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

Sponsor

Zensun Sci. & Tech. Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04859621

Collaborator

(none)

150

Enrollment

Locations

Arms

26.7

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Recurrent Urinary Tract Infection	Drug: Vitamin D3 4000 IU Drug: Vitamin D3 2000 IU Drug: Placebo Other: standard antibiotic therapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A multicenter, randomized, double-blind, placebo-controlled trialA multicenter, randomized, double-blind, placebo-controlled trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

To ensure that the randomized drug treatment period is double-blind, the study drug and placebo control have the same appearance, smell, and taste. Furthermore, the package and label are also adjusted correspondingly to ensure blindness.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 8, 2021

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Jul 30, 2023

Arms and Interventions

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	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 Other: standard antibiotic therapy standard antibiotic therapy
Placebo Comparator: Placebo Placebo Oral Tablet plus standard antibiotic therapy	Drug: 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

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

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

Other: standard antibiotic therapy

standard antibiotic therapy

Placebo Comparator: Placebo

Placebo Oral Tablet plus standard antibiotic therapy

Drug: 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

Outcome Measures

Primary Outcome Measures

UTI recurrent incidence in 48 weeks [48 weeks]
UTI episodes during 48-week treatment for each subject

Secondary Outcome Measures

Recurrence rate of UTI in 48 weeks [48 weeks]
Comparing the recurrence rate of UTI between different treatment groups
UTI-free duration in 48 weeks [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.
Cumulative relapse-free ratio [48 weeks]
Ratio of the cumulative duration of UTI-free period to treatment duration

Other Outcome Measures

Antibiotic treatment during the recurrence of UTI [48 weeks]
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.
Symptom score of each episode of recurrent lower urinary tract infection [48 weeks]
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.)
Urinary culture bacterial count [48 weeks]
Urinary culture bacterial count at each recurrence of UTI
Blood and urine levels of antimicrobial peptides [48 weeks]
Blood and urine levels of antimicrobial peptides at planned and additional visits

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female aged 18 to 75 years, including 18 and 75 years;
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;
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;
Signed written informed consent;
Be able to follow the research protocol.

Exclusion Criteria:

Complicated with cardio-cerebrovascular and hematopoietic system and other serious primary diseases;
Poor glycemic control (HbA1c >7.5%) with diabetes;
Patients with genital tract malformation or acute genital tract infection and genital tract tumor;
Patients with urinary system tuberculosis and acute pyelonephritis;
Patients with cysto-ureteral reflux or urethral reflux;
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;
Glomerular filtration rate (MDRD formula).20 mL/min/1.73m2, dialysis or kidney transplantation patients;
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);
Patients with vitamin D3 contraindications, such as hypercalcemia, hypervitaminism, hyperphosphatemia with renal rickets, etc.;
Patients with diseases that affect the absorption of vitamin D3 in the small intestine, such as Crohn's disease;
receiving immunosuppressive agents or GT;10 mg/d glucocorticoids;
had received any other investigational drug therapy or participated in another interventional clinical trial within 30 days prior to screening;
Have a history of alcohol or drug abuse or suffer from mental illness;
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;
Circumstances in which subjects are judged by the investigator to be unsuitable for inclusion.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Xi 'an Jiaotong University	Xi'an	Shaanxi	China
2	Shanghai Ruijin Hospital	Shanghai	Shanghai	China	200025
3	Shanghai Oriental Hospital	Shanghai	Shanghai	China
4	The Fifth People's Hospital, Shanghai	Shanghai	Shanghai	China
5	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine，Chongming Branch	Shanghai	Shanghai	China
6	Sichuan Provincial People's Hospital	Chengdu	Sichuan	China