search
Back to results

Choline Dehydrogenase and Sperm Function: Effects of Betaine

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Betaine supplement
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676 focused on measuring Sperm motility

Eligibility Criteria

18 Years - 60 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • UNC Nutrition Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Betaine supplement

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in sperm motility from baseline
Assessed using Computer-Aided Sperm Analysis methodology
Change in sperm count from baseline
Change in sperm mitochondrial function from baseline
Using Seahorse biochemical function assessment
Change in sperm ultrastructure from baseline
Using light and transmission electron microscopy
Change in sperm choline dehydrogenase concentration from baseline
Assessed by Western Blot analysis
Change in sperm betaine concentration from baseline

Secondary Outcome Measures

Betaine intake
Assessed using 3-day food records
Change in complete blood count from baseline
Change in uric acid concentration from baseline
Change in alkaline phosphatase concentration from baseline
Change in aspartate transaminase concentration from baseline
Change in lactic dehydrogenase concentration from baseline
Change in bilirubin concentration from baseline
Change in blood urea nitrogen concentration from baseline
Change in creatinine concentration from baseline
Change in urinalysis parameters from baseline

Full Information

First Posted
April 17, 2014
Last Updated
September 7, 2016
Sponsor
University of North Carolina, Chapel Hill
search

1. Study Identification

Unique Protocol Identification Number
NCT02122211
Brief Title
Choline Dehydrogenase and Sperm Function: Effects of Betaine
Official Title
Choline Dehydrogenase and Sperm Function: Effects of Betaine
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676, Male Infertility
Keywords
Sperm motility

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Betaine supplement
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Betaine supplement
Other Intervention Name(s)
BetaPower (Dupont Nutrition)
Primary Outcome Measure Information:
Title
Change in sperm motility from baseline
Description
Assessed using Computer-Aided Sperm Analysis methodology
Time Frame
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Title
Change in sperm count from baseline
Time Frame
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Title
Change in sperm mitochondrial function from baseline
Description
Using Seahorse biochemical function assessment
Time Frame
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Title
Change in sperm ultrastructure from baseline
Description
Using light and transmission electron microscopy
Time Frame
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Title
Change in sperm choline dehydrogenase concentration from baseline
Description
Assessed by Western Blot analysis
Time Frame
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Title
Change in sperm betaine concentration from baseline
Time Frame
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Secondary Outcome Measure Information:
Title
Betaine intake
Description
Assessed using 3-day food records
Time Frame
At screening and every 21 days during the study
Title
Change in complete blood count from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment
Title
Change in uric acid concentration from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment
Title
Change in alkaline phosphatase concentration from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment
Title
Change in aspartate transaminase concentration from baseline
Time Frame
At 0,10, 30, 50, and 75 days on treatment
Title
Change in lactic dehydrogenase concentration from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment
Title
Change in bilirubin concentration from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment
Title
Change in blood urea nitrogen concentration from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment
Title
Change in creatinine concentration from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment
Title
Change in urinalysis parameters from baseline
Time Frame
At 0, 10, 30, 50, and 75 days on treatment

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Zeisel, MD, PhD
Organizational Affiliation
University of North Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
UNC Nutrition Research Institute
City
Kannapolis
State/Province
North Carolina
ZIP/Postal Code
28081
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22558321
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.
Results Reference
background

Learn more about this trial

Choline Dehydrogenase and Sperm Function: Effects of Betaine

We'll reach out to this number within 24 hrs