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Evaluation of trans sodium crocetinate on safety and exercise performance in patients with peripheral artery disease and intermittent claudication.

ABSTRACT: Trans sodium crocetinate (TSC) is a synthetic carotenoid that improves the diffusion of oxygen in animal models of ischemia/hypoxia. This study evaluated multiple doses of TSC in patients with peripheral artery disease (PAD) and hypothesized that a preliminary dose-response relationship could be identified on peak walking time (PWT). Forty-eight patients with symptomatic PAD and an ankle-brachial index < 0.90 were included, while critical limb ischemia, recent revascularization, and exercise limited by symptoms other than claudication were exclusionary. Patients were randomized to placebo or eight dosing levels of TSC ranging from 0.25 mg/kg to 2.0 mg/kg given intravenously once daily for 5 days. Subjects were tested on a graded treadmill protocol to claudication-limited PWT with the change to Day 5 as primary. A cubic regression was fit to detect a pre-specified inverted U-shaped dose-response relationship (65% power). Patient-reported walking distance from the Walking Impairment Questionnaire was a secondary endpoint. Adverse events were not predominant on any drug dose relative to placebo. Changes in PWT demonstrated a cubic trend for dose (p = 0.07, r = 0.39, r (2) = 0.15) with morphologic signals of benefit at doses above 1.00 mg/kg after both the first and fifth dosing days. Similar improvements occurred with the walking distance score at doses above 1.00 mg/kg. In conclusion, TSC was safe and well tolerated at all doses. Notable signals of benefit were observed at higher doses for both PWT and patient-perceived walking distance. These results support a phase II study to define the optimal dose for longer-term therapy with TSC. Clinical Trial Registration - URL:http://www.clinicaltrials.gov. Unique identifier: NCT00725881.

SUBMITTER: Mohler ER

PROVIDER: S-EPMC4182020 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Evaluation of trans sodium crocetinate on safety and exercise performance in patients with peripheral artery disease and intermittent claudication.

Mohler Emile R ER Gainer John L JL Whitten Kim K Eraso Luis H LH Thanaporn Porama Koy PK Bauer Timothy T

Vascular medicine (London, England) 20111001 5

Trans sodium crocetinate (TSC) is a synthetic carotenoid that improves the diffusion of oxygen in animal models of ischemia/hypoxia. This study evaluated multiple doses of TSC in patients with peripheral artery disease (PAD) and hypothesized that a preliminary dose-response relationship could be identified on peak walking time (PWT). Forty-eight patients with symptomatic PAD and an ankle-brachial index < 0.90 were included, while critical limb ischemia, recent revascularization, and exercise lim ...[more]

PMID: 22003000

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Project description:BackgroundAtherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms.MethodsAll participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety.ResultsA total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] -0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, -0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, -0.8 to 0.8; P=0.978), and capillary perfusion (-0.2±0.6%; 95% CI, -1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1-2.9; P=0.047) in participants with completely occluded femoral arteries.ConclusionsALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.

Project description:BackgroundLittle is known about the extent to which routine care management of peripheral arterial disease (PAD) and intermittent claudication (IC) align with best practice recommendations on exercise therapy. We conducted a scoping review to examine the published literature on the availability and workings of exercise therapy in the routine management of patients with PAD and IC, and the attitude and practice of health professionals and patients.MethodsA systematic search was conducted in February 2018. The Cumulative Index of Nursing and Allied Health Literature, Ovid MEDLINE, Allied and Complementary Medicine Database, ScienceDirect, Web of Science and the Directory of Open Access Repositories were searched. Hand searching of reference lists of identified studies was also performed. Inclusion criteria were based on study aim, and included studies that reported on the perceptions, practices, and workings of routine exercise programs for patients with IC, their availability, access, and perceived barriers.ResultsEight studies met the eligibility criteria and were included in the review. Studies conducted within Europe were included. Findings indicated that vascular surgeons in parts of Europe generally recognize supervised exercise therapy as a best practice treatment for IC, but do not often refer their patients for supervised exercise therapy due to the unavailability of, or lack of access to supervised exercise therapy programs. Available supervised exercise therapy programs do not implement best practice recommendations, and in the majority, patients only undergo one session per week. Some challenges were cited as the cause of the suboptimal program implementation. These included issues related to patients' engagement and adherence as well as resource constraints.ConclusionThere is a dearth of published research on exercise therapy in the routine management of PAD and IC. Available data from a few countries within Europe indicated that supervised exercise is underutilized despite health professionals recognizing the benefits. Research is needed to understand how to improve the availability, access, uptake, and adherence to the best exercise recommendations in the routine management of people with PAD and IC.

Project description:Background: The short-term benefits of aerobic and resistance exercise in subjects affected by Peripheral Arterial Disease (PAD) are scarcely examined in interaction. This study aimed to identify the effects of combined aerobic and resistance exercise programs on walking performance compared with isolated aerobic exercise or with the usual care in patients with intermittent claudication. Methods: A systematic review was conducted following the PRISMA statement. A total of five electronic databases were searched (until October 2019) for randomized and non-randomized controlled trials. The focus comprised PAD patients with intermittent claudication who performed a combined aerobic and resistance exercise program that assessed the walking performance. Results: Seven studies include combined aerobic and resistance exercise vs. isolated aerobic or vs. usual care. The studies represented a sample size of 337 participants. The follow-up ranged from 4 to 12 weeks, 2 to 5 times-per-week. The risk of bias in the trials was a deemed moderate-to-high risk. After the interventions, the percent change in walking performance outcomes had a large variation. In the combined and isolated aerobic programs, the walking performance always improved, while in the usual care group oscillates between the deterioration and the improvement in all outcomes. Combined exercise and isolated aerobic exercise improved the claudication onset distance from 11 to 396%, and 30 to 422%, the absolute claudication distance from 81 to 197%, and 53 to 121%, and the maximal walking distance around 23 and 10%, respectively. Conclusions: Currently, there is insufficient evidence about the effects of combined aerobic and resistance exercise compared to isolated aerobic exercise or usual care on walking performance. However, despite the low quality of evidence, the combined aerobic and resistance exercise seems to be an effective strategy to improve walking performance in patients with intermittent claudication. These combined exercise modes or isolated aerobic exercise produce positive and significant results on walking performance. The usual care approach has a trend to deteriorate the walking performance. Thus, given the scarcity of data, new randomized controlled trial studies that include assessments of cardiovascular risk factors are urgently required to better determine the effect of this exercise combination.

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Evaluation of trans sodium crocetinate on safety and exercise performance in patients with peripheral artery disease and intermittent claudication.

Publications

Evaluation of trans sodium crocetinate on safety and exercise performance in patients with peripheral artery disease and intermittent claudication.

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