Clinical trial NCT05290558: The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
Official title: The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Male Infertility
Infertility
Traditional Chinese Medication (TCM)
Reproductive Issues
Keywords: Infertility
Sperm
Traditional Medicine
Lead sponsor: KK Women's and Children's Hospital
Sponsor class: OTHER_GOV
First posted: 2022-03-22
Enrollment: 59
Sex: MALE
Minimum age (years): 21
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a double-blinded randomised control trial. Participants will be randomised using block randomization by a pre-determined randomisation schedule generated by a biostatistician in block size of 4. Enrolment and assignment of intervention will be carried out by an investigator. The investigators will perform block randomization of the subjects in blocks of 4 in the ratio of 1:1 such that 2 will be assigned to treatment and 2 will be assigned to placebo.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the change in sperm volume from baseline after treatment with BSYJ pill
timeFrame: 1 year
measure: To determine the change in sperm morphology from baseline after treatment with BSYJ pill
timeFrame: 1 year
measure: To determine the change in sperm motility from the baseline after treatment with BSYJ pill
timeFrame: 1 year
measure: To determine the change in sperm concentration from the baseline after treatment with BSYJ pill
timeFrame: 1 year
Secondary outcomes:
measure: To determine the clinical pregnancy rate and successful delivery rate after BSYJ pill
timeFrame: 2 year
measure: To study the safety and determine the changes in blood profile after treatment with BSYJ pill
timeFrame: 1 year
Other outcomes:
measure: To assess the common side effects of the BSYJ pill
timeFrame: 1 year
measure: To assess the common gastrointestinal side effects of the BSYJ pill
timeFrame: 1 year
measure: To evaluate safety profile of BSYJ pill
timeFrame: Up to 1 year after recruitment
measure: Change from baseline severity based on TCM symptom scoring questionnaire
timeFrame: 1 year
measure: Number of participants with improvement in TCM syndrome of Kidney Qi deficiency from baseline according to the TCM symptom scoring questionnaire Stagnation
timeFrame: 1 year
measure: Patient's basic demographics
timeFrame: 1 year
measure: Patient's partner's basic demographics
timeFrame: 1 year
measure: Patients's anthropometry
timeFrame: 1 year
measure: Number of participants who smoke
timeFrame: 1 year
measure: Number of participants who take alcohol regularly
timeFrame: 1 year
measure: Number of participants who have dietary restrictions
timeFrame: 1 year
measure: Number of participants with occupational exposures to chemicals
timeFrame: 1 year
measure: Number of participants with exposure to hot baths or jacuzzi
timeFrame: 1 year
measure: Number of participants who uses recreational drugs
timeFrame: 1 year
measure: Number of participants who exercise regularly
timeFrame: 1 year
measure: Number of patients with significant medical history
timeFrame: 1 year
measure: Number of patients with significant surgical history
timeFrame: 1 year
measure: Number of patients on regular medications
timeFrame: 1 year
measure: Number of patients with drug allergies
timeFrame: 1 year
measure: Number of patients who take supplements
timeFrame: 1 year
measure: Number of patients who take steroids
timeFrame: 1 year
measure: Number of patients with previous history of sexually transmitted disease
timeFrame: 1 year
measure: Number of patients with previous history of genital trauma
timeFrame: Since birth
measure: Patient's fertility history
timeFrame: 1 year
measure: Patient's partner's fertility history
timeFrame: 1 year
Locations:
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
Study officials:
affiliation: KK Women's and Children's Hospital
name: Tat Xin Ee, MD
role: PRINCIPAL_INVESTIGATOR
References: