Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676Phase 1NCT02122211
Choline Dehydrogenase and Sperm Function: Effects of Betaine
A Phase 1 study testing Betaine supplement in people with Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676 and Male Infertility, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676, Male Infertility
- What is being tested?
- Betaine supplement
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- Cystathionine-beta-synthase (CBS) deficiency
- Currently taking betaine supplements
- Currently receiving chemotherapy, radiation or any gonadotoxic drug
- Female gender
Trial locations and contacts
1 site in 1 country.
United States1 site
UNC Nutrition Research Institute
Kannapolis, North Carolina, 28081
About this study
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.
Read the 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.
- Being tested
- Betaine supplement
- Keywords
- Sperm motility
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Betaine supplementDrug
Also called BetaPower (Dupont Nutrition)
| Study group | Role | What they receive |
|---|---|---|
| Betaine supplement | Experimental | 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. Receives: Drug: Betaine supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in sperm motility from baseline
Assessed using Computer-Aided Sperm Analysis methodology
Measured: 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
Measured: 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
Using Seahorse biochemical function assessment
Measured: 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
Using light and transmission electron microscopy
Measured: 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
Assessed by Western Blot analysis
Measured: 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
Measured: On day zero, day 10, day 30, day 50 and at the end of the 75 day treatment period
Secondary outcomes (10)
Betaine intake
Assessed using 3-day food records
Measured: At screening and every 21 days during the study
Change in complete blood count from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Change in uric acid concentration from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Change in alkaline phosphatase concentration from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Change in aspartate transaminase concentration from baseline
Measured: At 0,10, 30, 50, and 75 days on treatment
Change in lactic dehydrogenase concentration from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Change in bilirubin concentration from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Change in blood urea nitrogen concentration from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Change in creatinine concentration from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Change in urinalysis parameters from baseline
Measured: At 0, 10, 30, 50, and 75 days on treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2014 (estimated)
- Study startApr 2014
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676Studies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven Zeisel, MD, PhD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02122211
- Sponsor's protocol ID
- 13-2424
- Status last verified
- Sep 2016
- First submitted
- 17 Apr 2014
- Last updated
- 8 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22558321
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Choline Dehydrogenase and Sperm Function: Effects of Betaine
- ClinicalTrials.gov ID
- NCT02122211
- Acronym / sponsor ID
- 13-2424
- Keywords
- Sperm motility
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 24 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Betaine supplement | Experimental | Drug: Betaine supplementWill 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- Cystathionine-beta-synthase (CBS) deficiency
- Currently taking betaine supplements
- Currently receiving chemotherapy, radiation or any gonadotoxic drug
- Female gender
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Betaine supplementAlso: BetaPower (Dupont Nutrition) | Drug | Betaine supplement |
Primary outcome
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
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
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
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
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
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
10 secondary outcomes
Betaine intake
Time frame: 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
Change in uric acid concentration from baseline
Time frame: 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
Change in aspartate transaminase concentration from baseline
Time frame: 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
Change in bilirubin concentration from baseline
Time frame: 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
Change in creatinine concentration from baseline
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2016.
- Background: PubMed 22558321Johnson 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Zeisel, MD, PhD principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Betaine supplement in people with Men Carrying 2 Minor Alleles for Choline Dehydrogenase rs12676 and Male Infertility, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02122211, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2016.