The Impact of Diabetes on REvascularization (TIDE)

July 4, 2024 updated by: Joshua Beckman, Vanderbilt University Medical Center
The presence of foot symptoms at rest or tissue necrosis in patients with peripheral artery disease is a medical urgency and represents a state of critical limb ischemia (CLI) where the risk of amputation, in the absence of revascularization, is high. No trial conducted to date in peripheral revascularization has determined the effect of diabetes on mechanism of revascularization failure. Therefore, this trial represents a unique opportunity to investigate the mechanisms by which diabetes affects surgical and endovascular revascularization procedures with the long-term goal of improving outcomes in CLI.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Peripheral artery disease is a condition defined by marked accumulation of atherosclerotic plaque below the distal aorta that reduces lower limb arterial perfusion. Blood flow reductions may be inadequate for exercising limbs and cause ischemic muscle pain, called intermitted claudication, or, in severe cases, the reduction may be inadequate for basal metabolism and cause pain at rest, ulceration, or gangrene. The presence of symptoms at rest or tissue necrosis is a medical urgency and represents a state of critical limb ischemia (CLI) where the risk of amputation, in the absence of revascularization, is high. The ageing of the population and the increasing prevalence of diabetes mellitus ensures this population will continue to grow in the foreseeable future. The impact of diabetes, however, is not limited to PAD incidence. Diabetic patients represent a particularly vulnerable subset of PAD patients and have a four-fold risk of CLI compared to non-diabetic patients. Indeed, in previous studies of CLI, more than half of patients have diabetes. As a result, the combination of diabetes and PAD accounts for more than half of non-traumatic amputations in the United States. Diabetic patients often present with foot ulcerations as their first manifestation of PAD and have challenging anatomy for revascularization. Failed vascular reconstructions, both endovascular or surgical, often result in additional tissue loss and transtibial amputations. Despite these challenges, the mechanisms of restenosis and the impact of diabetes have not been well explored for both types of revascularization in patients with CLI. The BEST-CLI trial is a multi-center, randomized, comparative effectiveness trial comparing open surgical bypass therapy to endovascular therapy in CLI patients with a composite clinical endpoint denoted as Major Adverse Limb Event free survival (MALE-free survival). However, the BEST-CLI trial does not study the mechanisms by which revascularization may fail. This proposal will extend the novel clinical work of the BEST-CLI trial by studying the mechanisms of bypass vein graft and stent failure. The investigators will adjudicate the mode of revascularization (vein graft or stent) in a central core laboratory, measure systemic markers of diabetic dysmetabolism including inflammation, insulin resistance, adverse adipokine expression, poor nutrition, and renal dysfunction, and begin to study the association of these factors with graft failure. Indeed, no trial conducted to date in either coronary or peripheral revascularization has determined the mechanism of revascularization failure, the impact of diabetes, nor the relationship between conduit patency and clinical outcomes. Therefore, this trial represents a unique opportunity to investigate the mechanisms by which diabetes affects surgical and endovascular revascularization procedures.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
215

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
        • St. Boniface General Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1Y 4E9
        • The Ottawa Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences
    • Quebec
      • Québec, Quebec, Canada, G1L 3P7
        • Chu de Quebec, St-Francois d'Assise Hospital
  • Finland
      • Helsinki, Finland, 00029
        • Helsinki University Hospital
  • United States
    • California
      • Long Beach, California, United States, 90822
        • Long Beach VA Medical Center
      • Los Angeles, California, United States, 90033
        • Keck Medical Center of USC
      • San Francisco, California, United States, 94143
        • University Of California San Francisco Medical Center
      • San Francisco, California, United States, 94121
        • San Francisco VA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
    • Illinois
      • Chicago, Illinois, United States, 60153
        • Loyola University Medical Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
    • Iowa
      • West Des Moines, Iowa, United States, 50266
        • Iowa Heart Center
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • University Health System: LSU Health Sciences
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Medical School
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Flint, Michigan, United States, 48507
        • Michigan Vascular Center
      • Ypsilanti, Michigan, United States, 48197
        • Michigan Heart - St. Joseph Mercy Health System
    • Nebraska
      • Omaha, Nebraska, United States, 68106
        • University of Nebraska Medical Center
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New Jersey
      • Browns Mills, New Jersey, United States, 08015
        • Deborah Heart and Lung Center
      • Newark, New Jersey, United States, 07103
        • Rutgers University Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • New Mexico Heart Institute
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
      • Valhalla, New York, United States, 10595
        • Westchester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina Hospitals
      • Winston-Salem, North Carolina, United States, 28157
        • Wake Forest Baptist Health
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
      • Toledo, Ohio, United States, 43604
        • University of Toledo Medical Center
    • Oregon
      • Portland, Oregon, United States, 97204
        • Oregon Health and Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Memorial Hospital
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Heart and Vascular Institute
    • Washington
      • Seattle, Washington, United States, 98104
        • Harborview Medical Center
      • Seattle, Washington, United States, 98122
        • Benaroya Research Institute at Virginia Mason
    • Wisconsin
      • La Crosse, Wisconsin, United States, 54601
        • Gunderson Health System
      • Madison, Wisconsin, United States, 53706
        • University of Wisconsin - Madison

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This ancillary study is an observational study design examining the effects of diabetes mellitus on restenosis following surgical or endovascular revascularization in CLI patients. Eligible patients will be screened according to the specified exclusion and inclusion criteria of the BEST-CLI trial.

Description

Inclusion Criteria:

  • Male or female, age 35 years or older
  • Atherosclerotic, infrainguinal PAD
  • CLI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or rest pain, consistent with Rutherford classes 4-6
  • Candidate for either open or endovascular infrainguinal revascularization as judged by the treating investigators
  • Adequate inflow into the index femoral artery
  • Adequate popliteal, tibial, or pedal revascularization target
  • Willing to comply with protocol, attend follow-up appointments, complete all study assessments, and provide informed consent
  • Endovascular revascularization with a stent
  • Surgical revascularization with a vein graft-

Exclusion Criteria:

  • Femoropopliteal disease pattern consistent with TASC IIA
  • Complete occlusion of the iliac artery
  • Aortoiliac occlusive disease or severe common femoral artery disease
  • Presence of a femoral, popliteal or tibial aneurysm of the index limb
  • Life expectancy less than 2 years
  • Deemed excessive risk for surgical bypass
  • A vascular disease prognosis that includes an anticipated above ankle amputation on index limb within 4 weeks of index procedure
  • Renal dysfunction defined as MDRD eGFR ≤ 30ml/min/173 m2 at the time of screening
  • Currently on dialysis or history of a renal transplant
  • A documented hypercoagulable state
  • Nonatherosclerotic occlusive disease
  • Any prior infrainguinal revascularization
  • Current immuno-suppressive medication, chemotherapy or radiation therapy
  • Absolute contraindication to iodinated contrast

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Surgical Bypass
Subjects in the BEST-CLI trial assigned to surgical revascularization.
Diagnostic test: Platelet function testing
The investigators will test platelet reactivity at the beginning and midpoint of the first year after revascularization
Diagnostic test: Vascular ultrasonography
The investigators will test bypass graft and stent patency at 30 days, 6 months, and 1 year.
Endovascular
Subjects in the BEST-CLI trial assigned to endovascular revascularization.
Diagnostic test: Platelet function testing
The investigators will test platelet reactivity at the beginning and midpoint of the first year after revascularization
Diagnostic test: Vascular ultrasonography
The investigators will test bypass graft and stent patency at 30 days, 6 months, and 1 year.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Major Adverse Limb Event - free survival
Time Frame: 1 year
The combination of amputation, surgical revascularization, thrombectomy, thrombosis, interposition graft, or death
1 year
Restenosis
Time Frame: 1 year
Greater than 50% stenosis as determined by peak systolic velocity ratio of >2.4
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vanderbilt University Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Massachusetts General Hospital
Carelon Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 14, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 161402

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The proposed research will include data from approximately 500 subjects enrolled in the BEST-CLI clinical trial. The final dataset will include self-reported demographic, ultrasonographic, and laboratory data from the subjects. The investigators will be collecting identifying information, but the final dataset will be stripped of identifiers prior to release for sharing. Thus, the investigators will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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