Efficacy Study of a Food Supplement With Myo-inositol, N-Acetyl-Cystein, Zinc and Vitamins on Sperm DNA Fragmentation

NCT ID: NCT04959864

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-07
• Study Completion Date: 2026-07-31

Brief Summary

In industrialised countries, it is estimated that about 15% of couples who wish to have a child are currently facing infertility problems, of which, in half of the cases, an anomaly in sperm quality or at least a factor of male origin is identified. The evaluation of sperm quality in males is based, for the most part, on the micro and macroscopic examination of various parameters (concentration, motility, physical abnormalities of the spermatozoa, etc.). Nevertheless, an increasing number of scientific studies have shown that the quality of sperm DNA, and in particular its fragmentation rate, is also associated with a lower fertilisation rate. The integrity of sperm DNA may be affected by an imbalance in the Red/Ox balance leading to uncompensated oxidative stress, and could be restored or improved by dietary hygiene measures and the consumption of specific dietary products. The ISITOL clinical study aims to evaluate the efficacy of a dietary supplement specifically formulated to target the various issues associated with male infertility, and in particular to contribute to the improvement of the sperm DNA fragmentation rate. The efficacy of the dietary supplement Isitol® (GYNOV SAS) on sperm DNA fragmentation rate and other secondary parameters is being evaluated through a single-centre, prospective, randomised, double-blind, interventional vs. placebo clinical study being conducted in France at Laboratoire Drouot (21 Rue Drouot - 75009 Paris - France) and led by Dr. Nino-Guy Cassuto. A total of 72 men aged between 20 and 45 years, with sperm DNA fragmentation rate ≥ 30% and with negative semen culture are recruited. The recruited patients were randomized in a 1:1 scheme into 2 groups (Isitol® treated vs placebo treated).

[Results to be reported later]

Detailed Description

Infertility is generally defined as a partner's failure to conceive after at least 12 months off contraception and is steadily increasing worldwide. In industrialised countries, it is estimated that around 15% of couples who wish to have a child are now facing it, and in half of the cases, an abnormality in sperm quality or at least a male factor is identified.

In males, the measurement of male fertility is mainly based on analyses that assess sperm quality macroscopically (spermiogram, spermocytogram) by evaluating the number, morphology, motility, presence of abnormalities, etc. These indicators are still considered to be the preferred indicators for assessing male fertility.

Nevertheless, since the mid-2000s, numerous in vitro and in vivo studies in humans and animals have shown that the integrity of sperm DNA, assessed by measuring the rate of DNA fragmentation and chromatin decondensation in spermatozoa, could be a relevant parameter in the etiology of male infertility. Furthermore, it has been observed that the rate of sperm DNA fragmentation is inversely correlated with pregnancy rate, success rate of assisted reproductive techniques and embryo quality.

The major identified cause of direct damage to DNA molecules and their possible fragmentation, but also to proteins and cell membranes in spermatozoa is oxidative stress. Unreduced Reactive oxygen species produced in the mitochondria-rich midpiece in excess are susceptible to damage the DNA in the sperm head. Several exogenous factors such as exposure to toxins, smoking, alcohol or unbalanced diet are also associated with promoting oxidative stress.

A fragmentation rate higher than 30% is considered high, it is indicative of altered chromatin and especially associated with a low probability of conceiving naturally or through in vitro techniques.

To resolve this problem and improve the process of spermatogenesis and fertilisation, it is relevant to evaluate the effectiveness of a food supplement (Isitol®), manufactured and marketed by the company Gynov SAS (2B Rue Sauteyron - 33000 Bordeaux - France), which provides myo-inositol and a complex with antioxidant properties based on N-acetyl-cysteine, group B vitamins (B2, B3, B6, B9), vitamin E and zinc.

In addition to providing the nutrients that contribute to a better management of the reactive oxygen species, the food supplement provides myo-inositol, which is essential for the functioning of a wide range of cellular functions. This molecule, related to glucose, is produced in the testis, mainly by Sertoli cells, and is excreted into the seminiferous tubules as a gradient. This gradient contributes to sperm maturation by reducing sperm viscosity and increasing sperm motility. Numerous studies evaluating the impact of myo-inositol have shown a significant improvement in sperm parameters (concentration, motility, morphology) and in particular in the rate of sperm DNA fragmentation.

In order to evaluate the efficacy of this dietary supplement, a single-centre, prospective, randomised, double-blind, interventional vs. placebo clinical study was set up in France at Laboratoire Drouot (21 Rue Drouot - 75009 Paris - France) and directed by Dr. Nino-Guy Cassuto. A total of 72 men aged between 20 and 45 years, with sperm DNA fragmentation rate ≥ 30% and with negative semen culture are recruited. The recruited patients were randomised in a 1:1 design into 2 groups (Isitol® treated vs placebo treated).

The primary hypothesis is that after 16 (± 2) weeks of treatment with the dietary supplement, the expected decrease in sperm DNA fragmentation rate will be ≥ 23% compared to the placebo treated group to validate the efficacy hypothesis. The measurement of the sperm DNA fragmentation rate is performed by TUNEL (Terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling) method. The secondary objectives are the evaluation of classical sperm parameters (spermiogram, spermocytogram), sperm morphology score, chromatin decondensation rate, sperm red/ox potential, differential expression of 11 specific genes involved in spermatogenesis and/or at different stages of the fertilisation process (AURKA, CCDC60, CCDC88B, etc.)).

[Results to be reported later]

Conditions

Male Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Isitol® (Food supplement treated group)

36 eligible males between 20 and 45 yo. (included limits) will take 1 sachet of Isitol® per day during 16 (± 2) weeks. The sachet of powder is to dissolve in a glass of water or directly in mouth.

1 sachet of Isitol® (2,1g) contains 1000 mg of myo-inositol, 300 mg of N-acetyl-cysteine, 150 % of the Nutritional Reference Values (NRV) in zinc and 100 % of the NRV: in vitamins B2, B3, B6, B9 and E.

Group Type: EXPERIMENTAL

Isitol®

Intervention Type: DIETARY_SUPPLEMENT

1 sachet of Isitol® (2,1g) contains :

• 1000 mg of myo-inositol ;
• 300 mg of N-acetyl-cystein ;
• 48.5 mg of zinc citrate (equivalent zinc pure element : 15 mg) ;
• 35 mg of D-a-tocopherol (equivalent vitamin E pure element : 12 mg) ;
• 16 mg of vitamin B3 ;
• 1.8 mg of pyridoxin hydrochloride (equivalent vitamin B6 pure element : 1.4 mg) ;
• 1.4 mg of vitamin B2 ;
• 0.37 mg of (6S)-5-methyltetrahydrofolic acid, glucosamine salt (equivalent vitamin B9 pure element : 0.2 mg).

Sachets are packaged in box of 30.

Placebo treated group

36 eligible males between 20 and 45 yo. (included limits) will take 1 sachet of placebo per day during 16 (± 2) weeks. The sachet of powder is to dissolve in a glass of water or directly in mouth.

1 sachet of placebo (2,1g) contains only excipients used in Isitol® and excipients to get similar organoleptic aspect (maltodextrin, sucralose, silicon dioxide, magnesium carbonate, citric acid and beta-carotene).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

1 sachet of placebo (2,1g) contains :

• 1765.1 of maltodextrin ;
• 300 mg of magnesium carbonate ;
• 40 mg of citric acid ;
• 5.3 mg of beta-carotene ;
• 2.16 mg of silicon dioxide ;
• 1.44 mg of sucralose.

Sachets are packaged in box of 30.

Interventions

Isitol®

1 sachet of Isitol® (2,1g) contains :

• 1000 mg of myo-inositol ;
• 300 mg of N-acetyl-cystein ;
• 48.5 mg of zinc citrate (equivalent zinc pure element : 15 mg) ;
• 35 mg of D-a-tocopherol (equivalent vitamin E pure element : 12 mg) ;
• 16 mg of vitamin B3 ;
• 1.8 mg of pyridoxin hydrochloride (equivalent vitamin B6 pure element : 1.4 mg) ;
• 1.4 mg of vitamin B2 ;
• 0.37 mg of (6S)-5-methyltetrahydrofolic acid, glucosamine salt (equivalent vitamin B9 pure element : 0.2 mg).

Sachets are packaged in box of 30.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

1 sachet of placebo (2,1g) contains :

• 1765.1 of maltodextrin ;
• 300 mg of magnesium carbonate ;
• 40 mg of citric acid ;
• 5.3 mg of beta-carotene ;
• 2.16 mg of silicon dioxide ;
• 1.44 mg of sucralose.

Sachets are packaged in box of 30.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Sperm DNA fragmentation rate ≥ 30 %

Exclusion Criteria

• Positive semen culture

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Laboratoire Drouot

UNKNOWN

Sponsor Role: collaborator

GYNOV

INDUSTRY

Sponsor Role: lead

Responsible Party

GYNOV

Chief Executive Officer

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nino-Guy Cassuto, PharmD

Role: PRINCIPAL_INVESTIGATOR

Laboratoire Drouot

Locations

Laboratoire Drouot

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Pierre-Yves Mousset, MD

Role: CONTACT

py.mousset@gynov.com

616310400 ext. +33

Axel Dries, Master

Role: CONTACT

a.dries@gynov.com

636630660 ext. +33

Facility Contacts

Axel Dries, Master

Role: primary

a.dries@gynov.com

+33636630660 ext. +33547742633

Pierre-Yves Mousset, MD

Role: backup

py.mousset@gynov.com

+33616310400 ext. +33547742633

Other Identifiers

2020-A02402-37

Identifier Type: -

Identifier Source: org_study_id