Marinobufagenin as a Target for DIGIBIND in Preeclampsia
|First Received Date ICMJE||April 1, 2011|
|Last Updated Date||October 23, 2014|
|Start Date ICMJE||August 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01328600 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Marinobufagenin as a Target for DIGIBIND in Preeclampsia|
|Official Title ICMJE||Marinobufagenin as a Target for DIGIBIND in Preeclampsia|
- To study whether the blood pressure treatment drug DIGIBIND specifically acts on marinobufagenin levels in the blood of pregnant women.
- Women between 18 and 50 years of age who are 34 to 39 weeks pregnant and have preeclampsia.
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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||170|
|Estimated Completion Date||July 2014|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 50 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Russian Federation|
|Removed Location Countries|
|NCT Number ICMJE||NCT01328600|
|Other Study ID Numbers ICMJE||999906259, 06-AG-N259|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||National Institute on Aging (NIA)|
|Study Sponsor ICMJE||National Institute on Aging (NIA)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||July 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP