HyperhomocysteinemiaPhase 3NCT01371357
The Effects of 8-week Choline, Betaine, and Folic Acid Supplementation on Plasma Homocysteine Concentration During Guanidinoacetic Acid Loading in Young Healthy Volunteers
A Phase 3 study testing TEST 1, TEST 2 and TEST 3 in people with Hyperhomocysteinemia, run by Center for Health Sciences, Serbia at 1 site in Serbia.
Trial summary
A methyl-group acceptor such as guanidinoacetic acid (GAA) could induce hyperhomocysteinemia with the effects of GAA expected to be dose-dependent. Due to the fact that hyperhomocysteinemia is thought to be an independent risk factor for cardiovascular and neurodegenerative diseases, different dietary agents were used… Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperhomocysteinemia
- What is being tested?
- TEST 1, TEST 2 and TEST 3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSerbia
- Study dates
- May 2011to Dec 2011
- Phase
- Phase 3
- 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 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy male and non-pregnant females
- moderately physically active
- aged 20 to 30 years
- not currently taking any dietary supplement for the past 2 months
Who cannot join
- total plasma homocysteine above 15.5 µmol/L
Trial locations and contacts
1 site in 1 country.
About this study
A methyl-group acceptor such as guanidinoacetic acid (GAA) could induce hyperhomocysteinemia with the effects of GAA expected to be dose-dependent. Due to the fact that hyperhomocysteinemia is thought to be an independent risk factor for cardiovascular and neurodegenerative diseases, different dietary agents were used in the past for the treatment of elevated total plasma homocysteine (T-HCy), e. g. betaine, choline (betaine precursor) or folic acid. In the context of GAA loading the question arises whether intake of betaine, choline (betaine precursor) or folic acid during GAA loading could affect plasma T-HCy in healthy humans. Forty healthy physically active men and women aged 20 to 30 years will take part in this GAA-controlled, double-blind and parallel-group intervention study. Subjects will be allocated to four randomly assigned trials, with treatment lasting for 8 weeks and washout period of 28 days. The 4 test treatment-groups will include TEST1 (GAA only), TEST2 (GAA, choline, B6, B12 and folic acid), TEST3 (GAA, betaine, B6, B12 and folic acid) and TEST4 (GAA, B6, B12 and folic acid). Plasma T-HCy will be the primary outcome measure assessed every second week throughout the study. Plasma B-vitamins and blood and urine metabolites (GAA, creatine, methionine, arginine) will be secondary outcome measures along with adverse-effects indicators assessed every second week throughout the study. Selected body composition indicators will be obtained at 0, 2, 8 and 12 weeks throughout the study to monitor the effects of experimental treatments on body hydration and protein synthesis. This research will test the hypothesis that a combination of GAA with homocysteine lowering nutrients attenuates the elevation of T-hcy, and will further display the size-effect of each additive used.
- Conditions
- Hyperhomocysteinemia
- Being tested
- TEST 1, TEST 2, TEST 3, TEST 4
- Keywords
- Remethylation, Human Subjects, Clinical Trial, B-vitamin, Creatine
- Medical subject headings
- Hyperhomocysteinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEST 1Drug
2.4 g/day of guanidinoacetic acid
TEST 2Drug
2.4 g/day of guanidinoacetic acid + 3.0 g/day of choline dihydrogencitrate + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid
TEST 3Drug
2.4 g/day of guanidinoacetic acid + 1.6 g/day of betaine HCl + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid
TEST 4Drug
2.4 g/day of guanidinoacetic acid + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid
| Study group | Role | What they receive |
|---|---|---|
| TEST1 | Experimental | 2.4 g/day of guanidinoacetic acid Receives: Drug: TEST 1 |
| TEST 2 | Experimental | 2.4 g/day of guanidinoacetic acid + 3.0 g/day of choline dihydrogen citrate + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid Receives: Drug: TEST 2 |
| TEST 3 | Experimental | 2.4 g/day of guanidinoacetic acid + 1.6 g/day of betaine HCl + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid Receives: Drug: TEST 3 |
| TEST 4 | Experimental | 2.4 g/day of guanidinoacetic acid + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid Receives: Drug: TEST 4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total plasma homocysteine
Measured: 3 months
Secondary outcomes (1)
Serum creatine
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2011
- Study completionDec 2011
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 HyperhomocysteinemiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Health Sciences, Serbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Assoc. Prof. Sergej M. Ostojic, MD, PhD, Center for Health Sciences, Serbia
- Investigators
- Sergej M Ostojic, MD, PhD, Principal investigator, Center for Health, Exercise and Sport Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01371357
- Sponsor's protocol ID
- BN-214E-S10
- Status last verified
- Dec 2011
- First submitted
- 9 Jun 2011
- Last updated
- 20 Dec 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005 Jul;82(1):111-7. doi: 10.1093/ajcn.82.1.111.
PubMed 16002808Setoue M, Ohuchi S, Morita T, Sugiyama K. Hyperhomocysteinemia induced by guanidinoacetic acid is effectively suppressed by choline and betaine in rats. Biosci Biotechnol Biochem. 2008 Jul;72(7):1696-703. doi: 10.1271/bbb.70791. Epub 2008 Jul 7.
PubMed 18603787Verhoef P, de Groot LC. Dietary determinants of plasma homocysteine concentrations. Semin Vasc Med. 2005 May;5(2):110-23. doi: 10.1055/s-2005-872397.
PubMed 16047264
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of 8-week Choline, Betaine, and Folic Acid Supplementation on Plasma Homocysteine Concentration During Guanidinoacetic Acid Loading in Young Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01371357
- Acronym / sponsor ID
- BN-214E-S10
- Conditions
- Hyperhomocysteinemia
- Keywords
- Remethylation, Human Subjects, Clinical Trial, B-vitamin, Creatine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Center for Health Sciences, SerbiaUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 10 Jun 2011 (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.
A methyl-group acceptor such as guanidinoacetic acid (GAA) could induce hyperhomocysteinemia with the effects of GAA expected to be dose-dependent. Due to the fact that hyperhomocysteinemia is thought to be an independent risk factor for cardiovascular and neurodegenerative diseases, different dietary agents were used in the past for the treatment of elevated total plasma homocysteine (T-HCy), e. g. betaine, choline (betaine precursor) or folic acid. In the context of GAA loading the question arises whether intake of betaine, choline (betaine precursor) or folic acid during GAA loading could affect plasma T-HCy in healthy humans. Forty healthy physically active men and women aged 20 to 30 years will take part in this GAA-controlled, double-blind and parallel-group intervention study. Subjects will be allocated to four randomly assigned trials, with treatment lasting for 8 weeks and washout period of 28 days. The 4 test treatment-groups will include TEST1 (GAA only), TEST2 (GAA, choline, B6, B12 and folic acid), TEST3 (GAA, betaine, B6, B12 and folic acid) and TEST4 (GAA, B6, B12 and folic acid). Plasma T-HCy will be the primary outcome measure assessed every second week throughout the study. Plasma B-vitamins and blood and urine metabolites (GAA, creatine, methionine, arginine) will be secondary outcome measures along with adverse-effects indicators assessed every second week throughout the study. Selected body composition indicators will be obtained at 0, 2, 8 and 12 weeks throughout the study to monitor the effects of experimental treatments on body hydration and protein synthesis. This research will test the hypothesis that a combination of GAA with homocysteine lowering nutrients attenuates the elevation of T-hcy, and will further display the size-effect of each additive used.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TEST1 | Experimental | Drug: TEST 12.4 g/day of guanidinoacetic acid |
| TEST 2 | Experimental | Drug: TEST 22.4 g/day of guanidinoacetic acid + 3.0 g/day of choline dihydrogen citrate + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid |
| TEST 3 | Experimental | Drug: TEST 32.4 g/day of guanidinoacetic acid + 1.6 g/day of betaine HCl + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid |
| TEST 4 | Experimental | Drug: TEST 42.4 g/day of guanidinoacetic acid + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- healthy male and non-pregnant females
- moderately physically active
- aged 20 to 30 years
- not currently taking any dietary supplement for the past 2 months
Key exclusion criteria (1 listed)
- total plasma homocysteine above 15.5 µmol/L
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 |
|---|---|---|
| TEST 12.4 g/day of guanidinoacetic acid | Drug | TEST1 |
| TEST 22.4 g/day of guanidinoacetic acid + 3.0 g/day of choline dihydrogencitrate + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid | Drug | TEST 2 |
| TEST 32.4 g/day of guanidinoacetic acid + 1.6 g/day of betaine HCl + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid | Drug | TEST 3 |
| TEST 42.4 g/day of guanidinoacetic acid + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid | Drug | TEST 4 |
Primary outcome
Total plasma homocysteine
Time frame: 3 months
1 secondary outcome
Serum creatine
Time frame: 3 months
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 20 Dec 2011.
- Background: PubMed 16002808Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005 Jul;82(1):111-7. doi: 10.1093/ajcn.82.1.111.
- Background: PubMed 18603787Setoue M, Ohuchi S, Morita T, Sugiyama K. Hyperhomocysteinemia induced by guanidinoacetic acid is effectively suppressed by choline and betaine in rats. Biosci Biotechnol Biochem. 2008 Jul;72(7):1696-703. doi: 10.1271/bbb.70791. Epub 2008 Jul 7.
- Background: PubMed 16047264Verhoef P, de Groot LC. Dietary determinants of plasma homocysteine concentrations. Semin Vasc Med. 2005 May;5(2):110-23. doi: 10.1055/s-2005-872397.
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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.
Sergej M Ostojic, MD, PhD principal investigator
Center for Health, Exercise and Sport Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TEST 1, TEST 2 and TEST 3 in people with Hyperhomocysteinemia, run by Center for Health Sciences, Serbia at 1 site in Serbia.
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 1 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 20 Dec 2011. 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 Serbia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Total plasma homocysteine (time frame: 3 months). 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 NCT01371357, 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 20 Dec 2011.