Postmenopausal WomenNCT00065546
Human Requirements for the Nutrient Choline
A study testing Estrogen plus choline depletion diet and Pre-menopausal women with SNPs given a low choline diet in people with Postmenopausal Women, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this study is to increase our understanding of how much choline humans need to get from their diet. Choline is an essential nutrient found in many foods, including eggs and milk. In addition to dietary sources, choline can be made in the liver. Read more about this study
- Who is it for?
- Ages 18 to 85 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postmenopausal Women
- What is being tested?
- Estrogen plus choline depletion diet and Pre-menopausal women with SNPs given a low choline diet
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Jan 2012
- Phase
- Interventional
- 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 85 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy
- Non-smoker
- BMI between 18 and 34
- Normal mammogram in last 12 months (post-menopausal women only)
Who cannot join
- Hormone or estrogen therapy
- Allergic to soy, eggs, wheat
- History of breast, uterine, or other estrogen-dependent cancer
- Liver or kidney problems
- History of circulation, bleeding, or blood-clotting disorder
- Anemia or evidence of iron overload
Show all 12Show fewer
- Hyperthyroidism, neurological disorder, or autoimmune disease
- Diabetes controlled by insulin
- Positive serology for HIV or Hepatitis B or C
- Alcohol or illegal drug misuse/abuse
- Pacemaker, aneurysm clip, cardiac heart valve, mechanical devices/implants
- Other metal in body (i.e. injured by a BB, shrapnel, or metallic object)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599
About this study
The purpose of this study is to increase our understanding of how much choline humans need to get from their diet. Choline is an essential nutrient found in many foods, including eggs and milk. In addition to dietary sources, choline can be made in the liver. Choline is important in making membranes or wrappers for all the cells in the body and for making chemicals that allow nerve cells to work properly. In a previous study we found that the dietary requirement for choline varies greatly from person to person. This was caused, in part, by how much estrogen a person has and their genetic makeup. We are conducting this study to explore how estrogen levels and specific differences in genes influence choline requirements so that we can refine the dietary recommendations for this nutrient.
Read the detailed description
Choline is an essential nutrient essential used for the structural integrity and signaling functions of cell membranes, cholinergic neurotransmission, and lipid transport/metabolism. Choline is obtained from the diet and from endogenous biosynthesis catalyzed by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). The major premise for this proposal is that humans require a dietary source of choline and that this requirement has significant individual variation and is modulated by estrogen and common genetic polymorphisms. The promoter of the PEMT gene is estrogen responsive, and we hypothesize that estrogen status influences the dietary requirement for choline. We identified other common single nucleotide polymorphisms (SNPs) that increase or decrease the likelihood that a human will develop organ dysfunction when fed a low choline diet. Experiments are proposed that will refine our understanding of estrogen-mediated induction of the PEMT promoter; determine whether postmenopausal women treated with estrogen have a decreased susceptibility to developing organ dysfunction associated with choline deficiency; determine the prevalence of SNPs that increase susceptibility to choline deficiency in the population and examine dietary choline requirements in humans with these SNPs.
- Conditions
- Postmenopausal Women
- Being tested
- Estrogen plus choline depletion diet, Placebo plus choline depletion diet, Pre-menopausal women with SNPs given a low choline diet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estrogen plus choline depletion dietOther
Post-menopausal subjects receive estrogen and are then challenged with a low choline diet to determine if estrogen protects them from induction of choline deficiency.
Placebo plus choline depletion dietOther
Post-menopausal women are randomized to receive a placebo and are then subjected to a low choline diet to determine if clinical signs of choline deficiency can be induced.
Pre-menopausal women with SNPs given a low choline dietOther
Pre-menopausal women with specific genetic polymorphisms in genes related to choline metabolism are placed on a choline depletion diet to determine if the SNPs increase or decrease the risk of diet-induced choline deficiency.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Post-menopausal women randomized to receive estrogen replacement therapy. Receives: Other: Estrogen plus choline depletion diet |
| 2 | Placebo comparator | Post-menopausal women randomized to receive a placebo. Receives: Other: Placebo plus choline depletion diet |
| 3 | Experimental | Pre-menopausal women with specific genetic variants. Receives: Other: Pre-menopausal women with SNPs given a low choline diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of liver or muscle dysfunction (based on elevations in CPK, AST, ALT), or increased liver fat (measured by liver MRI)
Measured: Labs measured every 3-4 days throughout 62-day trial. Liver MRI performed on study days 1, 10, 31, 52, 62.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2003 (estimated)
- Study startJun 2007
- Primary completionSep 2009
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal WomenStudies of the same condition, open and under way.
- 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 N/A
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Zeisel, University of North Carolina, Chapel Hill
- Investigators
- Steven H Zeisel, MD, PhD, Principal investigator, University of North Carolina, Chapel HillLeslie M Fischer, PhD, MPH, RD, Study director, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00065546
- Sponsor's protocol ID
- DK55865
- Other IDs
- R01DK055865
- Status last verified
- Jan 2012
- First submitted
- 28 Jul 2003
- Last updated
- 6 Jan 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
da Costa KA, Corbin KD, Niculescu MD, Galanko JA, Zeisel SH. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. FASEB J. 2014 Jul;28(7):2970-8. doi: 10.1096/fj.14-249557. Epub 2014 Mar 26.
PubMed 24671709da Costa KA, Sanders LM, Fischer LM, Zeisel SH. Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans. Am J Clin Nutr. 2011 May;93(5):968-74. doi: 10.3945/ajcn.110.011064. Epub 2011 Mar 16.
PubMed 21411618Fischer LM, da Costa KA, Kwock L, Galanko J, Zeisel SH. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010 Nov;92(5):1113-9. doi: 10.3945/ajcn.2010.30064. Epub 2010 Sep 22.
PubMed 20861172
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Requirements for the Nutrient Choline
- ClinicalTrials.gov ID
- NCT00065546
- Acronym / sponsor ID
- DK55865
- Conditions
- Postmenopausal Women
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jun 2007
- Primary completion
- Sep 2009 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 31 Jul 2003 (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 purpose of this study is to increase our understanding of how much choline humans need to get from their diet. Choline is an essential nutrient found in many foods, including eggs and milk. In addition to dietary sources, choline can be made in the liver. Choline is important in making membranes or wrappers for all the cells in the body and for making chemicals that allow nerve cells to work properly. In a previous study we found that the dietary requirement for choline varies greatly from person to person. This was caused, in part, by how much estrogen a person has and their genetic makeup. We are conducting this study to explore how estrogen levels and specific differences in genes influence choline requirements so that we can refine the dietary recommendations for this nutrient.
Detailed description
Choline is an essential nutrient essential used for the structural integrity and signaling functions of cell membranes, cholinergic neurotransmission, and lipid transport/metabolism. Choline is obtained from the diet and from endogenous biosynthesis catalyzed by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). The major premise for this proposal is that humans require a dietary source of choline and that this requirement has significant individual variation and is modulated by estrogen and common genetic polymorphisms. The promoter of the PEMT gene is estrogen responsive, and we hypothesize that estrogen status influences the dietary requirement for choline. We identified other common single nucleotide polymorphisms (SNPs) that increase or decrease the likelihood that a human will develop organ dysfunction when fed a low choline diet. Experiments are proposed that will refine our understanding of estrogen-mediated induction of the PEMT promoter; determine whether postmenopausal women treated with estrogen have a decreased susceptibility to developing organ dysfunction associated with choline deficiency; determine the prevalence of SNPs that increase susceptibility to choline deficiency in the population and examine dietary choline requirements in humans with these SNPs.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Other: Estrogen plus choline depletion dietPost-menopausal women randomized to receive estrogen replacement therapy. |
| 2 | Placebo comparator | Other: Placebo plus choline depletion dietPost-menopausal women randomized to receive a placebo. |
| 3 | Experimental | Other: Pre-menopausal women with SNPs given a low choline dietPre-menopausal women with specific genetic variants. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy
- Non-smoker
- BMI between 18 and 34
- Normal mammogram in last 12 months (post-menopausal women only)
Key exclusion criteria (12 listed)
- Hormone or estrogen therapy
- Allergic to soy, eggs, wheat
- History of breast, uterine, or other estrogen-dependent cancer
- Liver or kidney problems
- History of circulation, bleeding, or blood-clotting disorder
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 |
|---|---|---|
| Estrogen plus choline depletion dietPost-menopausal subjects receive estrogen and are then challenged with a low choline diet to determine if estrogen protects them from induction of choline deficiency. | Other | 1 |
| Placebo plus choline depletion dietPost-menopausal women are randomized to receive a placebo and are then subjected to a low choline diet to determine if clinical signs of choline deficiency can be induced. | Other | 2 |
| Pre-menopausal women with SNPs given a low choline dietPre-menopausal women with specific genetic polymorphisms in genes related to choline metabolism are placed on a choline depletion diet to determine if the SNPs increase or decrease the risk of diet-induced choline deficiency. | Other | 3 |
Primary outcome
Evidence of liver or muscle dysfunction (based on elevations in CPK, AST, ALT), or increased liver fat (measured by liver MRI)
Time frame: Labs measured every 3-4 days throughout 62-day trial. Liver MRI performed on study days 1, 10, 31, 52, 62.
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 6 Jan 2012.
- Derived from this study: PubMed 24671709da Costa KA, Corbin KD, Niculescu MD, Galanko JA, Zeisel SH. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. FASEB J. 2014 Jul;28(7):2970-8. doi: 10.1096/fj.14-249557. Epub 2014 Mar 26.
- Derived from this study: PubMed 21411618da Costa KA, Sanders LM, Fischer LM, Zeisel SH. Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans. Am J Clin Nutr. 2011 May;93(5):968-74. doi: 10.3945/ajcn.110.011064. Epub 2011 Mar 16.
- Derived from this study: PubMed 20861172Fischer LM, da Costa KA, Kwock L, Galanko J, Zeisel SH. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010 Nov;92(5):1113-9. doi: 10.3945/ajcn.2010.30064. Epub 2010 Sep 22.
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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 H Zeisel, MD, PhD principal investigator
University of North Carolina, Chapel Hill
Leslie M Fischer, PhD, MPH, RD study director
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Estrogen plus choline depletion diet and Pre-menopausal women with SNPs given a low choline diet in people with Postmenopausal Women, 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 4 inclusion and 12 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 6 Jan 2012. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Evidence of liver or muscle dysfunction (based on elevations in CPK, AST, ALT), or increased liver fat (measured by liver MRI) (time frame: Labs measured every 3-4 days throughout 62-day trial. Liver MRI performed on study days 1, 10, 31, 52, 62.). 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 NCT00065546, which also lists 3 linked publications.
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 6 Jan 2012.