Choline Dehydrogenase and Sperm Function: Effects of Betaine

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of North Carolina, Chapel Hill
Sponsor:
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02122211
First received: April 17, 2014
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676
Male Infertility
Drug: Betaine supplement
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Choline Dehydrogenase and Sperm Function: Effects of Betaine

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Change in sperm motility from baseline [ Time Frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period ] [ Designated as safety issue: No ]
    Assessed using Computer-Aided Sperm Analysis methodology

  • 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 ] [ Designated as safety issue: No ]
  • Change in sperm mitochondrial function from baseline [ Time Frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period ] [ Designated as safety issue: No ]
    Using Seahorse biochemical function assessment

  • Change in sperm ultrastructure from baseline [ Time Frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period ] [ Designated as safety issue: No ]
    Using light and transmission electron microscopy

  • Change in sperm choline dehydrogenase concentration from baseline [ Time Frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period ] [ Designated as safety issue: No ]
    Assessed by Western Blot analysis

  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Betaine intake [ Time Frame: At screening and every 21 days during the study ] [ Designated as safety issue: No ]
    Assessed using 3-day food records

  • Change in complete blood count from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in uric acid concentration from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in alkaline phosphatase concentration from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in aspartate transaminase concentration from baseline [ Time Frame: At 0,10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in lactic dehydrogenase concentration from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in bilirubin concentration from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in blood urea nitrogen concentration from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in creatinine concentration from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]
  • Change in urinalysis parameters from baseline [ Time Frame: At 0, 10, 30, 50, and 75 days on treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: April 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Betaine supplement
Other Name: BetaPower (Dupont Nutrition)

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02122211

Contacts
Contact: Tondra Blevins 704-250-5035 Sperm_Study@unc.edu
Contact: Summer Goodson 704-250-5048 summer_goodson@unc.edu

Locations
United States, North Carolina
UNC Nutrition Research Institute Recruiting
Kannapolis, North Carolina, United States, 28081
Contact: Tondra Blevins    704-250-5035    Sperm_Study@unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Steven Zeisel, MD, PhD University of North Carolina
  More Information

Publications:
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02122211     History of Changes
Other Study ID Numbers: 13-2424
Study First Received: April 17, 2014
Last Updated: April 22, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
Sperm motility

Additional relevant MeSH terms:
Infertility, Male
Infertility
Genital Diseases, Male
Genital Diseases, Female
Betaine
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents

ClinicalTrials.gov processed this record on August 21, 2014