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| Name | Class |
|---|---|
| Fundacio Clinic Barcelona | OTHER |
| Fertypharm | INDUSTRY |
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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® 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 the present clinical trial, such positive effects will be tested again in a higher number of patients, and additional parameters will be included in order to gain insights into the sperm physiological changes that underpin the improvement in semen quality
IInfertility 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 (Culture Collection of Fitoplancton Marino 03), 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 will be 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 our study is to demonstrate the usefulness and safety of TetraSOD® treatment in the improvement of sperm quality including sperm DNA fragmentation. As we 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 our study we are going to also assess the correlation between sperm DNA fragmentation and sORP (static oxidation reduction potential) degree by the use of "MiOXSYS". Therefore, the availability of a simple and cheap instantaneous response time diagnostic test seems promising for the reproductive clinics. It allows us to advance in the diagnosis of male fertility potential and in the identification of those patients susceptible to antioxidant treatment in order to improve their reproductive results, increasing the chances of pregnancy both spontaneously or after assisted reproductive treatment
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | Placebo Comparator | Group supplemented with a daily dose of placebo |
|
| Experimental group | Experimental | Group supplemented with a daily dose of TetraSOD® |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Marine microalgae Tetraselmis chuii with high Superoxide Dismutase (SOD) activity | Dietary Supplement | Participants in the Experimental group will receive a daily dose of 250 mg of TetraSOD® in a capsule during 90 days. After treatment, the group will stop consumption of TetraSOD® and a wash-out period of three months will start |
| Measure | Description | Time Frame |
|---|---|---|
| Sperm Progressive Motility | Sperm progressive motility (in percentage) will be assessed according to the method described in the WHO (World Health Organization) laboratory manual for the examination and processing of human semen, 5th ed. Geneva: World Health Organization (2010) | 90 days |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| DNA Integrity | DNA integrity/fragmentation was evaluated using the COMET assay. Approximately 10,000 sperm from cryopreserved samples were embedded in 1% low-melting-point agarose gel and subjected to lysis. Slides were immersed in either neutral or alkaline electrophoresis buffer for 30 min, followed by electrophoresis at 22 V for 10-15 min, maintaining current below 280 mA to prevent overheating. DNA was then stained with SYBR™ Gold (Invitrogen™, ThermoFisher scientific©, USA) and visualized by fluorescence microscopy. DNA fragments migrated further than intact chromatin, forming a characteristic comet tail. The percentage of fragmented sperm was quantified by analyzing 60-120 cells per sample. |
| Measure | Description | Time Frame |
|---|---|---|
| MiOXSYS System as a Diagnostic Test of Abnormal Seminal Parameters and DNA Fragmentation | In addition to seminal parameters and DNA fragmentation, sORP (static oxidation reduction potential) was also assessed using the MiOXSYS system. The MiOXSYS® galvanostatic system (Caerus Biotechnologies, Switzerland) was used to measure the balance between total oxidant and reductant activity in seminal plasma. For each measurement, 30 μl of fresh ejaculate was deposited on a single-use sample holder chip. The seminal sORP was then displayed in mV on the device screen and subsequently normalized to sperm concentration (sORP/C). Two different cohorts were defined in each experimental group, those presenting a pathological sORP/C (>1.34 mV/million sperm/mL), and those presenting a non-pathological sORP/C (<1.34 mV (millivolt)/million sperm/mL). Seminal parameters and DNA fragmentation wera analyzed in each cohort in each experimental group. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Juan M Corral, Doctor | Hospital Clinic (Barcelona, Spain) | Principal Investigator |
| Meritxell Jodar, Doctor | Hospital Clinic (Barcelona, Spain) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Clinic | Barcelona | 08036 | Spain | |||
| Hospital Clinic |
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Group | Group supplemented with a daily dose of placebo Sham: Participants in the Control group will receive a daily dose of placebo in a capsule during 90 days. After treatment, the group will stop consumption of placebo and a wash-out period of three months will start |
| FG001 | Experimental Group | Group supplemented with a daily dose of TetraSOD® Marine microalgae Tetraselmis chuii with high Superoxide Dismutase (SOD) activity: Participants in the Experimental group will receive a daily dose of 250 mg of TetraSOD® in a capsule during 90 days. After treatment, the group will stop consumption of TetraSOD® and a wash-out period of three months will start |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Visit 1 (3 Months of Supplementation) |
| |||||||||||||
| Visit 2 (3 Months of Wash-out) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Control Group | Group supplemented with a daily dose of placebo Sham: Participants in the Control group will receive a daily dose of placebo in a capsule during 90 days. After treatment, the group will stop consumption of placebo and a wash-out period of three months will start |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Sperm Progressive Motility | Sperm progressive motility (in percentage) will be assessed according to the method described in the WHO (World Health Organization) laboratory manual for the examination and processing of human semen, 5th ed. Geneva: World Health Organization (2010) | Posted | Mean | Standard Deviation | percentage | 90 days |
|
3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control Group | Group supplemented with a daily dose of placebo Sham: Participants in the Control group will receive a daily dose of placebo in a capsule during 90 days. After treatment, the group will stop consumption of placebo and a wash-out period of three months will start |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Protruding in testes | Reproductive system and breast disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Meritxell Jodar | Molecular Biology of Reproduction and Development Research Group, Fundació Recerca Clínic Barcelona - IDIBAPS. Genetics Unit, Department of Biomedicine, Universitat de Barcelona (UB), Barcelona, Spain | +34 93 227 55 10 | mjodar@clinic.cat |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 2, 2020 | Feb 9, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007248 | Infertility, Male |
| D007246 | Infertility |
| ID | Term |
|---|---|
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D013482 | Superoxide Dismutase |
| D015444 | Exercise |
| C005703 | salicylhydroxamic acid |
| ID | Term |
|---|---|
| D010088 | Oxidoreductases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D009043 | Motor Activity |
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|
| Sham | Dietary Supplement | Participants in the Control group will receive a daily dose of placebo in a capsule during 90 days. After treatment, the group will stop consumption of placebo and a wash-out period of three months will start |
|
| 90 days |
| Adverse Effects | Any kind of adverse event attributable to TetraSOD® will be recorded during the duration of the trial | 90 days |
| 90 days |
| Barcelona |
| Spain |
| NOT COMPLETED |
|
| Experimental Group |
Group supplemented with a daily dose of TetraSOD® Marine microalgae Tetraselmis chuii with high Superoxide Dismutase (SOD) activity: Participants in the Experimental group will receive a daily dose of 250 mg of TetraSOD® in a capsule during 90 days. After treatment, the group will stop consumption of TetraSOD® and a wash-out period of three months will start |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Number | participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | Kg/m^2 |
|
|
|
| Primary | 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) | Posted | Mean | Standard Deviation | Million sperm/ml | 90 days |
|
|
|
| Secondary | DNA Integrity | DNA integrity/fragmentation was evaluated using the COMET assay. Approximately 10,000 sperm from cryopreserved samples were embedded in 1% low-melting-point agarose gel and subjected to lysis. Slides were immersed in either neutral or alkaline electrophoresis buffer for 30 min, followed by electrophoresis at 22 V for 10-15 min, maintaining current below 280 mA to prevent overheating. DNA was then stained with SYBR™ Gold (Invitrogen™, ThermoFisher scientific©, USA) and visualized by fluorescence microscopy. DNA fragments migrated further than intact chromatin, forming a characteristic comet tail. The percentage of fragmented sperm was quantified by analyzing 60-120 cells per sample. | Posted | Mean | Standard Deviation | percentage of sperm with fragmented DNA | 90 days |
|
|
|
| Secondary | Adverse Effects | Any kind of adverse event attributable to TetraSOD® will be recorded during the duration of the trial | Posted | Number | Number of participants | 90 days |
|
|
|
| Other Pre-specified | MiOXSYS System as a Diagnostic Test of Abnormal Seminal Parameters and DNA Fragmentation | In addition to seminal parameters and DNA fragmentation, sORP (static oxidation reduction potential) was also assessed using the MiOXSYS system. The MiOXSYS® galvanostatic system (Caerus Biotechnologies, Switzerland) was used to measure the balance between total oxidant and reductant activity in seminal plasma. For each measurement, 30 μl of fresh ejaculate was deposited on a single-use sample holder chip. The seminal sORP was then displayed in mV on the device screen and subsequently normalized to sperm concentration (sORP/C). Two different cohorts were defined in each experimental group, those presenting a pathological sORP/C (>1.34 mV/million sperm/mL), and those presenting a non-pathological sORP/C (<1.34 mV (millivolt)/million sperm/mL). Seminal parameters and DNA fragmentation wera analyzed in each cohort in each experimental group. | Posted | Mean | Standard Deviation | mV/10^6 sperm/mL | 90 days |
|
|
|
| 0 |
| 31 |
| 2 |
| 31 |
| 0 |
| 31 |
| EG001 | Experimental Group | Group supplemented with a daily dose of TetraSOD® Marine microalgae Tetraselmis chuii with high Superoxide Dismutase (SOD) activity: Participants in the Experimental group will receive a daily dose of 250 mg of TetraSOD® in a capsule during 90 days. After treatment, the group will stop consumption of TetraSOD® and a wash-out period of three months will start | 0 | 31 | 0 | 31 | 0 | 31 |
| Epididymitis | Reproductive system and breast disorders | Systematic Assessment |
|
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| D009068 |
| Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |