Acute Local Metabolomic Alterations in Blood and Muscle Tissue in Intermittent Claudication

NCT05111379 | Unknown

• 1 other identifier: 350/T-2
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The most common clinical presentation of lower extremity arterial disease is intermittent claudication. Current understanding of the pathophysiology of intermittent claudication, as well as its treatment options are limited. The progression of the disease may lead to lower limb amputation, which is devastating for patients' quality of life and is a huge socio-economic burden to society. Current study allows to determine the acute local metabolomic alterations in the ischaemic limb of the patient with intermittent claudication, and investigate the associations between the metabolomic alterations and the patient's maximal walking distance. This provides potentially valuable insight into the pathophysiology of this disease, and helps lay the groundwork for identifying potential novel targets for instituting more effective therapies for this high-risk population.

Conditions

Peripheral Arterial Occlusive Disease Fontaine Stage IIa

Keywords

lower extremity arterial disease; peripheral artery disease; intermittent claudication; local; metabolism; metabolomics; arteriovenous gradients; biomarkers; inflammation; ischemia-reperfusion injury

Outcome Measures

Primary Outcomes (2)

• Change in local metabolomic profile after treadmill exercise as reflected by arteriovenous gradients of low-molecular metabolites.

  Measured using liquid chromatography combined with mass spectrometry (AbsoluteIDQ MxP Quant 500 Kit, BIOCRATES Life Sciences AG, Austria).

  Blood sampling at two points in time: Baseline (Day 1) & 10-15 minutes after treadmill test (Day 2).

• Change in local inflammatory profile after treadmill exercise as reflected by arteriovenous gradients of inflammatory mediators (IL-6, MPO, SOD, NOX isoform 1, NOX isoform 2, NOX isoform 5, nitrotyrosine, 8-iso-PGF2α).

  Measured using enzyme linked immunosorbent assay. Measurement unit: ng/mL.

  Blood sampling at two points in time: Baseline (Day 1) & 10-15 minutes after treadmill test (Day 2).

Secondary Outcomes (3)

• Change in local metabolomic profile after treadmill exercise as reflected by absolute concentrations of low-molecular metabolites in muscle biopsy.

  Biopsy at two points in time: Baseline (Day 1) & 15-20 minutes after treadmill test (Day 2).

• Correlations between maximal walking distance and exercise-induced changes in local metabolomic and inflammatory profiles.

  Data analysis after the enrollment period.

• Correlations between baseline arterial functionality/hemodynamic parameters and exercise-induced changes in local metabolomic and inflammatory profiles.

  Data analysis after the enrollment period.

Other Outcomes (8)

• Maximal walking distance on a treadmill (m).

  During treadmill test (Day 2).

• Ankle-brachial index (no units).

  Baseline (Day 1).

• Femoral artery intima-media thickness (mm).

  Baseline (Day 1).

Study Arms (2)

LEAD (Fontaine IIa)

Patients with mild intermittent claudication.

Control

Healthy controls.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with mild intermittent claudication (Fontaine IIa).

You may qualify if:

• LEAD group: Patients with diagnosis of lower extremity arterial disease (Fontaine IIa).
• Control group: Healthy volunteers with no leg symptoms and an ankle-brachial index (ABI) of 1.0-1.4.

You may not qualify if:

• Fontaine stages I or IIb-IV
• Exacerbation of limb ischaemia within the preceding 2 weeks;
• strong rest pain of any cause;
• age \<18 or \>80 years;
• fasting \< 6 hours;
• time since last use of tobacco products \< 6 hours;
• body mass index ≥ 35 kg/m2
• poor sonographic visibility of femoral artery;
• angina;
• cardiac arrhythmia at the time of presentation;
• presence of cardiac pacemaker;
• myocardial infarction within the preceding 3 months;
• stroke within the preceding 6 months;
• ongoing anticoagulant therapy;
• ongoing dual antiplatelet therapy;

Sponsors & Collaborators

• University of Tartu: lead
• Tartu University Hospital: collaborator
• Estonian Science Foundation: collaborator

Study Sites (1)

Tartu University Hospital

Tartu, Tartu, 50406, Estonia

RECRUITING

Related Links

• Endothelial Research Centre

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, plasma, frozen tissue.

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication; Inflammation; Reperfusion Injury

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Postoperative Complications

Study Officials

• Jaak Kals, MD, PhD

  University of Tartu

  PRINCIPAL INVESTIGATOR

• Kaido Paapstel, MD, PhD

  University of Tartu

  STUDY CHAIR

• Kalle Kilk, MD, PhD

  University of Tartu

  STUDY CHAIR

• Holger Post, MD

  University of Tartu

  STUDY CHAIR

Central Study Contacts

Jaak Kals, MD, PhD

CONTACT

+372 731 8292; jaak.kals@kliinikum.ee

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: November 8, 2021
• Study Start: January 28, 2022
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2025
• Last Updated: May 25, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)