Trial record 11 of 133 for:    Peripheral Arterial Disease OR claudication OR peripheral vascular disease | Open Studies | NIH, U.S. Fed

Zibotentan, an Endothelin Receptor Antagonist, Patients With Intermittent Claudication

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Virginia
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Brian Annex, MD, University of Virginia
ClinicalTrials.gov Identifier:
NCT01890135
First received: June 18, 2013
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

Peripheral artery disease (PAD) is a major complication of atherosclerosis when blockages in the arteries to leg reduce blood flow and one of the resulting problems is termed intermittent claudication (IC). IC is leg pain with walking that is relieved with rest and IC is the most frequent clinical manifestation of PAD and it effects millions of Americans. The number of patients with, and the health care costs of, PAD will increase as the prevalence of PAD is associated with advancing age, diabetes, and smoking. Zibotentan (ZD4054) is an endothelin receptor A (ETA) blocker that undergone extensive human testing and has been shown to be safe in several patient population. There is ample evidence to suggest that an ETA blocker could improve blood flow to the legs in patients with PAD. In a study that will be funded by the National Institute of Health, the investigators will test the ability of this medication to allow better blood flow to the legs of patients with PAD. In patients with IC, the investigators will test the ability of ZD4054 to improve leg blood flow using a non-invasive imaging technique. In parallel the study will test for the ability of patients with leg pain to walk further and feel better.


Condition Intervention Phase
Peripheral Arterial Disease
Intermittent Claudication
Drug: Zibotentan (ZD4054)
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Phase II Clinical Trail to Assess the Safety and Effects of ZD4054 (Zibotentan) on Exercise Induced Calf Muscle Perfusion in Patients With Intermittent Claudication (Rutherford II or III).

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Change in exercise-induced calf muscle perfusion by magnetic resonance imaging [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in peak walking time [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Peak walking time (PWT) will be measured using the Gardner treadmill protocol which is designed for patients with peripheral arterial disease.

  • Change in quality of life measures [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Quality of life measures specific to peripheral arterial disease will be assessed by questionnaire.

  • Safety [ Time Frame: Baseline and Day 30 ] [ Designated as safety issue: Yes ]
    Confirmation of lack of change in edema or heart failure by history and physical examination


Other Outcome Measures:
  • Change in ankle-brachial blood pressure index (ABI [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change in hematocrit [ Time Frame: baseline and day 30 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 44
Study Start Date: June 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: endothelin receptor antogonist
10 mg of zibotentan
Drug: Zibotentan (ZD4054)
10 mg
Drug: placebo
randomized double blind
Other Name: matched placebo
Placebo Comparator: placebo
matched placebo
Drug: Zibotentan (ZD4054)
10 mg
Drug: placebo
randomized double blind
Other Name: matched placebo

Detailed Description:

Peripheral artery disease (PAD) is a major complication of atherosclerosis that affects >8 million people in the United States alone. Intermittent claudication (IC), defined as leg pain with walking that is relieved with rest, is the most frequent clinical manifestation of PAD.

In a proposal that was just funded by the National Institute of Health (NIH) National Center for Advancing TRanslational Sciences (NCATS) the investigators pose to test the "reuse" of zibotentan (ZD4054, an Asta-Zeneca compound), an orally active, endothelin receptor A (ETA) antagonist in patients with IC. The study will seek to confirm the safety and tolerability of 10mg of ZD4054 in patients with intermittent claudication (Rutherford II or III) and, in parallel, establish the capacity of ZD4054 to change calf muscle perfusion, as assessed by contrast-enhanced magnetic resonance imaging, functional treadmill performance, and quality of life indicators.

The study will be a 1:1 randomized, double-blind, placebo-controlled trial of 44 subjects with intermittent claudication with randomization stratified based on the entry calf muscle perfusion. The investigators will use magnetic resonance imaging to quantify changes in blood flow to the ischemic limb from baseline to week 12 between those randomized to drug vs. placebo. Based on the prior experience and the known tolerability of ZD4054, the experience of the investigative team with a mechanistically appropriate end-point measure that is part of other NIH funded projects, the investigators will proceed directly to this Phase II trial. The primary endpoint of the study will be the change in absolute perfusion in the index calf muscle from baseline to follow-up, after 12 weeks on the 10 mg dose or placebo. Additional outcome measures will be: a) ability of patients with PAD to tolerate 10 mg dose of ZD4054 vs. placebo; b) freedom from unexpected serious adverse events; c) change in peak walking time from baseline to 12 weeks between 10 mg of ZD4054 and placebo groups; d) change in ankle-brachial blood pressure index (ABI) from baseline to 12 weeks between 10 mg of ZD4054 and placebo groups, and; d) change in quality of life measure between 10 mg of ZD4054 and placebo groups.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >40 years. Patients less than 40 years of age could well have a form or "thromboangitis obliterans" often called Berger's Disease and the investigators wish to enroll only subjects with atherosclerotic vascular disease.
  • Currently taking all standard medications that are part of the "good medical care" for patients with PAD including an anti-platlet agent, an angiotensin-converting enzyme inhibitors or receptor blockers, beta-blockers if indicated for ischemic heart disease, and cholesterol lowering therapy; unless documented contra-indications to these therapies exist. Those patients not on these therapies will be referred back with the suggestion that they be added and they can be re-approached for enrollment at a later date.
  • Exercise induced thigh, calf, buttock pain and absence of Rutherford Class IV, V, or VI.3
  • A resting ABI of <0.9 but >0.4 and the presence of both superficial femoral artery stenosis (70% or greater) disease and below the knee disease with a significant stenosis in at least one of the run-off vessels.
  • Absence of critical inflow (iliac or common femoral) disease. The profunda femoral artery is the major source of collateral blood vessels. The investigators initial approach will be to try and enroll as homogenous of a patient population as possible to allow us to focus on the primary endpoint of the study (the change in muscle perfusion to the ischemic limb over time).
  • Ability to undergo magnetic resonance imaging and provide informed written consent.

Exclusion Criteria:

  • Serious known concomitant disease with life expectancy of less than one year
  • Prior amputation or history of critical limb ischemia
  • Creatinine clearance (CrCl) >45 to permit safe administration of the gadolinium contrast agent.
  • Recent myocardial infarction, unstable angina, stroke or transient ischemic attack within 3 months.
  • American Heart Association Class III or IV congestive heart failure or known left ventricular ejection fraction less than 40%.
  • Known history of anemia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01890135

Contacts
Contact: Brian H Annex, M.D. 434-924-0853 annex@virginia.edu
Contact: Diantha McKeel, BA, LPN, CCRC 434-243-6091 dhm8d@virginia.edu

Locations
United States, Virginia
University Of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Brian H Annex, MD    434-982-0853    annex@virginia.edu   
Contact: Diantha McKeel, BA, LPN, CCRC    434-243-6091    dhm8d@virginia.edu   
Principal Investigator: Brian H Annex, MD         
Sub-Investigator: Aditya M Sharma, M.D.         
Sub-Investigator: Christopher M Kramer, M.D.         
Sub-Investigator: Gilbert R Upchurch, M.D.         
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Brian H Annex, MD University of Virginia
  More Information

No publications provided

Responsible Party: Brian Annex, MD, Professor of Medicine, Chief Division of Cardiovascular Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT01890135     History of Changes
Other Study ID Numbers: 1 UH3TR000959-01
Study First Received: June 18, 2013
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
randomized
double blind
blood flow
muscle perfusion
safety

Additional relevant MeSH terms:
Intermittent Claudication
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Signs and Symptoms
Atherosclerosis

ClinicalTrials.gov processed this record on July 22, 2014