Marinobufagenin as a Target for DIGIBIND in Hypertensive Patients With End-Stage Renal Disease

Condition(s) targeted: Hypertension; Hemodialysis

Intervention: Digoxin immune fab (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute on Aging (NIA)

Official(s) and/or principal investigator(s):
Deepak Malhotra, MD, PhD, Principal Investigator, Affiliation: University of Toledo

Overall contact:
Deepak Malhotra, MD, PhD, Phone: 419-383-3705, Email: Deepak.Malhotra@utoledo.edu

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.

Official title: Marinobufagenin as a Target for DIGIBIND in Hypertensive Patients With End-Stage Renal Disease

Study design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Crossover Assignment, Efficacy Study

Primary outcome: Blood pressure

Secondary outcome: Marinobufagenin levels

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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

Deepak Malhotra, MD, PhD, Phone: 419-383-3705, Email: Deepak.Malhotra@utoledo.edu

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

Related 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.

Starting date: April 2009
Ending date: February 2011
Last updated: May 6, 2009