Clinical trial NCT05111379: Acute Local Metabolomic Alterations in Blood and Muscle Tissue in Intermittent Claudication
Official title: Acute Local Metabolomic Alterations in Blood and Muscle Tissue in Intermittent Claudication
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of Tartu
Sponsor class: OTHER
Collaborators: name: Tartu University Hospital
name: Estonian Science Foundation
First posted: 2021-11-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with mild intermittent claudication (Fontaine IIa).

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;
* any revascularization within the preceding 3 month;
* marked heart failure (NYHA III-IV);
* blood pressure ≥ 180/110 mmHg;
* blood pressure \<100/70 mmHg;
* clinically significant heart valve disease;
* acute infectious disease;
* active malignancy or chemotherapy or disease-free \< 5 years;
* type I diabetes or insulin therapy;
* other clinically significant and untreated endocrine disorders;
* moderate to severe bronchial asthma (GINA 2016);
* severe chronic obstructive pulmonary disease (mMRC grade 3-4);
* acute (KDIGO 2012) or chronic renal disease (eGFR-EPI \<30mL/min/1.73 m2);
* acute or chronic liver disease;
* anemia (\<110 g/L);
* neuroinflammatory or neurodegenerative disease;
* active rheumatism;
* other diseases and factors that markedly hinder the subject's ability to walk during the treadmill exercise.
* For control group exclusively: history of lower extremity arterial disease / ABI \<1.0 or \>1.4.

Primary outcomes:
measure: Change in local metabolomic profile after treadmill exercise as reflected by arteriovenous gradients of low-molecular metabolites.
timeFrame: Blood sampling at two points in time: Baseline (Day 1) & 10-15 minutes after treadmill test (Day 2).
measure: 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).
timeFrame: Blood sampling at two points in time: Baseline (Day 1) & 10-15 minutes after treadmill test (Day 2).
Secondary outcomes:
measure: Change in local metabolomic profile after treadmill exercise as reflected by absolute concentrations of low-molecular metabolites in muscle biopsy.
timeFrame: Biopsy at two points in time: Baseline (Day 1) & 15-20 minutes after treadmill test (Day 2).
measure: Correlations between maximal walking distance and exercise-induced changes in local metabolomic and inflammatory profiles.
timeFrame: Data analysis after the enrollment period.
measure: Correlations between baseline arterial functionality/hemodynamic parameters and exercise-induced changes in local metabolomic and inflammatory profiles.
timeFrame: Data analysis after the enrollment period.
Other outcomes:
measure: Maximal walking distance on a treadmill (m).
timeFrame: During treadmill test (Day 2).
measure: Ankle-brachial index (no units).
timeFrame: Baseline (Day 1).
measure: Femoral artery intima-media thickness (mm).
timeFrame: Baseline (Day 1).
measure: Peripheral blood pressure, central blood pressure (mmHg).
timeFrame: Baseline (Day 1).
measure: Aortic pulse wave velocity (m/s).
timeFrame: Baseline (Day 1).
measure: Aortic augmentation index (%).
timeFrame: Baseline (Day 1).
measure: Identification of systemic metabolomic profile as reflected by absolute concentrations of low-molecular metabolites in peripheral blood sample.
timeFrame: Blood sampling at one point in time: Baseline (Day 1)
measure: Identification of systemic inflammatory profile as reflected by absolute concentrations of inflammatory mediators (IL-6, MPO, SOD, NOX isoform 1, NOX isoform 2, NOX isoform 5, nitrotyrosine, 8-iso-PGF2α) in peripheral blood sample.
timeFrame: Blood sampling at one point in time: Baseline (Day 1)
Locations:
city: Tartu
country: Estonia
facility: Tartu University Hospital
state: Tartumaa
Study officials:
affiliation: University of Tartu
name: Jaak Kals, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Tartu
name: Kaido Paapstel, MD, PhD
role: STUDY_CHAIR
affiliation: University of Tartu
name: Kalle Kilk, MD, PhD
role: STUDY_CHAIR
affiliation: University of Tartu
name: Holger Post, MD
role: STUDY_CHAIR
References: