Homocystinuria Clinical Trial
Official title:
Oxidative Stress Markers In Inherited Homocystinuria And The Impact Of Taurine
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.
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:
1. see if substances (markers) associated with oxidative stress and inflammation are
increased in individuals with CBSDH
2. see if the levels of these markers relate to the levels of homocysteine
3. see if the levels of these markers decrease with short-term taurine supplementation
4. 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
5. 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.
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