Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 61 of 92 for:    Recruiting, Not yet recruiting, Available Studies | "Cholesterol"

A Trial of Alirocumab and Plaque Regression in Peripheral Arterial Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02959047
Recruitment Status : Recruiting
First Posted : November 8, 2016
Last Update Posted : October 11, 2018
Sponsor:
Collaborator:
Northwestern University
Information provided by (Responsible Party):
Christopher Kramer, University of Virginia

Brief Summary:
Peripheral arterial disease (PAD) is characterized by lower limb arterial obstruction due to atherosclerosis. Magnetic resonance imaging (MRI) methods can accurately quantify atherosclerotic plaque in the superficial femoral artery (SFA) in patients with PAD. Such techniques have demonstrated plaque regression with statin therapy over 1 year. Alirocumab is a PCSK9 inhibitor that effectively reduces LDL cholesterol up to 70% in patients on statins or intolerant to statins. The investigators hypothesize that effective low density lipoprotein (LDL) lowering with Alirocumab 150m subcutaneously (SQ) every 2 weeks will regress atherosclerotic plaque in the SFA in patients with PAD over one year compared to placebo. 54 patients with mild-moderate PAD (ankle brachial index or ABI 0.4-0.9) will be randomized to alirocumab 150 mg SQ every 2 weeks or matching placebo at the University of Virginia (UVA) (n=34) and Northwestern (n=20). The primary endpoint is change in atherosclerotic plaque volume in the superficial femoral artery over the 1 year treatment period. Secondary endpoints include changes in peak calf muscle perfusion after thigh cuff occlusion/hyperemia, 6-minute walk distance, and blood biomarkers (LDL cholesterol, fibrinogen, high sensitivity c-reactive protein (hs-CRP), and lipoprotein(a).

Condition or disease Intervention/treatment Phase
Peripheral Arterial Disease Drug: Alirocumab Drug: Matching placebo Phase 4

Detailed Description:

PAD is characterized by lower limb arterial obstruction due to atherosclerosis. There are over 8.5 million people with PAD in the U.S. Recent data in a general population over 40 demonstrated an incidence of PAD defined by ankle brachial index (ABI) of 4.3%. Another study of over 3000 patients, mean age 59, demonstrated a prevalence of 3.9%. The prevalence is age-dependent, rising to 14.5% in those over 70. In populations at risk including diabetics or smokers, the incidence is nearly 30%. Standard cardiovascular (CV) risk factors are also risks for PAD, especially smoking, diabetes, hypertension, African-American race and chronic kidney disease. The annual rate of CV events including myocardial infarction, stroke, and CV death is 5-7%. The adjusted risk of dying of a CV event is 2-fold higher than those without PAD.

Magnetic resonance imaging (MRI) methods can accurately quantify atherosclerotic plaque in the superficial femoral artery (SFA) in patients with PAD. These measures can be performed rapidly and reproducibly with an intraclass correlation of 0.997 for intraobserver reproducibility, 0.987 for intraobserver, and 0.996 for test-retest reproducibility, Plaque regression with statins have been shown using these techniques in PAD.

Alirocumab is a PCSK9 inhibitor that effectively reduces LDL cholesterol up to 70% in patients on statins or intolerant to statins. This injectable agent has proven safe and well-tolerated, but has not yet been studied specifically in patients with peripheral arterial disease.The study will be a double blind, placebo-controlled, randomized study of Alirocumab vs. placebo in 54 patients with PAD.

Baseline visit: Informed consent will be signed. Vital signs will be taken and blood drawn fasting for baseline values. A MRI would be performed with black blood imaging of the SFA of both legs. Approximately 10-15 cm of each leg would be covered, using a specifically designed surface coil (Machnet, Leiden, NL). The imaging would start at the bifurcation of the common femoral and proceed distally. The pulse sequence used will be a black blood turbo spin echo proton density weighted sequence with 3mm slice thickness and 3mm gaps that will be subsequently interleaved. A single slice with an extensive amount of plaque will be chosen for imaging of plaque characteristics including T1- and T2-W imaging. Finally, a calf muscle perfusion study will be performed in the leg that is most symptomatic and/or has the lowest ABI in the absence of claudication symptoms. The calf will be wrapped in a flexible surface coil in a 3T scanner. Subjects will be placed supine in the MR scanner with the calf at the magnet isocenter. A thigh cuff will be inflated up to 250 mmHg for 5 min. Arterial spin labeling images of the mid-calf will be obtained immediately after release of the cuff.Regions of interest will be drawn on the relative blood flow maps corresponding to calf muscle groups to measure perfusion in ml/min/100g.

Randomization: The study statistician will do a block randomization and let the pharmacy know. Patients in the treatment group will begin treatment with alirocumab or matching placebo, 150 mg subcutaneously every 2 weeks. Treatment will continue for 26 treatments or 1 year.

Final Visit: This will be a repeat of the initial visit with vital signs, blood draw for lipid panel, and repeat MRI with the exact same protocol as on the initial visit.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomized Trial of Alirocumab and Plaque Regression in Peripheral Arterial Disease
Actual Study Start Date : July 17, 2017
Estimated Primary Completion Date : July 17, 2020
Estimated Study Completion Date : July 17, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab

Arm Intervention/treatment
Experimental: Alirocumab
Alirocumab 150mg SQ every 2 weeks
Drug: Alirocumab
150mg SQ every 2 weeks
Other Name: Praluent

Placebo Comparator: Placebo
Matched placebo
Drug: Matching placebo
SQ every 2 weeks




Primary Outcome Measures :
  1. Change in superficial femoral plaque volume (summed from both legs) [ Time Frame: 1 year ]
    Measured by black blood MRI, expressed in cm3


Secondary Outcome Measures :
  1. Change in calf muscle perfusion in the most symptomatic leg [ Time Frame: 1 year ]
    Measured by arterial spin labeling MRI, expressed in ml/min/100g

  2. Change in plaque characteristics [ Time Frame: 1 year ]
    % lipid in one slice from each leg

  3. Change in 6-minute walk test [ Time Frame: 1 year ]
    expressed in feet

  4. Change in LDL cholesterol [ Time Frame: 1 year ]
  5. Change in high sensitivity c-reactive protein [ Time Frame: 1 year ]
  6. Change in fibrinogen [ Time Frame: 1 year ]
  7. Change in lipoprotein (a) [ Time Frame: 1 year ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   35 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 35-85
  • Clinical diagnosis of peripheral arterial disease
  • Ankle brachial index of 0.4-0.9
  • Either on statin for at least 6 months or statin intolerant. The statin used should be a high potency statin (Crestor, Lipitor) or high dose of a lower potency statin (e.g. Zocor 40-80mg, Pravachol 40-80 mg)

Exclusion Criteria:

  • rest pain
  • critical limb ischemia
  • known or planned stent in the SFA
  • known occlusion of the SFA
  • planned revascularization within the next year
  • inability to lie flat
  • known contraindications to MRI including pacemaker, implantable cardioverter defibrillators, certain intracranial aneurysm clips, claustrophobia
  • pregnancy
  • known allergy to alirocumab

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02959047


Contacts
Layout table for location contacts
Contact: Christopher M Kramer, MD 4342430736 ckramer@virginia.edu
Contact: Jennifer R Kay, BSN 4342439937 jrh2g@virginia.edu

Locations
Layout table for location information
United States, Illinois
Northwestern University Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Mary McDermott, MD    312-503-6419    mdm608@northwestern.edu   
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Christopher M Kramer    434-243-0736    ckramer@virginia.edu   
Sponsors and Collaborators
University of Virginia
Northwestern University
Investigators
Layout table for investigator information
Principal Investigator: Christopher M Kramer, MD University of Virginia Health System

Layout table for additonal information
Responsible Party: Christopher Kramer, Professor, Department of Medicine, Cardiology, University of Virginia
ClinicalTrials.gov Identifier: NCT02959047     History of Changes
Other Study ID Numbers: 19404
First Posted: November 8, 2016    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Christopher Kramer, University of Virginia:
MRI
PCSK9 inhibition
LDL cholesterol
Additional relevant MeSH terms:
Layout table for MeSH terms
Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs