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

Recurrent Urinary Tract Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04859621
• Other study ID #: ZS-05
• Status: Recruiting
• Phase: Phase 2
• Start date: May 8, 2021
• Est. completion date: July 30, 2025

Study information

• Verified date: January 2024
• Source: Zensun Sci. & Tech. Co., Ltd.
• Contact: Debing Jiang
• Phone: 86-21-50802627
• Email: dbjiang[@]zensun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: July 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Recurrence
• Recurrent Urinary Tract Infection
• Urinary Tract Infections

Intervention

Drug:
• Vitamin D3 4000 IU
Oral administration, 2 tablet per time, qd, oral administration with the first meal, continuous use for 48 weeks
• 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
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

Locations

Country	Name	City	State
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Shanghai Oriental Hospital	Shanghai	Shanghai
China	The Fifth People's Hospital, Shanghai	Shanghai	Shanghai
China	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Chongming Branch	Shanghai	Shanghai
China	The First Affiliated Hospital of Xi 'an Jiaotong University	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Zensun Sci. & Tech. Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Urinary culture bacterial count	Urinary culture bacterial count at each recurrence of UTI	48 weeks
Other	Blood and urine levels of antimicrobial peptides	Blood and urine levels of antimicrobial peptides at planned and additional visits	48 weeks
Primary	UTI recurrent incidence in 48 weeks	UTI episodes during 48-week treatment for each subject	48 weeks
Secondary	Recurrence rate of UTI in 48 weeks	Comparing the recurrence rate of UTI between different treatment groups	48 weeks
Secondary	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
Secondary	Cumulative relapse-free ratio	Ratio of the cumulative duration of UTI-free period to treatment duration	48 weeks