Clinical trial NCT02122211: Choline Dehydrogenase and Sperm Function: Effects of Betaine
Official title: Choline Dehydrogenase and Sperm Function: Effects of Betaine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676
Male Infertility
Keywords: Sperm motility
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2014-04-24
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in sperm motility from baseline
timeFrame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
measure: Change in sperm count from baseline
timeFrame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
measure: Change in sperm mitochondrial function from baseline
timeFrame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
measure: Change in sperm ultrastructure from baseline
timeFrame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
measure: Change in sperm choline dehydrogenase concentration from baseline
timeFrame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
measure: Change in sperm betaine concentration from baseline
timeFrame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Secondary outcomes:
measure: Betaine intake
timeFrame: At screening and every 21 days during the study
measure: Change in complete blood count from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
measure: Change in uric acid concentration from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
measure: Change in alkaline phosphatase concentration from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
measure: Change in aspartate transaminase concentration from baseline
timeFrame: At 0,10, 30, 50, and 75 days on treatment
measure: Change in lactic dehydrogenase concentration from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
measure: Change in bilirubin concentration from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
measure: Change in blood urea nitrogen concentration from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
measure: Change in creatinine concentration from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
measure: Change in urinalysis parameters from baseline
timeFrame: At 0, 10, 30, 50, and 75 days on treatment
Other outcomes:
Locations:
city: Kannapolis
country: United States
facility: UNC Nutrition Research Institute
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Steven Zeisel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.