The Effects of Tiopronin on 3-Aminopropanal Level & Neurologic Outcomes after Subarachnoid Hemorrhage

Purpose of the Study

The purpose of this study is to determine the safety and appropriate dose of a drug, called tiopronin, which may help in patients who have had bleeding into their brain.

Up to 60 patients may be enrolled in this study at the Harborview Medical Center. Participants will be actively followed as a part of this study for 12 months. They are invited to participate in a research study of the treatment for the leakage of blood from a ruptured blood vessel around the brain: a condition called aneurysmal subarachnoid hemorrhage (aSAH). The treatment involves an experimental drug, called tiopronin.

Following an aSAH, approximately half of patients experience constriction of brain arteries (vasospasm), which causes poor blood supply to the brain. This can result in neurological deficits that can be even more devastating than the effects of the initial aSAH. Studies have shown that brain damage due to poor blood flow leads to the formation of a chemical called 3-aminopropanal (3AP), which is a molecule that is toxic to brain cells.

Patients with more severe aSAH have high levels of 3AP compared to patients with less severe aSAH. Animal and human studies have shown that compromised blood flow to the brain leads to elevated levels of 3AP. In addition, in further animal studies, it has been shown that the drug tiopronin can neutralize 3AP, and in animals that undergo experimental compromise of blood flow to the brain, those treated with tiopronin have a smaller area of brain damage compared to those who do not receive tiopronin.

Tiopronin is a medication that is approved by the US Food and Drug Administration (FDA) for another purpose. It is approved for use in patients at risk for one type of kidney stone. In addition, it is approved for other uses in Europe. Use of Tiopronin for this study is considered experimental. We have permission from the FDA to use this medication in this specific study of aSAH.

Because animal studies have shown that tiopronin reduces the size of brain damage (infarct size) and reduces the level of the neurotoxin 3AP, we aim to show in this study that tiopronin is safe in aSAH patients, that it actually gets into the fluid surrounding the brain (cerebrospinal fluid) after taking it by mouth, and that it reduces the levels of the neurotoxin 3AP.

Patients who have recently had an aneurysmal subarachnoid hemorrhage may qualify as possible participants in this study. It is anticipated that 60 patients will be enrolled in this trial.

For more information, or to participate in this study, please contact the Principal Investigator or Research Coordinators:

Principal Investigator:

Dr. Louis Kim
Assistant Professor
Department of Neurological Surgery
University of Washington
Phone: (206) 744-9302

Research Coordinator:

Alana Clark, BA
Department of Neurological Surgery
Phone: (206) 744-9364

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