HomocystinuriaPhase 1/2NCT01192828
Oxidative Stress Markers In Inherited Homocystinuria And The Impact Of Taurine
A Phase 1/2 study testing taurine in people with Homocystinuria, run by University of Colorado, Denver at 4 sites in United States.
Trial summary
Cystathionine beta-synthase deficiency is an inherited disease that results in elevation of a substance called homocysteine (Hcy) in blood and urine. Individuals with this disorder have a very high risk for developing blood clots and are at risk for developing eye and bone abnormalities. Read more about this study
- Who is it for?
- Ages 8 to 49 years
- Conditions the study is for
- Homocystinuria
- What is being tested?
- taurine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2010to Dec 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 8 to 49 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- A confirmed biochemical, molecular, or enzymatic diagnosis of classic homocystinuria due to cystathionine beta-synthase deficiency (OMIM 236200)
- And not fully responsive to therapy (eg, total homocysteine (tHcy) levels above 50 µmol/L on therapy including on B6 therapy)
- Be over 8 years old and less than 50 years. The first four patients will be adults (age 18-50 years)
- Be able and willing to provide informed consent
Who cannot join
- Pregnancy: Females who are pregnant or lactating will be excluded from the study as the influence of pregnancy on the markers is not known nor is the safety of taurine supplementation in pregnancy.
- Continued antioxidant intake:
- Individuals currently taking taurine, over the counter energy drinks containing taurine or other high dose antioxidants and unwilling to discontinue this for the study period (including a 2 week wash out period) will be excluded as such intake will likely impact laboratory results.
- Individuals taking Vitamin C as a prescribed treatment for their homocystinuria will be excluded as the antioxidant therapy may impact antioxidant and inflammation markers. (As Vitamin C is not standard of care for this disease we anticipate this to have minimal impact on recruitment.)
- Individuals currently taking platelet aggregation inhibitors such as salicylate on a self prescribed basis and unwilling to discontinue this for the study period (including a washout period of at least two weeks prior to the study) will be excluded as salicylate intake will impact platelet study results. Individuals taking salicylate (or other platelet aggregation inhibitors) prescribed as a therapy for their homocystinuria or other health issues will not be asked to stop the medication. They will participate in the study, but will be excluded only from the platelet studies.
- Medication interactions: Individuals unable or unwilling to abstain from use of cyclic guanosine monophosphate (cGMP) phosphodiesterase 5 inhibitors (such as Viagra) during the study period will be excluded from the nitroglycerin-induced flow-mediated dilatation studies in accordance with known labeling contraindications.
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- Inflammatory status:
- Individuals who have a significant chronic illness that has a marked inflammatory component will be excluded from the study as the illness will impact inflammatory markers.
- Patients with an acute illness, which may impact inflammatory biomarkers, will be postponed for study entry until the acute illness is resolved. Entry into the study at a later day will be offered.
- Recent cardiovascular event. Cardiovascular events (stroke, myocardial infarct, deep vein thrombosis, pulmonary embolus, thrombosis, or uncontrolled hypertension) may interfere with platelet function studies and with various mediators during the first months after the event. Patients who had such an event within the last 6 months will be excluded.
- Hypertriglyceridemia. Individuals with a triglyceride level above 300 mg/dl will be excluded from the study.
- Informed consent: Individuals who are unwilling or unable to consent, or in the case of minors who are unwilling or unable to assent will be excluded due to lack of ability to ensure informed consent.
- Study compliance and integrity: Individual who anticipate an inability to comply with study procedures and requirements will be excluded.
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Trial locations and contacts
4 sites in 1 country.
United States4 sites
Childrens Hospital Colorado
Aurora, Colorado, 80045
University of Colorado
Aurora, Colorado, 80045
Duke University
Durham, North Carolina, 27708
Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Cystathionine beta-synthase deficiency is an inherited disease that results in elevation of a substance called homocysteine (Hcy) in blood and urine. Individuals with this disorder have a very high risk for developing blood clots and are at risk for developing eye and bone abnormalities. Current treatments are generally difficult to follow and can fail. Development of additional therapies has been limited by lack of understanding of how the disease works.
The purpose of this study is to see if oxidative stress and inflammation are involved in the disease process and if short-term supplementation with taurine is an effective treatment.
Funding source: FDA.
Read the detailed description
Cystathionine beta-synthase deficient homocystinuria(CBSDH) is an inherited disease that results in elevation of a substance called homocysteine(Hcy)in blood and urine. Individuals with this disorder have a very high risk for developing blood clots that can cause a stroke or other life-threatening problems. In addition, these individuals have bone and joint tissue abnormalities.
Current treatment with an extremely strict diet and medication (betaine) is very difficult to follow, and often fails. Development of additional treatment strategies has been limited by a lack of knowledge and understanding of how this disease works. Hence, there is a need to better understand what causes the blood clots and the bone and joint tissue abnormalities.
New data suggest that oxidative stress and inflammation play a central role in animals with this disease. Limited data on humans with this disease support this as well. Further, data from animals with this disease suggests that taurine, a natural body substance and food product, which is low in these patients, mitigates this effect. This study is designed to follow-up on these data.
The purpose of the study is to increase our understanding of the disease process in this disorder, and to see in a pilot study if short-term supplementation with taurine is an effective intervention. The aims of the study are to:
- see if substances (markers) associated with oxidative stress and inflammation are increased in individuals with CBSDH
- see if the levels of these markers relate to the levels of homocysteine
- see if the levels of these markers decrease with short-term taurine supplementation
- see how bood vessels and platelets (small substances in the blood that help blood clot) work in individuals with CBSDH, if their ability to work is related to levels of markers of oxidative stress and inflammation, and if taurine supplementation improves how they work
- see if alterations of bone strength are related to levels of markers of inflammation.
The hypotheses to be investigated are as follows:
- Biomarkers of oxidative stress and inflammation are increased in individuals with CBSDH
- The degree of elevation of the biomarkers of oxidative stress and inflammation is relative to the degree of elevation of homocysteine, the main accumulating substance for this disease.
- Treatment with taurine mitigates the elevation of biomarkers of oxidative stress and inflammation.
- Endothelial function (blood vessel function) is abnormal in individuals with CBSDH even when receiving standard therapy and is improved with taurine supplementation.
- Chronic platelet aggregation, a variable finding in individuals with CBSDH, is mitigated with taurine supplementation.
- Decreased bone mineral density relates to the increase in inflammatory markers in CBSDH.
In addition, baseline pharmacokinetics (how much taurine is in the blood) of oral pharmacologic doses of taurine will be developed.
- Conditions
- Homocystinuria
- Being tested
- taurine
- Keywords
- cystathionine beta-synthase (CBS)
- Medical subject headings
- Homocystinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
taurineDrug
Also called Not Applicable. No other names.
Take Taurine for 4 1/2 days, two doses per day
| Study group | Role | What they receive |
|---|---|---|
| Taurine | Experimental | Treatment with Taurine Receives: Drug: taurine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Thiobarbituric Acid Reactive Substances (TBARS) in Individuals With Cystathionine Beta Synthase Deficient Homocystinuria (CBSDH) Pre and Post Taurine Treatment.
TBARS were measured in plasma via colorimetric absorbance. TBARS are a marker of oxidative stress. They are formed as a by-product of lipid (fat) oxidation. TBARS predominantly reflect the level of malondialdehyde (MDA) a substance that is formed from the breakdown of polyunsaturated fatty acids.
Measured: Baseline and after 4 days of therapy.
Difference in Tumor Necrosis Factor Alpha (TNF-alpha) in Individuals With CBSDH Pre and Post Taurine Treatment.
TNF-alpha was measured in plasma via Luminex high sensitivity assay. TNF-alpha is a signaling protein, or cytokine that promotes an inflammatory response.
Measured: Baseline and after 4 days of treatment.
Secondary outcomes (4)
Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH Pre and Post Taurine Treatment
Endothelial function was measured by doppler brachial artery flow-mediated dilation (FMD) studies.
Measured: Baseline and after 4.5 days of taurine treatment
Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH and Homocysteine Levels Greater Than 125 Micromole/L Pre and Post Taurine Treatment.
Endothelial function was measured by doppler brachial artery flow-mediated dilation (FMD) studies.
Measured: Baseline and after 4.5 days of therapy.
Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH and Pre Taurine Exposure FMD Values Less Than 10 mm Pre and Post Taurine Treatment.
Endothelial function was measured by doppler brachial artery flow-mediated dilation (FMD) studies.
Measured: Baseline and after 4.5 days of therapy.
Percent of Individuals With Decreased Bone Mineral Density.
Bone mineral density was assessed via whole body dual energy X-ray absorptiometry (DEXA) with bone density corrected for age. The absolute DEXA value was not used for analysis, rather values below 2 standard deviations of normal were taken as evidence of osteoporosis.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2010 (estimated)
- Study startJan 2010
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HomocystinuriaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Johan VanHove, MD PhD MBA, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01192828
- Sponsor's protocol ID
- 08-1376
- Other IDs
- FDR003907
- Status last verified
- Jun 2018
- First submitted
- 30 Aug 2010
- Last updated
- 9 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxidative Stress Markers In Inherited Homocystinuria And The Impact Of Taurine
- ClinicalTrials.gov ID
- NCT01192828
- Acronym / sponsor ID
- 08-1376
- Conditions
- Homocystinuria
- Keywords
- cystathionine beta-synthase (CBS)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Jan 2010 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 1 Sep 2010 (estimated)
- Results
- Posted 9 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cystathionine beta-synthase deficiency is an inherited disease that results in elevation of a substance called homocysteine (Hcy) in blood and urine. Individuals with this disorder have a very high risk for developing blood clots and are at risk for developing eye and bone abnormalities. Current treatments are generally difficult to follow and can fail. Development of additional therapies has been limited by lack of understanding of how the disease works.
The purpose of this study is to see if oxidative stress and inflammation are involved in the disease process and if short-term supplementation with taurine is an effective treatment.
Funding source: FDA.
Detailed description
Cystathionine beta-synthase deficient homocystinuria(CBSDH) is an inherited disease that results in elevation of a substance called homocysteine(Hcy)in blood and urine. Individuals with this disorder have a very high risk for developing blood clots that can cause a stroke or other life-threatening problems. In addition, these individuals have bone and joint tissue abnormalities.
Current treatment with an extremely strict diet and medication (betaine) is very difficult to follow, and often fails. Development of additional treatment strategies has been limited by a lack of knowledge and understanding of how this disease works. Hence, there is a need to better understand what causes the blood clots and the bone and joint tissue abnormalities.
New data suggest that oxidative stress and inflammation play a central role in animals with this disease. Limited data on humans with this disease support this as well. Further, data from animals with this disease suggests that taurine, a natural body substance and food product, which is low in these patients, mitigates this effect. This study is designed to follow-up on these data.
The purpose of the study is to increase our understanding of the disease process in this disorder, and to see in a pilot study if short-term supplementation with taurine is an effective intervention. The aims of the study are to:
- see if substances (markers) associated with oxidative stress and inflammation are increased in individuals with CBSDH
- see if the levels of these markers relate to the levels of homocysteine
- see if the levels of these markers decrease with short-term taurine supplementation
- see how bood vessels and platelets (small substances in the blood that help blood clot) work in individuals with CBSDH, if their ability to work is related to levels of markers of oxidative stress and inflammation, and if taurine supplementation improves how they work
- see if alterations of bone strength are related to levels of markers of inflammation.
The hypotheses to be investigated are as follows:
- Biomarkers of oxidative stress and inflammation are increased in individuals with CBSDH
- The degree of elevation of the biomarkers of oxidative stress and inflammation is relative to the degree of elevation of homocysteine, the main accumulating substance for this disease.
- Treatment with taurine mitigates the elevation of biomarkers of oxidative stress and inflammation.
- Endothelial function (blood vessel function) is abnormal in individuals with CBSDH even when receiving standard therapy and is improved with taurine supplementation.
- Chronic platelet aggregation, a variable finding in individuals with CBSDH, is mitigated with taurine supplementation.
- Decreased bone mineral density relates to the increase in inflammatory markers in CBSDH.
In addition, baseline pharmacokinetics (how much taurine is in the blood) of oral pharmacologic doses of taurine will be developed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Taurine | Experimental | Drug: taurineTreatment with Taurine |
Who may qualify
- Ages
- 8 to 49 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- A confirmed biochemical, molecular, or enzymatic diagnosis of classic homocystinuria due to cystathionine beta-synthase deficiency (OMIM 236200)
- And not fully responsive to therapy (eg, total homocysteine (tHcy) levels above 50 µmol/L on therapy including on B6 therapy)
- Be over 8 years old and less than 50 years. The first four patients will be adults (age 18-50 years)
- Be able and willing to provide informed consent
Key exclusion criteria (14 listed)
- Pregnancy: Females who are pregnant or lactating will be excluded from the study as the influence of pregnancy on the markers is not known nor is the safety of taurine supplementation in pregnancy.
- Continued antioxidant intake:
- Medication interactions: Individuals unable or unwilling to abstain from use of cyclic guanosine monophosphate (cGMP) phosphodiesterase 5 inhibitors (such as Viagra) during the study period will be excluded from the nitroglycerin-induced flow-mediated dilatation studies in accordance with known labeling contraindications.
- Inflammatory status:
- Recent cardiovascular event. Cardiovascular events (stroke, myocardial infarct, deep vein thrombosis, pulmonary embolus, thrombosis, or uncontrolled hypertension) may interfere with platelet function studies and with various mediators during the first months after the event. Patients who had such an event within the last 6 months will be excluded.
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 |
|---|---|---|
| taurineAlso: Not Applicable. No other names.Take Taurine for 4 1/2 days, two doses per day | Drug | Taurine |
Primary outcome
Difference in Thiobarbituric Acid Reactive Substances (TBARS) in Individuals With Cystathionine Beta Synthase Deficient Homocystinuria (CBSDH) Pre and Post Taurine Treatment.
Time frame: Baseline and after 4 days of therapy.
TBARS were measured in plasma via colorimetric absorbance. TBARS are a marker of oxidative stress. They are formed as a by-product of lipid (fat) oxidation. TBARS predominantly reflect the level of malondialdehyde (MDA) a substance that is formed from the breakdown of polyunsaturated fatty acids.
Difference in Tumor Necrosis Factor Alpha (TNF-alpha) in Individuals With CBSDH Pre and Post Taurine Treatment.
Time frame: Baseline and after 4 days of treatment.
TNF-alpha was measured in plasma via Luminex high sensitivity assay. TNF-alpha is a signaling protein, or cytokine that promotes an inflammatory response.
4 secondary outcomes
Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH Pre and Post Taurine Treatment
Time frame: Baseline and after 4.5 days of taurine treatment
Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH and Homocysteine Levels Greater Than 125 Micromole/L Pre and Post Taurine Treatment.
Time frame: Baseline and after 4.5 days of therapy.
Difference in Endothelial Function (Blood Vessel Function) in Individuals With CBSDH and Pre Taurine Exposure FMD Values Less Than 10 mm Pre and Post Taurine Treatment.
Time frame: Baseline and after 4.5 days of therapy.
Percent of Individuals With Decreased Bone Mineral Density.
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Johan VanHove, MD PhD MBA principal investigator
University of Colorado, Denver
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing taurine in people with Homocystinuria, run by University of Colorado, Denver at 4 sites 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 14 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 9 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Difference in Thiobarbituric Acid Reactive Substances (TBARS) in Individuals With Cystathionine Beta Synthase Deficient Homocystinuria (CBSDH) Pre and Post Taurine Treatment. (time frame: Baseline and after 4 days of therapy.). The study lists 2 primary outcomes in all. 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 9 Jul 2018.