Ignite Creation Date:
2024-07-17 @ 11:34 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06495567
Status:
RECRUITING
Last Update Posted:
2024-07-12
First Post:
2024-07-03
Brief Title:
Proof of Concept Creatine Supplementation for Homocystinuria Study
Sponsor:
University of British Columbia
Organization:
University of British Columbia
Study Overview
Official Title:
Creatine Supplementation for CBS-related Homocystinuria A Proof-of-concept Study in Healthy Adults
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Homocystinuria is a rare and inherited metabolic disorder people with this condition dont have an enzyme needed to break down an amino acid called homocysteine When the body cant 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
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
1 To test endogenous methionine turn over using stable isotope technique in response to creatine supplementation in healthy young adult men
2 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 1gkgd 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 kgday 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
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
1 To test endogenous methionine turn over using stable isotope technique in response to creatine supplementation in healthy young adult men
2 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 1gkgd 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 kgday 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None