Study to Verify the Efficacy of a Product Containing 125 mg of TetraSOD® for the Treatment of Male Infertility

A Double-blind Randomized Placebo-controlled Clinical Study to Verify the Efficacy of TetraSOD® in the Improvement of Semen Quality in Patients With iIdiopathic Infertility

TetraSOD® is a unique marine phytoplankton (Tetraselmis chuii) SOD-rich ingredient that is grown under patent-protected technology exclusively designed by the company Fitoplancton Marino, S.L. (Spain). In a previous pilot trial, the ability of TetraSOD® (dose: 250 mg/day) to improve semen characteristics in idiopathic infertile men after three months of treatment was assessed, revealing significant improvements in almost all of the analyzed parameters. In a further clinical trial close to finish (ClinicalTrials.gov Identifier: NCT04864314) using the same dose, such positive results have been tested again in a higher number of patients, and additional parameters have been included in order to gain insights into the sperm physiological changes that underpin the improvement in semen quality. In this new clinical trial, an intermediate dose (125 mg/day) is going to be tested in an attempt to determine a range of TetraSOD® dosage being clinically active for the treatment of male infertility.

Study Overview

• Status: Recruiting
• Conditions: Male Infertility
• Intervention / Treatment: Dietary supplement: Sham; Dietary supplement: Marine microalgae Tetraselmis chuii with high Superoxide Dismutase (SOD) activity

Detailed Description

Infertility is an increasing global public health problem present in about 15-20% of the population of reproductive age, affecting as many as 186 million people worldwide. A male factor is present in approximately 50% of the infertile couples, a large number of them of unknown or idiopathic origin.

Spermatogenesis is a complex biological process that requires a highly regulated genetic and hormonal program in a singular environment created by the interaction with different cell types to orchestrate a successful differentiation process. This process occurs periodically every 72 days during a man's fertile life. It has been demonstrated that semen quality is deteriorating over the time, perhaps as a result of exposition to several environmental factors related with lifestyle: drug use (such us tobacco, alcohol, marijuana, cocaine, opioids and anabolic agents), diet and overweight, disorders of the sleep-wake cycle and working conditions (continuous exposition to heat sources or toxic substances) that could impact both directly and indirectly on the complex process of spermatogenesis.

Currently, the impact of oxidative stress, a cellular state product of an imbalance between the generation of highly unstable molecules known as reactive oxygen species (ROS) and the antioxidant cellular capacity in male fertility is being deeply investigated. High levels of oxidative stress in semen have been associated with both lower sperm concentration, sperm motility and acrosome integrity and higher sperm DNA damage and mitochondrial activity. Recent clinical trials have demonstrated the high prevalence of sperm DNA damage by up to 80% of men diagnosed with idiopathic male infertility. This DNA damage produced during spermatogenesis or sperm maturation process could be the result of an increase of reactive oxygen species (ROS) in male reproductive tract, which are related to different known factors (chronic systemic disease, use of some drugs, radiation or pesticides, febrile processes, old age and environmental factors related to lifestyle: smoking, obesity, alcohol) and other unknown so far.

Antioxidant supplementation has gained relevance within routine practices in patients with reproductive problems. Different studies have shown the beneficial effect of antioxidant consumption against oxidative damage caused by environmental and pathological components, improving sperm characteristics associated with the seminal analysis. There are scientific evidences about the improvement of male fertility and higher rates of live newborn after antioxidant treatment in subfertile men.

TetraSOD® is a unique commercial product comprised of 100% lyophilized biomass of the marine microalgae Tetraselmis chuii strain CCFM03, which is currently marketed for food and nutraceutical applications around the world by the company Fitoplancton Marino, S.L. This microalgae product is characterized by a high content in the antioxidant enzyme superoxide dismutase (SOD), as it is produced using own (patent pending) technology developed by the company. Results of in vitro studies with human cell lines suggest that TetraSOD® stimulates the cellular protective mechanisms against oxidative stress. Moreover, results previously obtained in a pilot study with the highest dose of TetraSOD® (250 mg/day) were promising, since a high statistically significant response was observed in three of the four studied parameters after three months of treatment.

Taking into account these results, a new extended double-blind randomized and placebo-controlled clinical study has been performed to confirm the positive effects of dietary supplementation with 250 mg of TetraSOD® during 3 months (corresponding to the time of a complete spermatogenic cycle) in sperm quality.

The main objective of this new study is to check the usefulness of a lower dose of TetraSOD® (125 mg/day) in the improvement of sperm quality, including sperm DNA fragmentation. As previously mentioned, oxidative stress is one of the main causes of sperm DNA damage. Nowadays, a diagnostic test for the study of the sperm DNA fragmentation exists, but it requires a specific sperm sample processing and the results are obtained in delay-time. In this new trial, correlation between sperm DNA fragmentation and static oxidation reduction potential (sORP) degree by the use of the Male Infertility Oxidative System (MiOXSYS) will be also tested as in the previous one with a higher dose of TetraSOD® (250 mg/day). Classical seminal parameters (semen volume, sperm concentration and number, sperm progressive motility) will be also quantified. In that way, with this new trial it will be possible to determine a range of TetraSOD® dosage being clinically active for the treatment of male infertility.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carlos Infante; Phone Number: +34 956561079; Email: carlos.infante@easyalgae.com
• Study Contact Backup: Name: Carlos Unamunzaga; Phone Number: +34 956561079; Email: cue@easyalgae.com

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic
    • Contact: Juan M Corral; Phone Number: +34 932275545; Email: jmcorral@clinic.cat
    • Contact: Meritxell Jodar; Phone Number: +34 932275510; Email: mjodar@clinic.cat
    • Sub-Investigator: Marta Guimerà
    • Sub-Investigator: Juan M Mayorga-Torres
    • Sub-Investigator: Antonio Alcaraz
    • Sub-Investigator: Dolors Manau
    • Sub-Investigator: Rafael Oliva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 18 to 45
• Male patients with idiopathic infertility classified with asthenozoospermia, oligozoospermia or oligoasthenozoospermia after seminal assessment.
• Not achieving pregnancy after at least one year of intercourse with the same partner without protective measures

Exclusion Criteria:

• Azoospermia (absence of spermatozoa) or severe oligozoospermia (< 5 x 10^6 spermatozoa/ml of ejaculate)
• Testicular torsion or prostatitis
• Urinary retention and infections
• Drug consumption
• Hormone treatments
• Recent surgical interventions
• Diabetes
• Kidney or liver disease
• Leukocytosis
• Antioxidant supplement consumption in the last 3 months
• BMI>30 Kg/m2
• Endocrinopathies, hypo and hyperthyroidism
• Chromosomal anomalies (XX, XYY, XXY)
• Treatments with anticoagulants
• Radiotherapy/Chemotherapy
• Participation in another clinical study prior to inclusion in this study that could affect the objectives of the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control group; Group supplemented with a daily dose of placebo	Dietary supplement: Sham; Participants in the Control group will receive a daily dose of placebo in a capsule during 90 days.
Experimental: Experimental group; Group supplemented with 125 mg/day of TetraSOD®	Dietary supplement: Marine microalgae Tetraselmis chuii with high Superoxide Dismutase (SOD) activity; Participants in the Experimental group will receive a daily dose of 125 mg of TetraSOD® in a capsule during 90 days.; Other Names: TetraSOD®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sperm concentration	Sperm concentration will be determined according to the method described in the WHO laboratory manual for the examination and processing of human semen, 5th ed. Geneva: World Health Organization (2010)	90 days
Sperm oxidative stress	Sperm ROS intracellular will be measured by flow cytometry evaluating the sperm intracellular ROS (superoxide anion, hydroxyl radical, hydrogen peroxide)	90 days
Sperm motility	Sperm motility will be assessed according to the method described in the World Health Organization (WHO) laboratory manual for the examination and processing of human semen, 5th ed. Geneva: World Health Organization (2010)	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA integrity	DNA integrity/fragmentation will be evaluated using the COMET assay	90 days
Adverse effects	Any kind of adverse event attributable to TetraSOD® will be recorded during the duration of the trial	90 days
sORP by MiOXSYS	sORP will be also assessed using the MiOXSYS system	90 days

Collaborators and Investigators

• Sponsor: Fitoplancton Marino, S.L.
• Collaborators: Fundacio Clinic Barcelona; Fertypharm
• Investigators: Principal Investigator: Juan M Corral, Hospital Clinic Barcelona, Spain; Principal Investigator: Meritxell Jodar, Hospital Clinic Barcelona, Spain

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Oxidative stress; TetraSOD®; Idiopathic Male Infertility
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Infertility; Infertility, Male; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Free Radical Scavengers; Superoxide Dismutase
• Other Study ID Numbers: 2022_TSOD_125

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