Clinical trial NCT04859621: Phase II Clinical Trial of Vitamin D3 for Reducing Recurrence of Recurrent Lower Urinary Tract Infections
Official title: Phase II Clinical Trial of Vitamin D3 for Reducing Recurrence of Recurrent Lower Urinary Tract Infections: a Multicenter, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Urinary Tract Infection
Keywords: Vitamin D3
Recurrent lower urinary tract infection
Lead sponsor: Zensun Sci. & Tech. Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-26
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multicenter, randomized, double-blind, placebo-controlled trial
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: UTI recurrent incidence in 48 weeks
timeFrame: 48 weeks
Secondary outcomes:
measure: Recurrence rate of UTI in 48 weeks
timeFrame: 48 weeks
measure: UTI-free duration in 48 weeks
timeFrame: 48 weeks
measure: Cumulative relapse-free ratio
timeFrame: 48 weeks
Other outcomes:
measure: Antibiotic treatment during the recurrence of UTI
timeFrame: 48 weeks
measure: Symptom score of each episode of recurrent lower urinary tract infection
timeFrame: 48 weeks
measure: Urinary culture bacterial count
timeFrame: 48 weeks
measure: Blood and urine levels of antimicrobial peptides
timeFrame: 48 weeks
Locations:
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Shanghai
country: China
facility: Shanghai Oriental Hospital
state: Shanghai
city: Shanghai
country: China
facility: The Fifth People's Hospital, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine，Chongming Branch
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
affiliation: Zhejiang Provincial People's Hospital
name: Xian He, MD
role: PRINCIPAL_INVESTIGATOR
References: