Choline Dehydrogenase and Sperm Function: Effects of Betaine

Male Infertility Clinical Trial

Official title:

Choline Dehydrogenase and Sperm Function: Effects of Betaine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02122211
• Other study ID #: 13-2424
• Status: Completed
• Phase: Phase 1
• First received: April 17, 2014
• Last updated: September 7, 2016
• Start date: April 2014
• Est. completion date: July 2016

Study information

• Verified date: September 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The ability of sperm to swim is important for normal fertility. Men with a genetic variation in the gene coding for Choline Dehydrogenase (CHDH) have decreased energy production by sperm, and their sperm do not swim normally. The metabolic product of this gene is a nutrient called betaine (found normally in the diet as a part of many foods such as spinach, beets and grain products). This study tests whether treatment with betaine is safe and whether it can normalize energy production in sperm of these men and restore normal swimming ability.

Description:

Unidentified genetic aberrations such as single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic infertility in men. Choline dehydrogenase (encoded by CHDH) converts choline to betaine in the mitochondria. 5-9% of men have 2 alleles for a functional SNP in CHDH (rs12676), and they have low sperm adenosine triphosphate (ATP) concentrations with impaired sperm motility (asthenospermia) that should decrease fertility. Male mice in which CHDH is deleted also have very low sperm ATP, asthenospermia and are infertile. Supplementation of these mice with dietary betaine increases sperm motility and ATP concentrations.

This purpose of this study is to conduct a phase I study of betaine treatment in men with 2 minor alleles for CHDH rs12676 to determine whether betaine supplementation is safe and to obtain preliminary data on the effects of betaine on sperm mitochondrial ATP concentrations and sperm motility in these men.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 18 - 60 year old men of multiple races and ethnicities

• Estimated dietary intake of betaine of <150 mg/day

• Carrying two alleles of the rs 12676 single nucleotide polymorphism

Exclusion Criteria:

• Cystathionine-beta-synthase (CBS) deficiency

• Currently taking betaine supplements

• Currently receiving chemotherapy, radiation or any gonadotoxic drug

• Female gender

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Infertility
• Infertility, Male
• Male Infertility
• Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676

Intervention

Drug:
• Betaine supplement

Locations

Country	Name	City	State
United States	UNC Nutrition Research Institute	Kannapolis	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

References & Publications (1)

Johnson AR, Lao S, Wang T, Galanko JA, Zeisel SH. Choline dehydrogenase polymorphism rs12676 is a functional variation and is associated with changes in human sperm cell function. PLoS One. 2012;7(4):e36047. doi: 10.1371/journal.pone.0036047. Epub 2012 Apr 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in sperm motility from baseline	Assessed using Computer-Aided Sperm Analysis methodology	On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period	No
Primary	Change in sperm count from baseline		On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period	No
Primary	Change in sperm mitochondrial function from baseline	Using Seahorse biochemical function assessment	On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period	No
Primary	Change in sperm ultrastructure from baseline	Using light and transmission electron microscopy	On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period	No
Primary	Change in sperm choline dehydrogenase concentration from baseline	Assessed by Western Blot analysis	On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period	No
Primary	Change in sperm betaine concentration from baseline		On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period	No
Secondary	Betaine intake	Assessed using 3-day food records	At screening and every 21 days during the study	No
Secondary	Change in complete blood count from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in uric acid concentration from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in alkaline phosphatase concentration from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in aspartate transaminase concentration from baseline		At 0,10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in lactic dehydrogenase concentration from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in bilirubin concentration from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in blood urea nitrogen concentration from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in creatinine concentration from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes
Secondary	Change in urinalysis parameters from baseline		At 0, 10, 30, 50, and 75 days on treatment	Yes