Choline Dehydrogenase and Sperm Function: Effects of Betaine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Change in sperm motility from baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •Cystathionine-beta-synthase (CBS) deficiency
- •Currently taking betaine supplements
- •Currently receiving chemotherapy, radiation or any gonadotoxic drug
- •Female gender
研究组 & 干预措施
Betaine supplement
Will use powdered betaine (BetaPower, Dupont Nutrition) that is commercially available for food uses. This powder will be delivered as capsules containing 0.5 gram of powdered betaine which will be administered as eleven capsules twice per day (6 in the morning, 5 in the evening) for a daily total of 6 grams of betaine.
干预措施: Betaine supplement (Drug)
结局指标
主要结局
Change in sperm motility from baseline
时间窗: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Assessed using Computer-Aided Sperm Analysis methodology
Change in sperm count from baseline
时间窗: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Change in sperm mitochondrial function from baseline
时间窗: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Using Seahorse biochemical function assessment
Change in sperm ultrastructure from baseline
时间窗: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Using light and transmission electron microscopy
Change in sperm choline dehydrogenase concentration from baseline
时间窗: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Assessed by Western Blot analysis
Change in sperm betaine concentration from baseline
时间窗: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
次要结局
- Change in aspartate transaminase concentration from baseline(At 0,10, 30, 50, and 75 days on treatment)
- Change in lactic dehydrogenase concentration from baseline(At 0, 10, 30, 50, and 75 days on treatment)
- Change in uric acid concentration from baseline(At 0, 10, 30, 50, and 75 days on treatment)
- Betaine intake(At screening and every 21 days during the study)
- Change in complete blood count from baseline(At 0, 10, 30, 50, and 75 days on treatment)
- Change in alkaline phosphatase concentration from baseline(At 0, 10, 30, 50, and 75 days on treatment)
- Change in bilirubin concentration from baseline(At 0, 10, 30, 50, and 75 days on treatment)
- Change in blood urea nitrogen concentration from baseline(At 0, 10, 30, 50, and 75 days on treatment)
- Change in creatinine concentration from baseline(At 0, 10, 30, 50, and 75 days on treatment)
- Change in urinalysis parameters from baseline(At 0, 10, 30, 50, and 75 days on treatment)