2 Clinical Trials for Various Conditions
Women with antibodies to proteins called SSA/Ro and or SSB/La face a 2% chance of having a child with a life threatening heart condition regardless of whether they have very active lupus, are in remission, or have only vague symptoms. This heart problem is referred to as congenital heart block (the most serious being third degree complete block) and represents damage thought to be caused by these autoantibodies. The heart beats abnormally slowly and almost all children require permanent pacemakers before the age of 20. Importantly, women who have had one child with heart block have a ten-fold higher risk of having another child with the same heart condition. Unfortunately, even close monitoring by special techniques during pregnancy does not reverse complete heart block once it is observed. Thus, treatments aimed at prevention are critical. This study will evaluate for the first time whether hydroxychloroquine, a drug used by many patients with SLE, prevents the development of this heart condition. Data from laboratory experiments suggests that this drug, which crosses the placenta, may decrease the inflammation initiated by the passage of anti-Ro antibodies to the fetus. The study uses a Simon's 2-Stage design, and plans to enroll 19 patients in Stage 1 and 35 patients in Stage 2 if Stage 1 is successful. Patients can already be on hydroxychloroquine or will be started as soon as pregnancy is confirmed. The hope is that fewer than 3 cases of heart block will occur in Stage 1, and fewer than 6 cases will occur out of all 54 patients if Stage 2 is reached. The results of this study are expected to become an integral part of the counseling of women with anti-Ro/La antibodies who are considering pregnancy.
Neonatal lupus (NL) is the name given to a group of conditions that can affect the babies of mothers who have certain autoantibodies against components of the body's cells that are called SSA/Ro and SSB/La. NL can appear as a temporary rash that usually goes away by the time the baby is 6 months old, or very rarely an abnormal blood or liver condition that also improves with time - or it can cause permanent and often life-threatening damage to the fetal heart, known as congenital heart block (CHB). In women with anti-Ro/La antibodies who are pregnant for the first time, only about 2% of the babies will develop CHB. But for a woman who has already had a child with CHB or NL rash, the risk of CHB in her next pregnancy is nearly 20%. Unfortunately, once complete (third degree) heart block has been unequivocally identified in a fetus, it has never been reversed with any of the therapies that have been tried to date. Our previous studies strongly indicate that scarring of the conduction system (the heart's own natural "pacemaker"), a consequence of inflammation triggered by the mother's antibodies, damages or even destroys the cells that allow the heart to beat at a normal rhythm. Instead, the damaged heart beats extremely slowly, to an extent that is fatal to nearly 20% of affected babies (with most deaths occurring as fetal demises). Nearly all surviving children with CHB require permanent implantation of a pacemaker device. Because it is so difficult to treat or repair the damaged heart, a high-priority strategy is to try to prevent the inflammatory process before irreversible scarring can occur. The aim of this clinical-based proposal is to determine whether treating the pregnant mother with intravenous immune globulin (IVIG) will prevent the development of CHB.