Verified October 2016 by University Hospital, Rouen
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen
ClinicalTrials.gov Identifier:
NCT02932527
First received: October 7, 2016
Last updated: October 11, 2016
Last verified: October 2016
Lifestyle and environmental factors can disrupt development and testicular function. In France, cannabis is the most widely used illicit substance and about 8% of adults between 18 and 64 years smoke cannabis at least once a year, and mostly men under 45 years. Endocannabinoids are lipid mediators that share some effects with the active ingredients of cannabis. Cannabis and endocannabinoids act via two types of endogenous receptors which were detected at different levels of the reproductive system and are involved in the central and local regulation of the gonad. Cannabis use may alter the normal regulation of the endocannabinoid system. In males, the regulation of the endocannabinoid system is critical for Sertoli and Leydig cells functions, germ cell differentiation, maturation of sperm nucleus and sperm quality. The cannabis can have a negative impact on sperm parameters, capacitation and acrosome reaction. Cannabinoids may decrease testosterone synthesis and induce apoptosis of Sertoli cells. Studies on the effect of cannabinoids on male fertility are scarce or nonexistent in infertile men because of ethical considerations and bias due to consumption often underreported. Investigators hypothesized that cannabis use may alter sperm nuclear quality. Investigators want to explore this hypothesis conducting a multicentric prospective study exposed/non-exposed in infertile men who are consulting for Medically Assisted Reproductive Technologies (ART). To reach this study, it is planned to include a total of 200 subjects taking into account any exclusions.
| Teratozoospermia | Behavioral: Questionnaire about cannabis consumption Procedure: blood intake Procedure: Semen samples collection |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Diagnostic |
| Official Title: | Effect of Cannabis Consumption on Sperm Nuclear Quality in Infertile Men : a Prospective Exposed / Unexposed Study |
- Evaluation of consumption level [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
Consumption level are evaluated for patients exposed to cannabis, using questionnaire
- Evaluation of cannabinoids level in blood [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
cannabinoids levels in blood are evaluated for patients exposed and not exposed to cannabis
- Total sperm count [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
- Percentage of mobile spermatozoa [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
- Percentage of morphologically abnormal spermatozoa [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
- Mean vacuole area threshold [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
Mean vacuole area threshold is measured with Receiver Operating Characteristic curves
- Correlation coefficient between vacuole areas and sperm DNA fragmentation [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
Correlation coefficient between vacuole areas and sperm DNA fragmentation are evaluated by TUNEL analysis
- Correlation coefficient between vacuole areas and abnormal chromatin condensation [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
Correlation coefficient between vacuole areas and abnormal chromatin condensation is evaluated by aniline blue staining
- Correlation coefficient between vacuole areas and telomere number, distribution and length [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
Correlation coefficient between vacuole areas and telomere number, distribution and length is evaluated by quantitative FISH
| Estimated Enrollment: | 200 |
| Study Start Date: | December 2016 |
| Estimated Study Completion Date: | December 2019 |
| Estimated Primary Completion Date: | December 2019 (Final data collection date for primary outcome measure) |
| Experimental: infertile men exposed to cannabis
Male with isolated teratozoospermia or associated with asthenozoospermia and / or oligozoospermia and / or necrozoospermia defined according to WHO recommendations (WHO guidelines, 2010) and the David amended classification (Auger et al., 2001) with normal constitutional karyotype (46, XY) exposed to cannabis; The exposure to cannabis is not an intervention in the study but is a pre-condition for inclusion. Blood intake and semen samples collection are done. Questionnaire about cannabis consumption are assessed to patient. |
Behavioral: Questionnaire about cannabis consumption
Questionnaire about cannabis consumption will be assessed to infertile male exposed to cannabis and infertile male not exposed to cannabis. Procedure: blood intake blood intake is done for infertile male exposed and infertile male not exposed. Procedure: Semen samples collection Semen samples are collected for infertile male exposed and infertile male not exposed. |
| infertile men not exposed to cannabis
Male with isolated teratozoospermia or associated with asthenozoospermia and / or oligozoospermia and / or necrozoospermia defined according to WHO recommendations (WHO guidelines, 2010) and the David amended classification (Auger et al., 2001) with normal constitutional karyotype (46, XY) not exposed to cannabis; The exposure to cannabis is not an intervention in the study but is a pre-condition for inclusion. Blood intake and semen samples collection are done. Questionnaire about cannabis consumption are assessed to patient. |
Behavioral: Questionnaire about cannabis consumption
Questionnaire about cannabis consumption will be assessed to infertile male exposed to cannabis and infertile male not exposed to cannabis. Procedure: blood intake blood intake is done for infertile male exposed and infertile male not exposed. Procedure: Semen samples collection Semen samples are collected for infertile male exposed and infertile male not exposed. |
| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male Patient,
- Patient age ≥ 18 years,
- Infertile patient with isolated teratozoospermia or associated with asthenozoospermia and / or oligozoospermia and / or necrozoospermia, defined according to WHO recommendations (WHO guidelines, 2010) and the David amended classification (Auger et al, 2001) for teratozoospermia
- Patient with normal constitutional karyotype (46, XY).
- Smoking tobacco,
- Drinking ≤ 20 g (2 units) / day,
- Patient exposed : Cannabis user for over 3 months and consuming at least weekly (≥ 1 / week) [questionnaire and positive blood detection of Delta-9-Tetrahydrocannabinol (THC) and / or its derivatives (11-hydroxy-THC and 11-nor-9-carboxy-THC)].
- Unexposed : No cannabis user (questionnaire and negative blood detection of Delta-9-THC and its derivatives) matched for age (+/- 2.5 years) with exposed patients included,
Exclusion Criteria:
- Patient age > 60 years
- Patient with azoospermia
- Patient previously exposed to gonadotoxic treatment (chemotherapy, radiotherapy, androgen therapy and other gonadotoxic treatments),
- Patient with professional toxic exposure,
- Patient consuming other recreational drugs,
- Patient with severely impaired sperm parameters and sperm counts <1 million,
Please refer to this study by its ClinicalTrials.gov identifier: NCT02932527
| Caen University Hospital | |
| Caen, France | |
| Contact: Emeline BOVET-COURTOIS, MD | |
| Principal Investigator: Emeline BOVET-COURTOIS, MD | |
| Lille University Hospital | |
| Lille, France | |
| Contact: Anne-Laure BARBOTIN, MD | |
| Principal Investigator: Anne-Laure BARBOTIN, MD | |
| Rouen University Hospital | |
| Rouen, France | |
| Contact: France VERHAEGHE, MD France.Verhaeghe@nullchu-rouen.fr | |
| Principal Investigator: France VERHAEGHE, MD | |
| Sub-Investigator: Nathalie RIVES, Pr | |
University Hospital, Rouen
| Principal Investigator: | France VERHAEGHE, MD | Rouen University Hospital |
| Responsible Party: | University Hospital, Rouen |
| ClinicalTrials.gov Identifier: | NCT02932527 History of Changes |
| Other Study ID Numbers: | 2015/209/HP |
| Study First Received: | October 7, 2016 |
| Last Updated: | October 11, 2016 |
| Health Authority: | France: Agence Nationale de Sécurité du Médicament et des produits de santé |
| Individual Participant Data | |
| Plan to Share IPD: | No |
Keywords provided by University Hospital, Rouen:
Additional relevant MeSH terms:
| Marijuana Abuse Substance-Related Disorders Chemically-Induced Disorders Mental Disorders |
ClinicalTrials.gov processed this record on October 13, 2016