Choline Dehydrogenase and Sperm Function: Effects of Betaine

September 7, 2016 updated by: University of North Carolina, Chapel Hill
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Kannapolis, North Carolina, United States, 28081
        • UNC Nutrition Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • BetaPower (Dupont Nutrition)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
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
Time Frame: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Using Seahorse biochemical function assessment
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
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
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
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
Assessed by Western Blot analysis
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
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
On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Betaine intake
Time Frame: At screening and every 21 days during the study
Assessed using 3-day food records
At screening and every 21 days during the study
Change in complete blood count from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment
Change in uric acid concentration from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment
Change in alkaline phosphatase concentration from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment
Change in aspartate transaminase concentration from baseline
Time Frame: At 0,10, 30, 50, and 75 days on treatment
At 0,10, 30, 50, and 75 days on treatment
Change in lactic dehydrogenase concentration from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment
Change in bilirubin concentration from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment
Change in blood urea nitrogen concentration from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment
Change in creatinine concentration from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment
Change in urinalysis parameters from baseline
Time Frame: At 0, 10, 30, 50, and 75 days on treatment
At 0, 10, 30, 50, and 75 days on treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Investigators

  • Principal Investigator: Steven Zeisel, MD, PhD, University of North Carolina

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (ACTUAL)

July 1, 2016

Study Completion (ACTUAL)

July 1, 2016

Study Registration Dates

First Submitted

April 17, 2014

First Submitted That Met QC Criteria

April 22, 2014

First Posted (ESTIMATE)

April 24, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

September 8, 2016

Last Update Submitted That Met QC Criteria

September 7, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-2424

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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