Marinobufagenin as a Target for DIGIBIND in Hypertensive Patients With End-stage Renal Disease - Full Text View

Sponsor:	National Institute on Aging (NIA)
Collaborator:	University of Toledo Health Science Campus
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00852787

Purpose

The purpose of this study is to examine the effects of the digibind drug on hemodialysis patients with high blood pressure. Digibind is used to treat toxicity from digoxin and digoxin-like molecules which may contribute to high blood pressure.

Condition	Intervention	Phase
Hypertension Hemodialysis	Drug: Digoxin immune fab Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Marinobufagenin as a Target for DIGIBIND in Hypertensive Patients With End-stage Renal Disease

Resource links provided by NLM:

MedlinePlus related topics: Dialysis High Blood Pressure Kidney Failure

Drug Information available for: Digoxin

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:

Blood pressure [ Time Frame: Screening, and 24-hour period after first infusion and after second infusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Marinobufagenin levels [ Time Frame: Screening, and after first and second infusions ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	April 2009
Estimated Study Completion Date:	February 2011
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Low 0.1mg/kg	Drug: Digoxin immune fab Intravenously one time Other Name: Digibind
Experimental: Medium 0.4mg/kg	Drug: Digoxin immune fab Intravenously one time Other Name: Digibind
Experimental: High 1.6 mg/kg	Drug: Digoxin immune fab Intravenously one time Other Name: Digibind
Placebo Comparator: Placebo	Drug: Placebo Intravenously one time

Detailed Description:

High blood pressure is a very common problem in patients with kidney disease. Researchers have noted that there are certain molecules in the blood of these patients that may be contributing to the high blood pressure. In particular these molecules have been labeled as "digoxin-like substances." Digoxin is a drug made from a certain plant that may contribute to high blood pressure. In research animals with kidney failure, it has been noted that the use of Digibind helps to lower the blood pressure in these animals. Digibind is a drug made from sheep that is used to treat the toxicity from digoxin as well as toxicity from molecules similar to digoxin.

In this study, volunteers that are on hemodialysis and have high blood pressure will be given a placebo or the digibind drug intravenously on two separate visits. The volunteers will then wear a 24-hour blood pressure monitor and return the following day. Volunteers will receive the Digibind at one visit during the study, and the placebo on the other visit.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Aged 18-75 years of age
On hemodialysis with predialysis BP > 150/90 but ≤ 180/110
On at least one anti-hypertensive medication for 6 consecutive readings
Able to have blood pressure measured in an arm
Women of child bearing potential must not be pregnant; must use contraception during the study and for one month after the study
Receiving adequate dialysis (KT/V > 1.2)
Compliant with the dialysis schedule and duration

Exclusion Criteria:

Pregnant or nursing women
Arm blood pressure is not possible to obtain
Currently on digitalis
On any Digibind-type product in the past
History of allergies to antibiotics
History of asthma
Medical or psychiatric disorders which are unstable or which might interfere with study assessments or safe participation in the study
History of use of, or evidence of need for, digitalis-like products
Inability to understand or provide informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00852787

Contacts

Contact: Deepak Malhotra, MD, PhD

419-383-3705

Deepak.Malhotra@utoledo.edu

Locations

United States, Ohio
University of Toledo Medical Center	Recruiting
Toledo, Ohio, United States, 43614
Contact: Deepak Malhotra, MD, PhD 419-383-3705 Deepak.Malhotra@utoledo.edu
Principal Investigator: Deepak Malhotra, MD, PhD

Sponsors and Collaborators

National Institute on Aging (NIA)

University of Toledo Health Science Campus

Investigators

Principal Investigator:

Deepak Malhotra, MD, PhD

University of Toledo

More Information

Publications:

Bagrov AY, Shapiro JI. Endogenous digitalis: pathophysiologic roles and therapeutic applications. Nat Clin Pract Nephrol. 2008 Jul;4(7):378-92. Epub 2008 Jun 10. Review.

Mohmand B, Malhotra DK, Shapiro JI. Uremic cardiomyopathy: role of circulating digitalis like substances. Front Biosci. 2005 Sep 1;10:2036-44. Review.

Fedorova OV, Simbirtsev AS, Kolodkin NI, Kotov AY, Agalakova NI, Kashkin VA, Tapilskaya NI, Bzhelyansky A, Reznik VA, Frolova EV, Nikitina ER, Budny GV, Longo DL, Lakatta EG, Bagrov AY. Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension. J Hypertens. 2008 Dec;26(12):2414-25.

Responsible Party:	Deepak Malhotra, MD, PhD, University of Toledo
ClinicalTrials.gov Identifier:	NCT00852787 History of Changes
Other Study ID Numbers:	AG0115, 263-MA-707136-1
Study First Received:	February 26, 2009
Last Updated:	December 18, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

Digoxin like substances
digibind
digoxin immune fab
end-stage-renal-disease
marinobufagenin

Additional relevant MeSH terms:

Hypertension
Kidney Diseases
Kidney Failure, Chronic
Vascular Diseases
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Digoxin
Bufanolides
Marinobufagenin

Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Protective Agents
Physiological Effects of Drugs
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on February 09, 2012