Glycosphingolipid Inhibition and Spermatogenesis in Man: A Pilot Study (MIG 2)

Contraception Clinical Trial

— MIG-2  

Official title:

Glycosphingolipid Inhibition and Spermatogenesis in Man: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00194649
• Other study ID #: 04-3806-D
• Secondary ID: U54HD042454
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: September 18, 2008
• Start date: June 2005
• Est. completion date: January 2006

Study information

• Verified date: September 2008
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to help in the development of safe, effective and reversible male contraception. We are examining the impact of the drug Miglustat on sperm production in normal men.

We want to see if Miglustat will inhibit sperm production in men and act as a reversible male contraceptive, as a study in mice administered Miglustat showed a reversible inhibition of sperm production. We believe Miglustat may have some potential as a safe, reversible male contraceptive.

Description:

Glycosphingolipids (GSL) are a main constituent of the sperm cell membrane in mammals. Male mice deficient in enzymes involved in GSL synthesis have severely impaired fertility and knockout mice are infertile. Recently, it was demonstrated that administration to mice of an inhibitor of ceramide-specific glycosyltransferase, the first step in the biosynthetic pathway of GSL formation, resulted in reversible infertility without discernable adverse side effects. This inhibitor was Miglustat, which is an alkylated imino sugar. The impact of Miglustat therapy on human spermatogenesis is unknown. If the effects on sperm morphology and motility are similar to those observed in mice, Miglustat or other GSL inhibitors might have potential utility as non-hormonal male contraceptives.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: January 2006
• Est. primary completion date: January 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy male, normal lab test

Exclusion Criteria:

• Abnormal lab test, history or evidence of significant chronic or acute medical illness, previous or current ethanol or anabolic steroid abuse.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Contraception

Intervention

Drug:
• Miglustat (Zavesca)
100 mg Miglustat BID (twice daily) for six weeks

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (8)

Amory JK, Muller CH, Page ST, Leifke E, Pagel ER, Bhandari A, Subramanyam B, Bone W, Radlmaier A, Bremner WJ. Miglustat has no apparent effect on spermatogenesis in normal men. Hum Reprod. 2007 Mar;22(3):702-7. Epub 2006 Oct 25. — View Citation

Beutler E. Gaucher disease. Curr Opin Hematol. 1997 Jan;4(1):19-23. Review. — View Citation

Fujimoto H, Tadano-Aritomi K, Tokumasu A, Ito K, Hikita T, Suzuki K, Ishizuka I. Requirement of seminolipid in spermatogenesis revealed by UDP-galactose: Ceramide galactosyltransferase-deficient mice. J Biol Chem. 2000 Jul 28;275(30):22623-6. — View Citation

Honke K, Hirahara Y, Dupree J, Suzuki K, Popko B, Fukushima K, Fukushima J, Nagasawa T, Yoshida N, Wada Y, Taniguchi N. Paranodal junction formation and spermatogenesis require sulfoglycolipids. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4227-32. Epub 2002 Mar 26. — View Citation

Platt FM, Neises GR, Karlsson GB, Dwek RA, Butters TD. N-butyldeoxygalactonojirimycin inhibits glycolipid biosynthesis but does not affect N-linked oligosaccharide processing. J Biol Chem. 1994 Oct 28;269(43):27108-14. — View Citation

Ritter G, Krause W, Geyer R, Stirm S, Wiegandt H. Glycosphingolipid composition of human semen. Arch Biochem Biophys. 1987 Sep;257(2):370-8. — View Citation

Takamiya K, Yamamoto A, Furukawa K, Zhao J, Fukumoto S, Yamashiro S, Okada M, Haraguchi M, Shin M, Kishikawa M, Shiku H, Aizawa S, Furukawa K. Complex gangliosides are essential in spermatogenesis of mice: possible roles in the transport of testosterone. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12147-52. — View Citation

van der Spoel AC, Jeyakumar M, Butters TD, Charlton HM, Moore HD, Dwek RA, Platt FM. Reversible infertility in male mice after oral administration of alkylated imino sugars: a nonhormonal approach to male contraception. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17173-8. Epub 2002 Dec 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The impact of GSL inhibition on human spermatogenesis, if impairment is seen with Miglustat administration, larger contraceptive efficacy studies of Miglustat or other inhibitors of GSL's will be performed.		3 months	No
Secondary	Safety		3 months	Yes

External Links

•   http://depts.washington.edu/popctr