Effect of Cannabis Consumption on Sperm Nuclear Quality in Infertile Men (CANNASPERM)

Effect of Cannabis Consumption on Sperm Nuclear Quality in Infertile Men : a Prospective Exposed / Unexposed Study

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.

Study Overview

• Status: Unknown
• Conditions: Teratozoospermia
• Intervention / Treatment: Behavioral: Questionnaire about cannabis consumption; Procedure: blood intake; Procedure: Semen samples collection

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: France VERHAEGHE, MD; Phone Number: 8990 +3323288; Email: France.Verhaeghe@chu-rouen.fr

Study Locations

• France
  • Caen, France
    • Recruiting
    • CAEN University Hospital
    • Contact: Emeline BOVET-COURTOIS, MD
    • Principal Investigator: Emeline BOVET-COURTOIS, MD
  • Lille, France
    • Recruiting
    • Lille University Hospital
    • Contact: Anne-Laure BARBOTIN, MD
    • Principal Investigator: Anne-Laure BARBOTIN, MD
  • Rouen, France
    • Recruiting
    • ROUEN university hospital
    • Contact: France VERHAEGHE, MD; Email: France.Verhaeghe@chu-rouen.fr
    • Principal Investigator: France VERHAEGHE, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of spermatic aneuploidy rate	Spermatic aneuploidy rate is evaluated for patients exposed and not exposed to cannabis	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of consumption level	Consumption level are evaluated for patients exposed to cannabis, using questionnaire	Day 1
Evaluation of cannabinoids level in blood	cannabinoids levels in blood are evaluated for patients exposed and not exposed to cannabis	Day 1
Total sperm count		Day 1
Percentage of mobile spermatozoa		Day 1
Percentage of morphologically abnormal spermatozoa		Day 1
Mean vacuole area threshold	Mean vacuole area threshold is measured with Receiver Operating Characteristic curves	Day 1
Correlation coefficient between vacuole areas and sperm DNA fragmentation	Correlation coefficient between vacuole areas and sperm DNA fragmentation are evaluated by TUNEL analysis	Day 1
Correlation coefficient between vacuole areas and abnormal chromatin condensation	Correlation coefficient between vacuole areas and abnormal chromatin condensation is evaluated by aniline blue staining	Day 1
Correlation coefficient between vacuole areas and telomere number, distribution and length	Correlation coefficient between vacuole areas and telomere number, distribution and length is evaluated by quantitative FISH	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Investigators: Principal Investigator: France VERHAEGHE, MD, ROUEN university hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2017
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: October 7, 2016
• First Submitted That Met QC Criteria: October 11, 2016
• First Posted (Estimate): October 13, 2016

Study Record Updates

• Last Update Posted (Actual): May 17, 2018
• Last Update Submitted That Met QC Criteria: May 14, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: cannabis
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Infertility, Male; Infertility; Marijuana Abuse; Teratozoospermia
• Other Study ID Numbers: 2015/209/HP

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