PreeclampsiaNCT01328600
Marinobufagenin as a Target for DIGIBIND in Preeclampsia
An observational study of Preeclampsia, run by National Institute on Aging (NIA) at 3 sites in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Preeclampsia
- How many people
- 144 participants
- Where
- 3 sitesRussia
- Study dates
- 16 Aug 2006to 29 Jul 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
None listed.
Who cannot join
- Eclampsia, i.e., the occurrence of seizures not attributed to another cause during pregnancy
- Significant antecedent obstetrical problems that may interfere with study assessments or safe participation in the study
- Evidence of non-reassuring fetal well being
- Evidence of a lethal or life-threatening fetal anomaly
- Antecedent hypertension (hypertension secondary to preeclampsia, treated or untreated is allowed)
- Antecedent renal, hepatic, or autoimmune disease
Show all 10Show fewer
- Medical or psychiatric disorders which are unstable or which might interfere with study assessments or safe participation in the study
- Evidence on medical history/evaluation of use of or need for digitalis-like products currently or in the future
- Serum creatinine greater than or equal to 1.5 mg/dl
- Inability to understand and provide informed consent
Trial locations and contacts
3 sites in 1 country.
Russia3 sites
City Hospital No. 9
Saint Petersburg
Pushlon Hospital
Saint Petersburg
Veevolozhsk Hospital
Saint Petersburg
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Preeclampsia
- Keywords
- Placenta, Pregnancy, Hypertension, Supplementation, Antibody
- Medical subject headings
- Pre-Eclampsia, Hypertension
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2011 (estimated)
- Study start16 Aug 2006
- Study completion29 Jul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PreeclampsiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Other
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alexei Y Bagrov, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01328600
- Sponsor's protocol ID
- 999906259
- Other IDs
- 06-AG-N259
- Status last verified
- 29 Jul 2014
- First submitted
- 1 Apr 2011
- Last updated
- 9 Dec 2019
- Results posted
- No
Publications
Hamlyn JM, Ringel R, Schaeffer J, Levinson PD, Hamilton BP, Kowarski AA, Blaustein MP. A circulating inhibitor of (Na+ + K+)ATPase associated with essential hypertension. Nature. 1982 Dec 16;300(5893):650-2. doi: 10.1038/300650a0. No abstract available.
PubMed 6292738Graves SW, Williams GH. An endogenous ouabain-like factor associated with hypertensive pregnant women. J Clin Endocrinol Metab. 1984 Dec;59(6):1070-4. doi: 10.1210/jcem-59-6-1070.
PubMed 6092405Ludens JH, Clark MA, Kolbasa KP, Hamlyn JM. Digitalis-like factor and ouabain-like compound in plasma of volume-expanded dogs. J Cardiovasc Pharmacol. 1993;22 Suppl 2:S38-41. doi: 10.1097/00005344-199322002-00014.
PubMed 7508024
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Marinobufagenin as a Target for DIGIBIND in Preeclampsia
- ClinicalTrials.gov ID
- NCT01328600
- Acronym / sponsor ID
- 999906259
- Conditions
- Preeclampsia
- Keywords
- Placenta, Pregnancy, Hypertension, Supplementation, Antibody
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 16 Aug 2006
- Study completion
- 29 Jul 2014
- First posted
- 4 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Time perspective
- Other
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- Eclampsia, i.e., the occurrence of seizures not attributed to another cause during pregnancy
- Significant antecedent obstetrical problems that may interfere with study assessments or safe participation in the study
- Evidence of non-reassuring fetal well being
- Evidence of a lethal or life-threatening fetal anomaly
- Antecedent hypertension (hypertension secondary to preeclampsia, treated or untreated is allowed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
- Background: PubMed 6292738Hamlyn JM, Ringel R, Schaeffer J, Levinson PD, Hamilton BP, Kowarski AA, Blaustein MP. A circulating inhibitor of (Na+ + K+)ATPase associated with essential hypertension. Nature. 1982 Dec 16;300(5893):650-2. doi: 10.1038/300650a0. No abstract available.
- Background: PubMed 6092405Graves SW, Williams GH. An endogenous ouabain-like factor associated with hypertensive pregnant women. J Clin Endocrinol Metab. 1984 Dec;59(6):1070-4. doi: 10.1210/jcem-59-6-1070.
- Background: PubMed 7508024Ludens JH, Clark MA, Kolbasa KP, Hamlyn JM. Digitalis-like factor and ouabain-like compound in plasma of volume-expanded dogs. J Cardiovasc Pharmacol. 1993;22 Suppl 2:S38-41. doi: 10.1097/00005344-199322002-00014.
Related trials for Preeclampsia
Recruiting
Exercise to Improve Heart and Metabolic Health After Childbirth in Women at High Risk for Preeclampsia
Postpartum Exercise, Cardiometabolic Health
RecruitingObservational study
Molecular Study of the Maternal-fetal Interface in Preeclampsia.
Preeclampsia
Active, not recruitingObservational study
The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruitingPhase 2
Furosemide vs Placebo in Severe Preeclampsia Postpartum
Severe Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexei Y Bagrov, M.D. principal investigator
National Institute on Aging (NIA)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Preeclampsia, run by National Institute on Aging (NIA) at 3 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01328600, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.