The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial

This study aims to evaluate the safety and efficacy of Bu Shen Yi Jing (BSYJ) Pill , a type of traditional Chinese medicine, in improving male subfertility and semen parameters.

Study Overview

• Status: Recruiting
• Conditions: Infertility; Male Infertility; Reproductive Issues; Traditional Chinese Medication (TCM)
• Intervention / Treatment: Drug: Placebo Drug; Drug: Bu Shen Yi Jing Pill

Detailed Description

Subfertility is defined as a failure to conceive after 1 year of regular unprotected intercourse. Impaired fertility affects 10 to 15% of couples and male factor is the cause of subfertility in 25 to 40% of couples. With increasing paternal age, semen volume, sperm motility and the percentage of sperm with normal morphology decreases. The majority of men who present with subfertility have either abnormal sperm density, motility or morphology, or a combination of the above, and treatment for this condition is varied and empirical.

There is a paucity of studies and randomized controlled trials to guide treatment of male factor subfertility. Various antioxidant formulations and multivitamins have been used empirically but have not been shown consistently to improve sperm counts and viability. When treatment fails, assisted reproduction will be the last resort. All assisted reproduction treatments are associated with medical, financial and emotional burden. Given the lack of proven treatment options in Western Medicine, Traditional Chinese Medicine (TCM) may provide a viable complementary treatment option. One such option is the Bu Shen Yi Jing (BSYJ) pill.

A clinical observational study conducted by the team in Singapore Thong Chai Medical on subfertile male patients with poor sperm quality and a body constitution of Kidney Deficiency showed that 2 courses of BSYJ pill over a 6 months' duration resulted in successful conception of 33% of azoospermic male patients (n = 60). In a subgroup of patients where serial sperm analysis was available (n=10), the percentage of sperm with grade A motility increased from a median of 22.6 ± 2.4% pre-treatment to 35.1 ± 3.2% post treatment (p < 0.05); and the hyaluronic binding assay improved from 33.2 ± 2.4% to 72 ± 4.6% (p < 0.05). This suggests that BSYJ pills possibly works on improving the motility of the sperms in patients having the Kidney deficiency body constitution.

As such, this study aims to validate these hypotheses and anecdotal evidence by conducting a safety and efficacy study of the BSYJ pill on a prospective cohort.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tat Xin Ee, MD; Phone Number: 97717807; Email: ee.tat.xin@singhealth.com.sg
• Study Contact Backup: Name: Chee Wai Ku, MD; Phone Number: 98365742; Email: gmskcw@nus.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore, 229899
    • Recruiting
    • KK Women's and Children's Hospital
    • Contact: Tat Xin Ee, MD; Phone Number: 97717807; Email: ee.tat.xin@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 49 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Duration of subfertility (both primary and secondary) ≥ 1 year;

• Any or combination of the three abnormal semen parameters, defined according to the 2010 WHO criteria, including

  • Oligozoospermia, with sperm concentration less than 15 x 10^6,
  • Teratozoospermia, with normal sperm morphology less than 4%, and
  • Asthenozoospermia, with total sperm motility less than 40%, or progressive sperm motility less than 32%.
• Diagnosed with TCM syndrome of Kidney Deficiency Based on a prominent TCM diagnosis textbook known as TCM Diagnostics, the main symptoms patients need to fulfil for Kidney Deficiency are either nocturnal polyuria or lower back pain. In addition, patients need to fulfil any 1 of the secondary symptoms, including fatigue; dizziness; tinnitus or deafness; memory loss; excessive urination; low libido; wet dreams; premature ejaculation; presence of feverish palms and soles or night sweats; dry mouth or throat; cold intolerance or preference for warmth; poor sleep quality. Presence of both 1 main symptom and 1 secondary symptom allows for the diagnosis of the Kidney Deficiency syndrome.

Patients who meet all three criteria mentioned above will be included in the study.

Exclusion Criteria:

• Azoospermia and severe oligoasthenoteratozoospermia;
• Aspermia;
• Varicocele;
• Recent urogenital infections;
• Y chromosome deletions;
• Abnormal karyotypes
• History of chemotherapy and / or radiotherapy;
• Patients on fertility supplements or supplements marketed to improve fertility;
• Patients with uncontrolled diabetes or/and hypertension; with uncontrolled chronic medical conditions
• Patients currently already on BSYJ pills treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Patients in this arm will be given a placebo pill that resembles the actual Bu Shen Yi Jing Pill.	Drug: Placebo Drug; Placebo contains the ingredients: grounded black rice and permitted colouring. The ingredients are encapsulated within a gelatine capsule. Dosage of the study drug is as follows: 3 pills each time, for 3 times a day, taken for 6 days every week for 1 year; Other Names: Control drug
ACTIVE_COMPARATOR: Bu Shen Yi Jing Pill; Patients in this arm will be given the BSYJ Pill.	Drug: Bu Shen Yi Jing Pill; Bu Shen Yi Jing Pill contained Radix Pseudostellaria, Fructus Lycii, Radix Et Rhizoma Salviae, Rhizoma Dioscorea, Semen Plantaginis, Semen Cuscuta, Patriniae Herba, Herba Epimedii, Radix Ophiopogonis, Fructus Rubi, Fructus Corni, Bupleurum roots, Fructus Schisandrae Chinensis, Radix Et Rhizoma Glycyrrhizae. Dosage of the study drug is as follows: 3 pills each time, for 3 times a day, taken for 6 days every week for 1 year; Other Names: BSYJ Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the change in sperm volume from baseline after treatment with BSYJ pill	From sperm samples analyses	1 year
To determine the change in sperm morphology from baseline after treatment with BSYJ pill	From sperm samples analyses	1 year
To determine the change in sperm motility from the baseline after treatment with BSYJ pill	From sperm samples analyses	1 year
To determine the change in sperm concentration from the baseline after treatment with BSYJ pill	From sperm samples analyses	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the clinical pregnancy rate and successful delivery rate after BSYJ pill	Defined by the number of pregnancies and subsequent actual births after commencement of BSYJ pill	2 year
To study the safety and determine the changes in blood profile after treatment with BSYJ pill	Defined by changes in participant's full blood count, renal panel, liver function test and hormone profile.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the common side effects of the BSYJ pill	Participant reported symptoms of excessive heat syndrome such as ulcers and mouth dryness.	1 year
To assess the common gastrointestinal side effects of the BSYJ pill	Participant reported symptoms of gastrointestinal symptoms such as indigestion and appetite reduction.	1 year
To evaluate safety profile of BSYJ pill	Participants will be assessed frequently to pick up any side effects noted after commencement of BSYJ pill	Up to 1 year after recruitment
Change from baseline severity based on TCM symptom scoring questionnaire	As BSYJ pills target the TCM syndrome of Kidney Qi deficiency, symptoms related to Kidney Qi deficiency syndrome, which includes frequent urination and back pain, fatigue and dizziness, may be improved through this research.	1 year
Number of participants with improvement in TCM syndrome of Kidney Qi deficiency from baseline according to the TCM symptom scoring questionnaire Stagnation	As BSYJ pills target the TCM syndrome of Kidney Qi deficiency, symptoms related to Kidney Qi deficiency syndrome, which includes frequent urination and back pain, fatigue and dizziness, may be improved through this research.	1 year
Patient's basic demographics	Defined by age, ethnicity, marital status	1 year
Patient's partner's basic demographics	Defined by age, ethnicity, marital status	1 year
Patients's anthropometry	Defined by height, weight and body mass index based on weight (kg) /height (m)2	1 year
Number of participants who smoke	Self-reported	1 year
Number of participants who take alcohol regularly	Self-reported based on the amount and frequency of alcohol intake	1 year
Number of participants who have dietary restrictions	Self-reported	1 year
Number of participants with occupational exposures to chemicals	Self-reported	1 year
Number of participants with exposure to hot baths or jacuzzi	Self-reported	1 year
Number of participants who uses recreational drugs	Self-reported	1 year
Number of participants who exercise regularly	Self-reported	1 year
Number of patients with significant medical history	Self-reported details of medical history	1 year
Number of patients with significant surgical history	Self-reported details of surgical history	1 year
Number of patients on regular medications	Self-reported details of types of regular medications	1 year
Number of patients with drug allergies	Self-reported details of drug allergies	1 year
Number of patients who take supplements	Self-reported details of the type of supplements taken	1 year
Number of patients who take steroids	Self-reported	1 year
Number of patients with previous history of sexually transmitted disease	Self-reported details of sexually transmitted disease	1 year
Number of patients with previous history of genital trauma	Self-reported details of genital trauma	Since birth
Patient's fertility history	Determined by the number of years of attempts at conception, sexual intercourse frequency, number of paternity (including current and/or previous partners), previous fertility treatments and medications	1 year
Patient's partner's fertility history	Determined by the number of years of attempts at conception, sexual intercourse frequency, number of maternity (including current and/or previous partners), previous fertility treatments and medications, and menstrual history	1 year

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Investigators: Principal Investigator: Tat Xin Ee, MD, KK Women's and Children's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 7, 2022
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2024

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: March 13, 2022
• First Posted (ACTUAL): March 22, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Infertility; Sperm; Traditional Medicine
• Additional Relevant MeSH Terms: Infertility; Infertility, Male
• Other Study ID Numbers: 2020/2019

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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