Marinobufagenin as a Target for DIGIBIND in Preeclampsia
Condition: Preeclampsia
MeSH terms: Pre-Eclampsia
Study type: Observational

Summary: 
      Background:

        -  Preeclampsia is a combination of high blood pressure and other potentially
           life-threatening symptoms. Preeclampsia occurs in up to 10% of pregnancies and is a main
           cause of maternal and fetal death worldwide. Treatment is often difficult, and so far
           there is no specific and effective therapy. Researchers have been studying the body
           systems that regulate blood pressure. They have also studied drugs that can control
           certain blood chemicals that constrict blood vessels and increase blood pressure.

        -  DIGIBIND, a drug that lowers blood pressure, has been used to treat pre-eclampsia.
           Marinobufagenin (MBG), a chemical in the blood that constricts blood vessels, has been
           shown to be involved in pre-eclampsia. But researchers are still not certain whether
           DIGIBIND can be used to specifically target MBG. Researchers want to find out whether
           DIGIBIND acts against MBG specifically. This information may help them to develop better
           drugs to block MBG and lower blood pressure in women with preeclampsia.

      Objectives:

      - To study whether the blood pressure treatment drug DIGIBIND specifically acts on
      marinobufagenin levels in the blood of pregnant women.

      Eligibility:

      - Women between 18 and 50 years of age who are 34 to 39 weeks pregnant and have preeclampsia.

      Design:

        -  Participants will be screened with a physical examination, medical history, and blood
           and urine tests.

        -  Before delivery, participants will provide blood samples for testing and evaluation.

        -  Following delivery, participants will provide additional blood samples and samples of
           the placenta for testing and evaluation.

        -  No additional treatment, apart from the standard of care, will be provided as part of
           this protocol.
    

Detailed description: 
      Preeclampsia (PE) complicates from 5 to 10% of pregnancies and it is a number one cause of
      maternal and fetal morbidity and mortality worldwide. Nevertheless, a specific and highly
      effective therapy of this disorder does not exist. As illustrated by therapeutic efficacy of
      anti-digoxin antibody (DIGIBIND) in preeclampsia, endogenous digitalis-like sodium pump
      ligands play an important role in the pathogenesis of this syndrome. Previously, we
      demonstrated that levels of endogenous bufadienolide Na/KATPase inhibitors are elevated in
      patients with PE, and that antibody to marinobufagenin lower blood pressure in rats with
      pregnancy-induced hypertension and ex vivo reverse inhibition of the Na/K-ATPase from
      erythrocytes from patients with PE. Most recently, we developed three anti-MBG monoclonal
      antibodies which in lower blood pressure in several rat experimental models.

      We are proposing a pilot proof-of concept study aimed to demonstrate that MBG is target for
      DIGIBIND in preeclampsia. If successful, this trial will provide basis for the development of
      a clinically-usable anti-MBG monoclonal antibody. We hypothesize that in patients with
      preeclampsia DIGIBIND induces vasorelaxation due to blockade of circulating MBG. The specific
      aims of the study are to demonstrate that isolated perfused preeclamptic placentae ex vivo
      release MBG at concentration sufficient to induce vasoconstriction that DIGIBIND reverses
      vasoconstriction induced by placental perfusate, and that vasorelaxant effect of DIGIBIND is
      due to blockade of MBG.

      The study population will be pregnant women (18-50 years), 34-39 weeks of fetal gestational
      age with preeclampsia The primary outcome of the study variable will be the difference in the
      vascular tone in isolated perfused cotyledons. The secondary outcomes will be: (i) the degree
      of MBG binding to DIGIBIND at different time points following DIGIBIND administration, (ii)
      the effect of DIGIBIND on the activity of Na/K-ATPase in erythrocytes, and (iii) the ex vivo
      effect of DIGIBIND on the vascular tone in the isolated placental lobes.
    

Time perspective: Other
Keywords: Placenta; Pregnancy; Hypertension; Supplementation; Antibody