Mechanisms That Produce the Leg Dysfunction of Claudication (Leg Pain and Limping During Walking) and Treatment Strategies for the Care of Patients With Claudication

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Nebraska
Sponsor:
Collaborators:
Information provided by (Responsible Party):
University of Nebraska
ClinicalTrials.gov Identifier:
NCT01970332
First received: September 4, 2013
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

Intermittent claudication afflicts 5% of the US population older than 55 years of age and develops along with hardening of the arteries of the legs. Claudicating patients limp and can only walk very short distances because their legs hurt. This protocol evaluates the mechanisms that may produce the leg dysfunction of claudication and its successful completion can ultimately produce significant new diagnostic and treatment strategies for the care of claudicating patients.


Condition Intervention
Peripheral Arterial Disease
Procedure: Revascularization Surgery
Other: Supervised exercise therapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: Mitochondrial Dysfunction, Oxidative Damage and Inflammation in Claudication

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Walking distances [ Time Frame: six months ] [ Designated as safety issue: No ]
    Initial Claudication Distance, Absolute Claudication Distance, 6-Minute Walking Distance

  • Quality of life [ Time Frame: six months ] [ Designated as safety issue: No ]
    Walking Impairment Questionnaire and the Medical Outcomes Study Short Form 36 Healthy Survey

  • Leg biomechanics [ Time Frame: six months ] [ Designated as safety issue: No ]
    Propulsion Impulse, Ankle plantarflexor torque, Ankle plantarflexor power and maximum isometric plantarflexion force

  • Leg hemodynamics [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Ankle Brachial Index


Secondary Outcome Measures:
  • Myofiber Mitochondrial Function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Mitochondrial Respiration measured via polarography

  • Myofiber Oxidative Damage [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Myofiber content of HNE adducts and protein carbonyls. Muscle Manganese Superoxide Dismutase activity

  • Muscle inflammation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Expression of pro- and anti-inflammatory cytokines and monocyte/macrophage cell counts.

  • Myofiber Morphology [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Cross-sectional area of the myofibers


Estimated Enrollment: 200
Study Start Date: September 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No Exercise Therapy or Revascularization operation
The patient is evaluated but no intervention
Experimental: Revascularization Surgery
The patient undergoes surgery to revascularize the ischemic, symptomatic limb(s)
Other: Supervised exercise therapy
Experimental: Exercise Therapy
The patient undergoes supervised exercise therapy for 6 months
Procedure: Revascularization Surgery

Detailed Description:

Claudication, defined as walking-induced leg discomfort and gait dysfunction relieved by rest, affects 5% of Americans over 55 years of age. Claudicating patients adopt sedentary lifestyles and cluster at the extreme low end of the physical activity spectrum, escalating risk for adverse health effects. The primary therapeutic goals for claudicating patients are restoration of leg function and prevention of disease progression. Current, rehabilitative interventions focus on inadequate blood flow as the only cause of claudication. Operative revascularization and/or exercise therapy are the principal conventional therapeutic modalities, providing only modest rehabilitative benefit. Applying biomechanical analysis to gait of claudicating patients, the investigators team has developed preliminary data indicating that blood flow is not the only mechanism producing the limb dysfunction of claudication. Several laboratories including the investigators own have demonstrated a myopathy, characterized by mitochondrial dysfunction, oxidative damage and inflammation, in leg skeletal muscle of claudicating patients. These conditions have not been quantified, comprehensively, in relation to claudication, and their association with severity of claudication is not known. The investigators hypothesis is that blood flow restriction is not a good predictor of limb dysfunction in claudication, whereas muscle mitochondrial dysfunction, oxidative damage and inflammation are strong predictors of limb dysfunction both at baseline and after conventional therapy with revascularization or supervised exercise. Under Aim #1, the investigators will acquire precise measurements of gastrocnemius mitochondrial function, oxidative damage and inflammation in claudicating patients, at the time of their initial presentation, and evaluate these measurements as predictors of objective measures of limb function and subjective measures of quality of life. Under Aims #2 and #3, the investigators will evaluate the effects of revascularization (Aim#2) and supervised exercise therapy (Aim#3) on mitochondrial dysfunction, oxidative damage and inflammation in claudicating gastrocnemius and on objective measures of limb function and subjective measures of quality of life. If the investigators hypothesis is correct, the work in Aim #2 will for the first time definitively demonstrate that blood flow restriction due to blockages in the arterial tree is not the only cause of claudication. The work under Aims #2 and #3 will determine whether revascularization or exercise therapy has a beneficial effect on the myopathy of claudicating muscle with associated improvement in limb function and quality of life. Finally, the proposed studies under Aims #1, #2 and #3 will provide quantitative modeling of a panel of mechanistic (bioenergetics, oxidative stress and inflammation) parameters as predictors of objective measurements of claudicating limb function and subjective measures of quality of life commonly used for clinical assessment. Measurements of gastrocnemius mitochondrial function, oxidative damage and inflammation may be useful tools that permit staging of disease for optimum intervention and evaluation of therapeutic interventions that specifically target these conditions, improving rehabilitative outcomes.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • a positive history of chronic claudication
  • exercise-limiting claudication established by history and direct observation during a screening walking test administered by the evaluating vascular surgeon
  • an ankle/brachial index < 0.90 at rest

Exclusion Criteria:

  • absence of Peripheral Arterial Disease (PAD)
  • acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
  • exercise capacity limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology
  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: NCT01970332

Locations
United States, Nebraska
Omaha VA Medical Center Recruiting
Omaha, Nebraska, United States, 68105
Contact: Holly K. DeSpiegelaere, RN, BSN, BA, CCRC    402-995-4171    Holly.DeSpiegelaere@va.gov   
Contact: Iraklis I Pipinos, MD, PhD    800-451-5796 ext 94171    ipipinos@unmc.edu   
Principal Investigator: Iraklis I Pipinos, MD, PhD         
Sponsors and Collaborators
University of Nebraska
  More Information

No publications provided

Responsible Party: University of Nebraska
ClinicalTrials.gov Identifier: NCT01970332     History of Changes
Other Study ID Numbers: 510-10, 5R01AG034995
Study First Received: September 4, 2013
Last Updated: October 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
Peripheral Arterial Disease
Peripheral Vascular Disease
Claudication
Myopathy
Oxidative stress
Mitochondrial dysfunction
Biomechanics
Inflammation

Additional relevant MeSH terms:
Inflammation
Peripheral Arterial Disease
Peripheral Vascular Diseases
Pathologic Processes
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 28, 2014