberculosis and acute pyelonephritis;
5. Patients with cysto-ureteral reflux or urethral reflux;
6. Patients with polycystic kidney disease, neurogenic bladder, indwelling urethral catheterization, urinary tract stones, tumors or fibrous degeneration, etc., determined by the investigator as urinary tract obstruction;
7. Glomerular filtration rate (MDRD formula).20 mL/min/1.73m2, dialysis or kidney transplantation patients;
8. Chronic liver disease may have potential influence on liver function (bilirubin >;1.5 times upper limit of normal value, aspartate aminotransferase or alanine aminotransferase >2 times the upper limit of normal);
9. Patients with vitamin D3 contraindications, such as hypercalcemia, hypervitaminism, hyperphosphatemia with renal rickets, etc.;
10. Patients with diseases that affect the absorption of vitamin D3 in the small intestine, such as Crohn's disease;
11. receiving immunosuppressive agents or GT;10 mg/d glucocorticoids;
12. had received any other investigational drug therapy or participated in another interventional clinical trial within 30 days prior to screening;
13. Have a history of alcohol or drug abuse or suffer from mental illness;
14. Women of child-bearing age who have planned to become pregnant within 2 years (women of child-bearing age are defined as all women with physical ability to become pregnant), or women who are pregnant or lactating;
15. Circumstances in which subjects are judged by the investigator to be unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D3 4000 IU; 4000IU Vitamin D3 Oral Tablet plus standard antibiotic therapy	Drug: Vitamin D3 4000 IU; Oral administration, 2 tablet per time, qd, oral administration with the first meal, continuous use for 48 weeks; Other: standard antibiotic therapy; standard antibiotic therapy
Experimental: Vitamin D3 2000 IU; 2000IU Vitamin D3 Oral Tablet plus standard antibiotic therapy	Other: standard antibiotic therapy; standard antibiotic therapy; Drug: Vitamin D3 2000 IU; Oral administration, 1 tablet of each per time, qd, oral administration with the first meal, continuous use for 48 weeks
Placebo Comparator: Placebo; Placebo Oral Tablet plus standard antibiotic therapy	Other: standard antibiotic therapy; standard antibiotic therapy; Drug: Placebo; Oral administration, 2 tablet per time, qd, oral administration with the first meal, continuous use for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UTI recurrent incidence in 48 weeks	UTI episodes during 48-week treatment for each subject	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate of UTI in 48 weeks	Comparing the recurrence rate of UTI between different treatment groups	48 weeks
UTI-free duration in 48 weeks	Comparing the number of days from the beginning of the study to the first recurrence of UTI, and the number of days from each recurrence to the next recurrence between different treatment groups.	48 weeks
Cumulative relapse-free ratio	Ratio of the cumulative duration of UTI-free period to treatment duration	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibiotic treatment during the recurrence of UTI	Subjects will be given antibiotics during the recurrence of UTI, type/name and the duration of antibiotic treatment will be compared between different treatment groups.	48 weeks
Symptom score of each episode of recurrent lower urinary tract infection	Symptom score of each episode of UTI will be evaluated using an overall impression scale with 7 severity levels ( "a" means the best outcome and "g" as the worst outcome.)	48 weeks
Urinary culture bacterial count	Urinary culture bacterial count at each recurrence of UTI	48 weeks
Blood and urine levels of antimicrobial peptides	Blood and urine levels of antimicrobial peptides at planned and additional visits	48 weeks

Collaborators and Investigators

• Sponsor: Zensun Sci. & Tech. Co., Ltd.
• Investigators: Principal Investigator: Xian He, MD, Zhejiang Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2021
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Vitamin D3; Recurrent lower urinary tract infection
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Recurrence; Urinary Tract Infections; Physiological Effects of Drugs; Anti-Infective Agents; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Anti-Bacterial Agents; Vitamins; Ergocalciferols
• Other Study ID Numbers: ZS-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No