Clinical trial NCT05373927: Calf Muscle Perfusion in Patients With Intermittent Claudication by Non-invasive MSOT
Official title: Cross-sectional Study of Calf Muscle Perfusion in Patients With Intermittent Claudication by Non-invasive Multispectral Optoacustic Tomography
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Peripheral Vascular Diseases
Peripheral Arterial Disease
Intermittent Claudication
Keywords: Peripheral Vascular Diseases
Peripheral Arterial Disease
Peripheral Artery Disease
PAD
Intermittent Claudication
Claudicatio intermittens
Critical Limb Ischaemia
CLI
Critical Limb Threatening Ischemia
CTLI
Color-Coded Duplex Sonography
CCDS
Ankle Brachial Index
ABI
Multispectral Optoacoustic Tomography
MSOT
Heel Raises
6-minute walk test
6MWT
Muscle Perfusion
Calf Muscle Perfusion
Lead sponsor: University Hospital Erlangen
Sponsor class: OTHER
Collaborators: name: PD Dr. med. Ferdinand Knieling, Department of pediatrics, University of Erlangen-Nürnberg
First posted: 2022-05-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with

* PAD IIa
* PAD IIb presenting for consultation during consultation hours of the department of vascular surgery.

Healthy volunteers being recruited by notices posted in the clinic with following conditions:

* no PAD previously known
* no diabetes mellitus previously known
* no chronic renal insufficiency previously known
* no symptoms of intermittent claudication
* ABI with values between 0.9 and 1.4 (screening examination before inclusion in the study)
* palpable foot pulses

Brief summary: The objective of the proposed study is to define independent parameters for the diagnostic assessment of the perfusion situation of the calf muscle based on multispectral optoacoustic tomography (MSOT) in a cross-sectional collective of patients with PAD in Fontaine stage II (intermittent claudication) and a healthy control collective (study group 1). The results will be validated using an independent validation group (study group 2).

Detailed description: PAD is one of the most common diseases of the elderly. As life expectancy increases, there is a growing need for new treatment concepts and new diagnostic procedures.

Up to now, only the measurement of macrocirculation in the form of CCDS, ABI and measurement of the actual walking distance are available as independent validation measures of revascularization methods (endovascular/open). The S3 guideline for diagnosis, therapy and medical aftercare of PAD published in 2015 by DGA (Deutsche Gesellschaft für Angiologie, German Society for Angiology) recommends such aftercare examinations, especially for patients that underwent vascular surgery. However, for the mentioned validation measures there are some patient groups for which these methods provide only insufficient or unusable results (e.g. diabetes mellitus, terminal renal failure). In these cases, independent verification of the success of the chosen therapy would have to be performed using angiography (digital subtraction angiography, CT angiography or MR angiography). However, this is not routinely performed in the respective patient populations due to the associated risks (including radiation exposure, contrast agent administration, invasiveness).

MSOT provides a new non-invasive diagnostic method that may be able to fill this diagnostic gap. A first study (MSOT_PAD, NCT04641091) confirmed the hypothesis that data collected via MSOT examination of the calf muscle can be used for PAD diagnostics. The derived concentration of oxygenated hemoglobin (HbO2) proved to be the most suitable measurement parameter. A connection could be established between the measured HbO2 concentration and the clinical stage of PAD. Differentiation improved after a standardized exercise of a walking distance of 150 meters, with patients in the stage of intermittent claudication (IC, Fontaine stage II) being more difficult to differentiate in comparison to patients in Fontaine stages III and IV.

The aim of this cross-sectional study is to increase the sensitivity and specificity of the procedure for IC patients by using a more suitable exercise between first and second MSOT measurement, namely repeated heel raises until the occurrence of claudication pain. A subgroup of the IC patients having been included in the study will be asked to undergo the study protocol a second time after interventional/ surgical revascularization. This is to investigate whether and how the improved blood flow situation translates to the measured MSOT parameters.

As additional target variables, the relative, absolute and total walking distance in a 6-minute walk test as well as the PAD-specific quality of life will be recorded with the VASCUQOL-6 questionnaire. A healthy control collective is included as a comparison group.

Eligibility criteria: Inclusion Criteria:

* Patients with manifest PAD in stage II according to Fontaine or categories 1-3 according to Rutherford or healthy volunteers
* Adults (\>18 years) who are able to give their consent

Exclusion Criteria:

* Patients with PAD stage I, III and IV according to Fontaine or categories 0, 4, 5 and 6 according to Rutherford or healthy volunteers with diabetes mellitus, chronic renal failure, claudication symptoms, abnormal ABI or non-palpable foot pulses
* Underage persons
* Lack of written consent
* Safety concerns of the study physician (person with physical, mental or psychiatric conditions which, by the judgement of the study physician, would compromise the person's safety or the quality of the data, thereby rendering the person an ineligible candidate for the study)

Primary outcomes:
measure: Optimal diagnostic MSOT thresholds
timeFrame: single time point (1 day)
Secondary outcomes:
measure: Difference between the corresponding MSOT values before and after exercise
timeFrame: single time point (1 day)
measure: Reperfusion profiles for hemoglobin-associated parameters
timeFrame: single time point (1 day)
measure: Correlation of acquired MSOT parameters with the CCDS flow profile and PSV
timeFrame: single time point (1 day)
measure: Correlation of acquired MSOT parameters with the ABI
timeFrame: single time point (1 day)
measure: Correlation of acquired MSOT parameters with relative and absolute walking distance
timeFrame: single time point (1 day)
measure: Correlation of acquired MSOT parameters with maximum walking distance within 6 minutes
timeFrame: single time point (1 day)
measure: Correlation of acquired MSOT parameters with the subjectively perceived maximum walking distance in everyday life
timeFrame: single time point (1 day)
measure: Correlation of acquired MSOT parameters with the perceived PAD-specific quality of life (VASCUQOL-6 questionnaire)
timeFrame: single time point (1 day)
measure: Correlation of the acquired MSOT parameters with the TASC-classification (angiography)
timeFrame: single time point (1 day)
measure: Subgroup analysis: Difference between the corresponding MSOT values before and after revascularization intervention
timeFrame: two time points (2 days)
measure: Subgroup analysis: Reperfusion profiles for hemoglobin-associated parameters after revascularization intervention
timeFrame: single time point (1 day)
measure: Subgroup analysis: Correlation of acquired MSOT parameters after intervention with the CCDS flow profiles and PSVs after intervention
timeFrame: single time point (1 day)
measure: Subgroup analysis: Correlation of acquired MSOT parameters after intervention with the ABI after intervention
timeFrame: single time point (1 day)
measure: Subgroup analysis: Correlation of acquired MSOT parameters after intervention with relative (until the first occurrence of pain) and absolute walking distance (until the first stopping due to pain) determined during the 6MWT after intervention
timeFrame: single time point (1 day)
measure: Subgroup analysis: Correlation of acquired MSOT parameters after intervention with maximum walking distance in the 6MWT after intervention
timeFrame: single time point (1 day)
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: University of Erlangen-Nuremberg (FAU), Department of Vascular Surgery
state: Bavaria
Study officials:
References:
citation: Lawall H, Diehm C, Hoffmann U, Reinecke H. [Update PAVK: Epidemiology, comorbidity and prognosis of peripheral arterial obstructive disease]. Dtsch Med Wochenschr. 2015 Dec;140(24):1798-802. doi: 10.1055/s-0041-107064. Epub 2015 Dec 1. German.
citation: Lawall H, Huppert P, Espinola-Klein C, Zemmrich CS, Ruemenapf G. German guideline on the diagnosis and treatment of peripheral artery disease - a comprehensive update 2016. Vasa. 2017 Mar;46(2):79-86. doi: 10.1024/0301-1526/a000603. Epub 2017 Jan 27.
citation: Alpert JS, Larsen OA, Lassen NA. Exercise and intermittent claudication. Blood flow in the calf muscle during walking studied by the xenon-133 clearance method. Circulation. 1969 Mar;39(3):353-9. doi: 10.1161/01.cir.39.3.353. No abstract available.
citation: Karlas A, Masthoff M, Kallmayer M, Helfen A, Bariotakis M, Fasoula NA, Schafers M, Seidensticker M, Eckstein HH, Ntziachristos V, Wildgruber M. Multispectral optoacoustic tomography of peripheral arterial disease based on muscle hemoglobin gradients-a pilot clinical study. Ann Transl Med. 2021 Jan;9(1):36. doi: 10.21037/atm-20-3321.
citation: Larsen ASF, Reiersen AT, Jacobsen MB, Klow NE, Nordanstig J, Morgan M, Wesche J. Validation of the Vascular quality of life questionnaire - 6 for clinical use in patients with lower limb peripheral arterial disease. Health Qual Life Outcomes. 2017 Sep 22;15(1):184. doi: 10.1186/s12955-017-0760-3.