HomocystinuriaNCT06495567
Proof of Concept Creatine Supplementation for Homocystinuria Study
A study testing Creatine and Dietary methionine tracer and protein intake in people with Homocystinuria, run by University of British Columbia at 1 site in Canada.
Trial summary
Homocystinuria is a rare and inherited metabolic disorder, people with this condition don't have an enzyme needed to break down an amino acid called homocysteine. When the body can't break down the homocysteine made from another amino acid methionine, it becomes toxic to the heart, brain, and bones. Read more about this study
- Who is it for?
- Ages 19 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Homocystinuria
- What is being tested?
- Creatine and Dietary methionine tracer and protein intake
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteCanada
- Study dates
- 19 Aug 2024to 1 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 19 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Cis-male
- Men who are classified as normal body weight and BMI (18.5-25kg/m2)
- Free of any concurrent illness (cold, flu, vomiting etc.)
- Not be claustrophobic (we will place a clear hood, which can easily be removed, over your head for approximately 20 min to measure your energy expenditure)
- Not be enrolled in any other research studies (as this may affect our study results)
Who cannot join
- Men not in good health or have a metabolic, neurological, genetic, or immune disorder, including diabetes, hypoglycemia, hypertension and current or past history of kidney disease
- Men who have food allergies/sensitivities/intolerances to egg, corn, diary etc.
- Men who have current or recent past history of ingesting creatine supplements
- Men who are smokers
- Men who are following a non-traditional dietary pattern (e.g. Keto diet, Atkins diet, paleo diet, intermittent fasting, strict vegan, calorie restricted diet etc.)
Trial locations and contacts
1 site in 1 country.
Canada1 site
BC Children's Hospital Research Institute, University of British Columbia
Vancouver, British Columbia, V5Z4H4
About this study
Official title: Creatine Supplementation for CBS-related Homocystinuria: A Proof-of-concept Study in Healthy Adults
Homocystinuria is a rare and inherited metabolic disorder, people with this condition don't have an enzyme needed to break down an amino acid called homocysteine. When the body can't break down the homocysteine made from another amino acid methionine, it becomes toxic to the heart, brain, and bones. We are constantly eating methionine, a building block of protein, so a common treatment is eating a low-protein diet with medical foods and vitamin pills. This can be hard to follow due to bad tastes and missing out on foods a person enjoys, especially in children.
The goal of this study is to provide participants with a supplement containing creatine, another amino acid related to methionine and homocysteine, and learn if it lowers homocysteine production in healthy adult men. We would ultimately like to see if creatine supplements are a potential alternate treatment of Homocystinuria in this proof of concept study, before studying individuals with the condition.
Read more
Researchers in this study want to know:
- How does the bodies digestion of isotope methionine change in breath and urine when creatine is taken in healthy young adult men?
- How do levels of homocysteine, methionine and related metabolites change in the blood when creatine is taken by healthy young adult men?
Participants will:
- Complete two (2), 8-hour study days on-site.
- Eat a lower protein diet for one (1) week before the first study day, and eat a lower protein diet with creatine supplements for one (1) week before the second study day.
- During both study days eat special hourly meals of controlled amino acids and nutrients, along with a methionine isotope. (An isotope is a stable labelled amino acid that is colourless, odorless, tasteless, and safe for consumption. In the lab we can detect this isotope in breath and urine samples collected during the study day).
- Provide samples of breath, urine and blood. (Researchers will also take body measurements (height weight), and use non-invasive tests to measure body composition and energy needs).
Read the detailed description
Homocystinuria is a rare but potentially serious inherited condition due to cystathionine beta-synthase (CBS) deficiency which causes accumulation of homocysteine and its precursor methionine.
Our hypothesis is that high doses of orally supplemented creatine will lead to a reduction of endogenous production of homocysteine. Our hypothesis is based on the tight association of the metabolic pathways for creatine synthesis and the synthesis of S-adenosylhomocysteine (SAH) which is the immediate precursor of homocysteine. Suppression of endogenous creatine synthesis through provision of exogenous creatine will lead to reduced production of SAH and thus homocysteine.
Our objectives are:
- To test endogenous methionine turn over using stable isotope technique in response to creatine supplementation in healthy young adult men
- To test changes in blood levels of homocysteine, S-adenosylmethionine (SAM), SAH and methionine as well as creatine metabolites dependent on creatine supplementation
To test the endogenous methionine turn over in response to creatine supplementation we will use stable isotope techniques utilizing labelled carbon (13C), as 1-13C-Methionine. The tracer will be given along with protein shakes composed of specific amounts of protein (1g/kg/d) and its metabolic fate can be tracked by measuring 13C labelled carbon dioxide (CO2) in breath samples and 13C species in urine with mass spectrometer. Stable isotopes have been used previously and are currently being used for metabolic studies in healthy children and adults, including pregnancy. Our Lab has special experience with this technique and has used it for the study of other inborn errors of metabolism. For the measurement of plasma levels of homocysteine, methionine, SAM, SAH, creatine and its intermediates we will use mass spectrometry, employing well established methods in our lab.
We will perform a baseline study (without previous creatine supplementation and a treatment study (with previous creatine supplementation) in two separate study days. Participants will take a diet providing 1 gram of protein /kg/day for 7 days prior to the respective study. For the treatment, study participants will additionally take 20 grams of creatine per day for 7 days. On the study days probands will take hourly experimental meals containing the tracer methionine and breath samples and urine samples will be collected to determine 13C species coming from the ingested methionine. We will collect blood during the 6th hour of the study to determine methionine and creatine related metabolites.
- Conditions
- Homocystinuria
- Being tested
- Creatine, Dietary methionine tracer and protein intake
- Medical subject headings
- Homocystinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CreatineDietary supplement
For 7 days, participants will take a 20mg creatine supplement each day.
Dietary methionine tracer and protein intakeDietary supplement
On the study days participants will ingest 8 hourly meals of controlled amino acid intake, fortified with the necessary macronutrients. Each meal will provide one-twelfth of the participants' daily energy requirements as estimated by 1.5 x Resting Energy Expenditure (REE) and adequate protein at 1.0 g/kg/d, to maintain a metabolic steady state. The meals are in the form of a crystalline amino acid protein shake, and protein-free cookies.
| Study group | Role | What they receive |
|---|---|---|
| Baseline - no creatine supplementation | Experimental | Each participant will complete a baseline study day. For 7 days prior to the study day each participant will eat a controlled diet of 1g protein/kg body weight/day. Receives: Dietary Supplement: Dietary methionine tracer and protein intake |
| Treatment - Creatine Supplementation 20mg | Experimental | Each participant will complete a supplemented study day. For 7 days prior to the study day each participant will eat a controlled diet of 1g protein/kg body weight/day, and the provided 20mg creatine supplement. Receives: Dietary Supplement: Creatine; Dietary Supplement: Dietary methionine tracer and protein intake |
What is being measured
The primary outcome is the main question the study is designed to answer.
Carbon 13 Oxidation
Urine and breath samples will be collected to measure the rate of L-[1-13C]methionine oxidation
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2024
- Study start19 Aug 2024
- Primary completion3 Jul 2025
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HomocystinuriaStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rajavel Elango, PhD, University of British Columbia
- Investigators
- Rajavel Elango, PhD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06495567
- Sponsor's protocol ID
- H23-02515
- Status last verified
- Feb 2026
- First submitted
- 3 Jul 2024
- Last updated
- 12 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Creatine Supplementation for CBS-related Homocystinuria: A Proof-of-concept Study in Healthy Adults
- ClinicalTrials.gov ID
- NCT06495567
- Acronym / sponsor ID
- H23-02515
- Conditions
- Homocystinuria
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 19 Aug 2024 (actual)
- Primary completion
- 3 Jul 2025 (actual)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 10 Jul 2024 (actual)
- 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.
Homocystinuria is a rare and inherited metabolic disorder, people with this condition don't have an enzyme needed to break down an amino acid called homocysteine. When the body can't break down the homocysteine made from another amino acid methionine, it becomes toxic to the heart, brain, and bones. We are constantly eating methionine, a building block of protein, so a common treatment is eating a low-protein diet with medical foods and vitamin pills. This can be hard to follow due to bad tastes and missing out on foods a person enjoys, especially in children.
The goal of this study is to provide participants with a supplement containing creatine, another amino acid related to methionine and homocysteine, and learn if it lowers homocysteine production in healthy adult men. We would ultimately like to see if creatine supplements are a potential alternate treatment of Homocystinuria in this proof of concept study, before studying individuals with the condition.
Researchers in this study want to know:
- How does the bodies digestion of isotope methionine change in breath and urine when creatine is taken in healthy young adult men?
- How do levels of homocysteine, methionine and related metabolites change in the blood when creatine is taken by healthy young adult men?
Participants will:
- Complete two (2), 8-hour study days on-site.
- Eat a lower protein diet for one (1) week before the first study day, and eat a lower protein diet with creatine supplements for one (1) week before the second study day.
- During both study days eat special hourly meals of controlled amino acids and nutrients, along with a methionine isotope. (An isotope is a stable labelled amino acid that is colourless, odorless, tasteless, and safe for consumption. In the lab we can detect this isotope in breath and urine samples collected during the study day).
- Provide samples of breath, urine and blood. (Researchers will also take body measurements (height weight), and use non-invasive tests to measure body composition and energy needs).
Detailed description
Homocystinuria is a rare but potentially serious inherited condition due to cystathionine beta-synthase (CBS) deficiency which causes accumulation of homocysteine and its precursor methionine.
Our hypothesis is that high doses of orally supplemented creatine will lead to a reduction of endogenous production of homocysteine. Our hypothesis is based on the tight association of the metabolic pathways for creatine synthesis and the synthesis of S-adenosylhomocysteine (SAH) which is the immediate precursor of homocysteine. Suppression of endogenous creatine synthesis through provision of exogenous creatine will lead to reduced production of SAH and thus homocysteine.
Our objectives are:
- To test endogenous methionine turn over using stable isotope technique in response to creatine supplementation in healthy young adult men
- To test changes in blood levels of homocysteine, S-adenosylmethionine (SAM), SAH and methionine as well as creatine metabolites dependent on creatine supplementation
To test the endogenous methionine turn over in response to creatine supplementation we will use stable isotope techniques utilizing labelled carbon (13C), as 1-13C-Methionine. The tracer will be given along with protein shakes composed of specific amounts of protein (1g/kg/d) and its metabolic fate can be tracked by measuring 13C labelled carbon dioxide (CO2) in breath samples and 13C species in urine with mass spectrometer. Stable isotopes have been used previously and are currently being used for metabolic studies in healthy children and adults, including pregnancy. Our Lab has special experience with this technique and has used it for the study of other inborn errors of metabolism. For the measurement of plasma levels of homocysteine, methionine, SAM, SAH, creatine and its intermediates we will use mass spectrometry, employing well established methods in our lab.
We will perform a baseline study (without previous creatine supplementation and a treatment study (with previous creatine supplementation) in two separate study days. Participants will take a diet providing 1 gram of protein /kg/day for 7 days prior to the respective study. For the treatment, study participants will additionally take 20 grams of creatine per day for 7 days. On the study days probands will take hourly experimental meals containing the tracer methionine and breath samples and urine samples will be collected to determine 13C species coming from the ingested methionine. We will collect blood during the 6th hour of the study to determine methionine and creatine related metabolites.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baseline - no creatine supplementation | Experimental | Dietary Supplement: Dietary methionine tracer and protein intakeEach participant will complete a baseline study day. For 7 days prior to the study day each participant will eat a controlled diet of 1g protein/kg body weight/day. |
| Treatment - Creatine Supplementation 20mg | Experimental | Dietary Supplement: Creatine, Dietary Supplement: Dietary methionine tracer and protein intakeEach participant will complete a supplemented study day. For 7 days prior to the study day each participant will eat a controlled diet of 1g protein/kg body weight/day, and the provided 20mg creatine supplement. |
Who may qualify
- Ages
- 19 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Cis-male
- Men who are classified as normal body weight and BMI (18.5-25kg/m2)
- Free of any concurrent illness (cold, flu, vomiting etc.)
- Not be claustrophobic (we will place a clear hood, which can easily be removed, over your head for approximately 20 min to measure your energy expenditure)
- Not be enrolled in any other research studies (as this may affect our study results)
Key exclusion criteria (5 listed)
- Men not in good health or have a metabolic, neurological, genetic, or immune disorder, including diabetes, hypoglycemia, hypertension and current or past history of kidney disease
- Men who have food allergies/sensitivities/intolerances to egg, corn, diary etc.
- Men who have current or recent past history of ingesting creatine supplements
- Men who are smokers
- Men who are following a non-traditional dietary pattern (e.g. Keto diet, Atkins diet, paleo diet, intermittent fasting, strict vegan, calorie restricted diet etc.)
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 |
|---|---|---|
| CreatineFor 7 days, participants will take a 20mg creatine supplement each day. | Dietary supplement | Treatment - Creatine Supplementation 20mg |
| Dietary methionine tracer and protein intakeOn the study days participants will ingest 8 hourly meals of controlled amino acid intake, fortified with the necessary macronutrients. Each meal will provide one-twelfth of the participants' daily energy requirements as estimated by 1.5 x Resting Energy Expenditure (REE) and adequate protein at 1.0 g/kg/d, to maintain a metabolic steady state. The meals are in the form of a crystalline amino acid protein shake, and protein-free cookies. | Dietary supplement | Baseline - no creatine supplementation, Treatment - Creatine Supplementation 20mg |
Primary outcome
Carbon 13 Oxidation
Time frame: 8 hours
Urine and breath samples will be collected to measure the rate of L-[1-13C]methionine oxidation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Homocystinuria
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Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment
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RecruitingPhase 1/2
Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)
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Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
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A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE)
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RecruitingObservational study
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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.
Rajavel Elango, PhD principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Creatine and Dietary methionine tracer and protein intake in people with Homocystinuria, run by University of British Columbia at 1 site in Canada.
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 5 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 12 Feb 2026. 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 Canada. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Carbon 13 Oxidation (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Feb 2026; AzTrials last refreshed its copy on 26 Oct 2026.