Clinical trial NCT04193358: Impact of A Nutritional Supplements' Combination (FERTILIS) on Male Infertility
Official title: Impact of A Nutritional Supplements' Combination (FERTILIS) On Male Infertility: A Monocentric Double Blind Randomized Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infertility, Male
Subfertility, Male
Lead sponsor: Les Laboratoires des Médicaments Stériles
Sponsor class: INDUSTRY
First posted: 2019-12-10
Enrollment: 300
Sex: MALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparative, interventional, prospective, monocentric, double blind, randomized, placebo controlled trial.
Primary purpose: TREATMENT

Brief summary: Infertility is a major health problem affecting up to 15% of couples of reproductive age globally. For several years, it was assumed that most reproductive problems could be attributed to the female partner, but research in recent years has demonstrated that males were solely responsible for 20-30% of infertility cases and contributed to 50% of infertility cases overall. The term ''male infertility'' does not constitute a defined clinical syndrome, but rather a collection of different conditions exhibiting a variety of etiologies.

It is far increasingly known that reactive oxygen species (ROS) are of significant pathophysiological importance in the etiology of male infertility. ROS are highly reactive oxidizing agents belonging to the class of free radicals containing one or more unpaired electrons, which are continuously being generated through metabolic and pathophysiologic processes. It has been suggested that oxidants interfere with normal sperm function via membrane lipid peroxidation and fragmentation of nucleic acids, which result in sperm dysfunction. Due to the sperm cell membrane abundance of polyunsaturated fatty acids (PUFAs) and the capacity of sperm to generate ROS, human spermatozoa are highly susceptible to oxidative stress.

Since growing evidence indicates that oxidative stress can be a primary cause of male infertility, non-enzymatic antioxidants play a significant protective role against oxidative damages and lipid peroxidation. In addition, micronutrients and antioxidants are often used with good results in men with idiopathic infertility.

Keeping in view the main protection provided by seminal plasma antioxidants against oxidative damages, a previous study showed that the dietary management with an eight nutritional supplements' combination, similar to this study's product and containing antioxidants, achieved a significant improvement in sperm quality up to a completely normal semen analysis. Also, another study confirmed the hypothesis that the combination of individual nutritional supplements as described in literature showed significantly better results than the sum of the effects of single administration.


Eligibility criteria: Inclusion Criteria:

* Male ≥ 20 years of age
* Attending the Department of Obstetrics and Gynecology of Farhat Hached University Hospital, Sousse, Tunisia, for consultation or semen analysis as part of infertility investigations
* Diagnosis of oligozoospermia (WHO 2010 definition)
* Diagnosis of Asthenozoospermia (WHO 2010 definition)
* Diagnosis of teratozoospermia1 (WHO 2010 definition)
* Diagnosis of idiopathic infertility
* Couple is candidate for Intrauterine Insemination (IUI), In Vitro Fertilization (IVF) and/or Intracytoplasmic Sperm Injection (ICSI).

Exclusion Criteria:

* Inclusion visit (prior to treatment initiation): Patients will be selected during this initial visit if they meet all inclusion and none of the exclusion criteria.
* Randomization visit: around 1-week post inclusion visit: Patients will be given either of study interventions.
* Follow up visit 1-month post treatment initiation: Patients will be given study interventions' refill for 1 month.
* Follow up visit 2-months post treatment initiation: Patients will be given study interventions' refill for another month.
* Follow up visit 3-months post treatment initiation: Patients will undergo laboratory assessment.
* Follow up visits every 3-months post Visit: Patients' female partner will undergo laboratory and clinical assessment.
* End of trial (CLOSING) visit 24-months post treatment initiation: Patients' female partner will undergo laboratory and clinical assessment.

Primary outcomes:
measure: Sperm DNA fragmentation Index (DFI)
timeFrame: 3 months
Secondary outcomes:
measure: Sperm quantity
timeFrame: 3 months
measure: Sperm quality
timeFrame: Up to 3 months
measure: Occurrence of spontaneous pregnancy
timeFrame: Through study completion, an average of 2 years
measure: Occurrence of pregnancy consecutive to Assisted Reproductive Technology (ART)
timeFrame: Through study completion, an average of 2 years
measure: Fertilization rate during in vitro fertilization (IVF)
timeFrame: Up to 3 months
measure: Embryo cleavage rate and embryo quality during intracytoplasmic sperm injection (ICSI)
timeFrame: Up to 3 months
measure: Achievement of clinical pregnancy
timeFrame: Through study completion, an average of 2 years
measure: Achievement of live birth
timeFrame: Through study completion, an average of 2 years
measure: Number of Adverse Events
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Sousse
country: Tunisia
facility: Farhat Hached Hospital
Study officials:
affiliation: Farhat Hached Hospital
name: Mounir Ajina, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Farhat Hached Hospital
name: Latifa Lassoued, Dr.
role: PRINCIPAL_INVESTIGATOR
References: