Near-Infrared SpectroscopyNCT05229250
NIRS and Exercise Intensity in Patients With FLIA
An observational study of Near-Infrared Spectroscopy and Iliac Artery Stenosis, run by Maxima Medical Center at 1 site in Netherlands.
Trial summary
The research objectives of this project are to increase the understanding of pathophysiology and performance limitations related to sport-related flow limitation in the iliac artery (FLIA) using non-invasive measurement of muscle oxygenation at the working muscles of the leg and mechanical power output recorded during… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Near-Infrared Spectroscopy, Iliac Artery Stenosis, Iliac Artery Disease
- What is being tested?
- Cycling test, Occlusion tests and NIRS during cycling
- Type of treatment
- Medical device
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- 24 Aug 2022to 1 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Patients will be recruited after the diagnosis of FLIA is given during weekly standard clinical care. Healthy subjects will be recruited from local cycling clubs. They completed a standardized questionnaire excluding presence of risk factors such as smoking and positive cardiovascular family history. Candidates with FLIA were excluded. Candidates who fulfilled all study criteria, served as the control group
Who may be able to join
- Aged ≥ 18 years and ≤ 40 years
- Trained cyclist or triathlete regularly training at least ~3/week for at least five years and identifying with a particular cycle-sport
Who cannot join
- Earlier vascular iliac surgery
- Microvascular abnormalities (e.g. diabetes),
- Vascular abnormalities outside of the iliac region,
- Heart failure (New York Heart Association class >I),
- Orthopedic/neurological entities potentially limiting exercise capacity,
- Obesity.
Show all 9Show fewer
- Adipose tissue thickness > 7.5 mm
- These excluding conditions are considered as medical safety precautions to maximal exercise or as risk of unexpected pathophysiological effects confounding our primary outcome measures.
- It is known that a high level of adipose tissue thickness (ATT) influences the accuracy of NIRS measurement of underlying muscular tissue. A > 7.5 mm ATT cut-off point at the site of NIRS measurement determined with a skinfold caliper (Harpenden, Baty International West Sussex, UK) was chosen. The ATT is calculated as half the skinfold thickness.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Non-invasive Exercise Test for Evaluating Sport-related Arterial Blood Flow Limitation in the Leg: an Exploratory Study (NIRS and Cycling Power in Patients With FLIA)
The research objectives of this project are to increase the understanding of pathophysiology and performance limitations related to sport-related flow limitation in the iliac artery (FLIA) using non-invasive measurement of muscle oxygenation at the working muscles of the leg and mechanical power output recorded during cycling exercise. Skeletal muscle oxygenation measured with Near-Infrared Spectroscopy (NIRS) is growing more accessible for use by coaches, teams, and individual athletes for use in performance testing. Describing how muscle oxygenation profiles in endurance athletes diagnosed with FLIA differ in comparison with healthy athletes may allow the use of this non-invasive, accessible measurement device for the screening of athletes at risk of developing FLIA.
The relevance of this work is that FLIA imposes risk of irreversible injury to the main artery of the leg in endurance athletes, limiting their ability to participate in exercise, with further consequences for health, fitness, and quality of life. Currently, the early course of this progressive condition is poorly understood, as early detection is difficult and hence appropriate treatment is often delayed. If impairment becomes severe, often more invasive (and risky) treatment is necessary. Earlier detection and monitoring of FLIA may allow for improved patient management and outcomes.
The design of this experiment will compare a patient group of trained cyclists diagnosed with FLIA, to healthy control subjects including cyclists of a similar fitness level without signs of FLIA. Both groups will perform an incremental ramp cycling test and an intermittent multi-stage cycling exercise test. Incremental ramp cycling testing is used as part of clinical diagnosis of FLIA, as well as performance (eg. VO2max) testing of healthy athletes. Multi-stage exercise protocols are also often used for performance testing of endurance athletes and allows for observation of (path)physiological responses during submaximal work stages. Outcome measures of muscle oxygenation kinetics with NIRS and cycling power will be analysed and compared between patients and healthy subjects.
Read the detailed description
A professional cyclist covers approximately 25,000 km a year and flexes the hip 8,000,000 times in a year, while leg blood flow is in the range of 10-15 litres per minute. This poses a substantial hemodynamic load on the iliac artery. As a result, a proportion of endurance athletes develop a limitation in leg circulation due to arterial narrowing in this iliac artery. An early 'Lancet' study of the department of Sports Medicine of Máxima Medical Centre (MMC) found that 20% of professional cyclists were suffering from such a sport-related Flow Limitation in the Iliac Artery (FLIA) necessitating treatment. The incidence in recreational cyclists is unknown, but with 849,000 recreational cyclists in the Netherlands cycling over 3,000 km a year with an impressive 1,000,000 hip flexions, many of them travel similar distances as a professional cyclist, incurring similar risks for developing FLIA. If untreated, FLIA may have a pronounced impact on quality of life. Professional athletes may have to end their careers prematurely. In a substantial subset of cyclists, abnormalities may even lead to complete occlusion and/or thrombosis, with severe symptoms in daily life.
Clinical experience suggests that early detection and treatment leads to better outcomes. If diagnosed at a late stage, conservative management including changes in training behaviours and body position, or least-invasive surgical repair options will no longer suffice. The only options remaining would be to cease participation in the provocative activities altogether, or to undergo extensive and risky reconstructive vascular surgery. Understanding the early pathogenesis in order to improve detection is thus of paramount importance. Unfortunately, early detection is often missed due to the non-specific presentation of symptoms and the high level of specialisation required for clinical evaluation. There is a wide range of differential diagnoses that could contribute to the non-specific symptoms observed in the early stages of FLIA, including common musculoskeletal and tendinous injuries, mechanical or neurogenic pain referred from the low back or SI joint, hip acetabular labral tear, chronic exertional compartment syndrome, or fibromuscular dysplasia.8 Currently available diagnostic evaluations can have low sensitivity for an athletic population.
There is no single gold-standard evaluation for diagnosing FLIA. The current consensus suggests that the best single functional test is a provocative maximal exercise test on a cycle ergometer, followed by measuring blood pressure at the ankle and brachial arteries (ankle-brachial blood pressure index; ABI) in a competitive posture. In the rare case that the problem is unilateral, the sensitivity is 73%. If the problem is bilateral, the sensitivity is only 43%. Imaging techniques, including echo-Doppler examination, magnetic resonance angiogram (MRA), and computed tomography (CT) scan are more sensitive, but they are more expensive, less accessible, and not part of primary care evaluation, instead being typically reserved for investigation of more severe or complex presentations, and to guide surgical repair.
Near-infrared Spectroscopy (NIRS) is an innovative technique that measures relative oxygenation in the muscle, as the balance of oxygenated and deoxygenated haemoglobin and myoglobin. Impaired arterial leg circulation, such as observed in peripheral vascular disease (PVD) has been shown to produce a drop in oxygen saturation of skeletal muscle tissue relative to workload or exercise performance, and delays in reoxygenation kinetics after exercise and ischemic vascular occlusion tests (VOT). Consequently, NIRS may be able to detect alterations in oxygenation that are associated with the level of arterial insufficiency. We recently reported proof of concept studies regarding the potential diagnostic role of both power output and NIRS in patients with diagnosed sport-related FLIA.
Complaints reported in the early stages of FLIA are powerlessness and pain in the leg muscles when cycling near maximal exertion, which rapidly disappear with rest. Traditionally, incremental ramp cycling exercise to maximal exercise tolerance has been used as a provocative functional test, after which clinical outcome measures including ABI are tested. As the condition progresses however, symptoms can occur earlier during exercise at a lower intensity and take longer to resolve during recovery. Multi-stage exercise protocols are commonly used to understand metabolic responses related to submaximal exercise intensity. Therefore, a progressive multi-stage cycling protocol with brief recovery intervals between work intervals will be introduced. This protocol is designed to allow for multiple opportunities to evaluate work and recovery responses in an intensity-dependent manner. Subjective symptoms, performance impairments (including limitations to cycling power output) and muscle oxygenation kinetic delays will be evaluated across submaximal workloads including after maximal intensity.
Understanding the onset of symptoms and objective signs of flow limitation with progressive exercise intensity will improve understanding of severity and progression of this condition. These outcome measures will be compared to healthy subjects, in order to develop normative values related to healthy performance, compared to pathological impairment. The use of a common multi-stage performance assessment protocol will improve the applicability of using this approach for screening and early detection of FLIA outside of a specialised vascular clinic.
It has been suggested that altered vascular function and structure may contribute to the appearance of symptoms in patients in which obvious stenosis or intraluminal disease is not apparent on imaging. In addition to standard clinical evaluation of the aortoiliac tract with echo-Doppler ultrasound, vascular flow velocity will be recorded for later offline analysis of pulse wave velocity as a measurement of arterial stiffness.
- Conditions
- Near-Infrared Spectroscopy, Iliac Artery Stenosis, Iliac Artery Disease, Iliac Artery Occlusion
- Being tested
- Cycling test, Occlusion tests, NIRS during cycling, CPET, Echo-Doppler examination
- Keywords
- FLIA, NIRS, Endofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cycling testOther
RAMP and MULTI-STAGE test
Occlusion testsOther
Occlusion test before and after exercise
NIRS during cyclingDevice
NIRS devices measuring oxygenation during exercise
CPETDevice
Cardiopulmonary exercise testing (heart rate, pulmonary gas exchange) during exercise
Echo-Doppler examinationDevice
Peak systolic velocity and vascular stiffness measurements in the iliac-aortic tract
| Study group | Role | What they receive |
|---|---|---|
| Healthy subjects | Subjects without FLIA Receives: Other: Cycling test; Other: Occlusion tests; Device: NIRS during cycling; Device: CPET; Device: Echo-Doppler examination | |
| Patient subjects | Subjects with FLIA Receives: Other: Cycling test; Other: Occlusion tests; Device: NIRS during cycling; Device: CPET; Device: Echo-Doppler examination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Power-deoxygenation (PD) profile
Power-deoxygenation (PD) profile: The ratio of power output to deoxygenation (eg. power/deoxy[heme]) as a proxy for the metabolic disturbance at the working muscle relative to the workload.
Measured: During cyclingtest day 1
Near Infrared Spectroscopy (NIRS) deoxygenation parameters
Baseline: Average 60-second value before the start of exercise. min: the minimum 5-second mean value attained during exercise. max: the maximum 5-second mean value attained typically during the recovery after exercise.
Δexercise amplitude: the difference between baseline and minimum values.
Measured: During cyclingtest day 1
Near Infrared Spectroscopy (NIRS) deoxygenation parameters
Baseline: Average 60-second value before the start of exercise. min: the minimum 5-second mean value attained during exercise. max: the maximum 5-second mean value attained typically during the recovery after exercise.
Δexercise amplitude: the difference between baseline and minimum values.
Measured: During cyclingtest day 2
NIRS delta_recovery amplitude
The difference between minimum and maximum value.
Measured: During cyclingtest day 1
NIRS delta_recovery amplitude
The difference between minimum and maximum value.
Measured: During cyclingtest day 2
NIRS reoxygenation kinetics: tau
Time constant (tau, in seconds): the time constant parameter of a monoexponential curve fit to the reoxygenation profile after each work stage.
Measured: Immediately after exercise day 1
NIRS reoxygenation kinetics: Time delay
Time delay (TD, in seconds): the delay before systematic rise in oxygenation after each work stage.
Measured: Immediately after exercise day 1
NIRS reoxygenation kinetics: Mean Response Time
Mean response time (MRT, in seconds): the sum of TD and tau.
Measured: Immediately after exercise day 1
NIRS reoxygenation kinetics: Half value time
Half value recovery time (HVT, in seconds): the time required to reoxygenate half of the total amplitude during recovery after each work stage.
Measured: Immediately after exercise day 1
NIRS reoxygenation kinetics: Peak reoxygenation rate
Peak reoxygenation rate (SmO2/sec): a linear estimation of the peak resaturation slope, representing the magnitude of greatest mismatch between oxygen supply and utilization at the tissue during recovery kinetics, after each work stage.
Measured: Immediately after exercise day 1
NIRS reoxygenation kinetics: Peak reoxygenation MRT
Peak reoxygenation MRT: an estimate of the time to occurrence of the peak reoxygenation rate, analogous to the MRT in a monoexponential curve, and representing the balance of recovery kinetics of oxygen supply and utilization in the tissue after each work stage.
Measured: Immediately after exercise day 1
NIRS reoxygenation kinetics: tau
Time constant (tau, in seconds): the time constant parameter of a monoexponential curve fit to the reoxygenation profile after each work stage.
Measured: Immediately after exercise day 2
NIRS reoxygenation kinetics: Time delay
Time delay (TD, in seconds): the delay before systematic rise in oxygenation after each work stage.
Measured: Immediately after exercise day 2
NIRS reoxygenation kinetics: Mean response time
Mean response time (MRT, in seconds): the sum of TD and tau.
Measured: Immediately after exercise day 2
NIRS reoxygenation kinetics: Half Value time
Half value recovery time (HVT, in seconds): the time required to reoxygenate half of the total amplitude during recovery after each work stage.
Measured: Immediately after exercise day 2
NIRS reoxygenation kinetics: Peak reoxygenation rate
Peak reoxygenation rate (SmO2/sec): a linear estimation of the peak resaturation slope, representing the magnitude of greatest mismatch between oxygen supply and utilization at the tissue during recovery kinetics, after each work stage.
Measured: Immediately after exercise day 2
NIRS reoxygenation kinetics: Peak reoxygenation MRT
Peak reoxygenation MRT: an estimate of the time to occurrence of the peak reoxygenation rate, analogous to the MRT in a monoexponential curve, and representing the balance of recovery kinetics of oxygen supply and utilization in the tissue after each work stage.
Measured: Immediately after exercise day 2
Secondary outcomes (12)
Recovery kinetics VO2/NIRS comparison
To describe skeletal muscle oxygenation kinetics vs pulmonary oxygen uptake kinetics in both healthy cyclists and patients with FLIA
Measured: After stages/maximal exercise. This is an offline analyses and therefore takes the time of the stage (1 minute for in between blocks; 5 minutes for maximal exercise)
Vascular Occlusion Test - Reactive Hyperemia Area Under The Curve
Reactive Hyperemia area under the curve: the area of the NIRS signal (eg. SmO2⋅sec) will be calculated during the recovery from occlusion, as the total area under the curve and above the baseline value before cuff inflation during the first 4-minutes of recovery.
(This will be calculated from the same VOT for Outcome 1
Measured: Before cycling test day 1
Multiple reoxygenation kinetics - Primary Component Time constant tau
Primary component time constant (tau): the time constant parameter of a monoexponential curve fit to the rise in VO2 at the start of each work stage.
Measured: Between intervention day 1 (1-minute stages of block-protocol) and immediately after the intervention day 2 (ramp maximal test)
Multiple reoxygenation kinetics - Cardiodynamic component time delay
Cardiodynamic component time delay (TD): the delay before systematic rise in VO2 at the start of each work stage.
Measured: Between intervention day 1 (1 minustages of block-protocol) and immediately after the intervention day 2 (ramp maximal test)
Multiple reoxygenation kinetics - Δdeoxy[heme] / ΔVO2 onset kinetics
Δdeoxy[heme] / ΔVO2 onset kinetics: The oxygenation and VO2 curves will be normalized at the start of each work stage to a starting baseline and the eventual steady-state, as 0-100% of the response profile. The relative overshoot of Δdeoxy[heme] vs ΔVO2 can then be used to describe the matching of perfusive O2 delivery to O2 extraction.
Measured: During intervention day 1 (stages of block-protocol)
Multiple reoxygenation kinetics - Δdeoxy[heme] / ΔVO2 recovery kinetics
Δdeoxy[heme] / ΔVO2 recovery kinetics: The same comparison of the response profiles of deoxy[heme] and VO2 will be performed during recovery after work stages.
Measured: Between intervention day 1 (stages of block-protocol) and immediately after the intervention day 2 (ramp maximal test)
Vascular Occlusion Test (VOT): Microvascular Responsiveness
Microvascular Responsiveness (peak reoxygenation rate, eg. SmO2/sec): the linear slope of reoxygenation when the occlusion cuff is removed will be taken as the rate of reperfusion, representing microvascular responsiveness, a proxy for vasodilatory capacity and vascular function.
Measured: Before and after cycling test day 1
Vascular Occlusion Test (VOT): Reactive Hyperemia
Reactive Hyperemia area under the curve: the area of the NIRS signal (eg. SmO2⋅sec) will be calculated during the recovery from occlusion, as the total area under the curve and above the baseline value before cuff inflation during the first 4-minutes of recovery.
Calculated from same in VOT (Outcome 7)
Measured: Before and after cycling test day 1
Clinical Assessment
Peak systolic velocity (PSV): Measurement of PSV at the external iliac artery with echo-Doppler ultrasound, before and after exercise, and with and without provocative maneuvers can be discriminative for FLIA.
Measured: During the same examination-appointment. The PSV will be measured following measurments of the arterial stiffness. This takes about 10 minutes for both sides.
Clinical Assessment
Ankle brachial index (ABI): Blood pressures will be taken at bilateral ankles and from the arm both before and after exercise. The ratio of ankle and brachial pressures adjusted for height, and a bilateral difference can be discriminative for FLIA.
Measured: Immediately after maximal exercise day 1
Clinical Assessment
Ankle brachial index (ABI): Blood pressures will be taken at bilateral ankles and from the arm both before and after exercise. The ratio of ankle and brachial pressures adjusted for height, and a bilateral difference can be discriminative for FLIA.
Measured: Immediately after maximal exercise day 2
Clinical Assessment
Arterial stiffness with echo-Doppler: Arterial pulse wave velocities will be measured at the carotid and external iliac/femoral arteries with echo-Doppler ultrasound, before and after exercise. The velocity of propagation of the pulse wave is taken as an index of arterial stiffness.
Measured: Before exercise day 1, the arterial stiffness will be measured by the vascular technician. While this will be analyzed offline, this takes a few minutes.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2022
- Study start24 Aug 2022
- Primary completion1 May 2023
- Study completion1 Dec 2023
Why it stopped: The hardware failed multiple times. As such we chose to terminate teh study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Near-Infrared SpectroscopyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maxima Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Martijn van Hooff, Maxima Medical Center
- Investigators
- M van Hooff, MSc, Principal investigator, Maxima Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05229250
- Sponsor's protocol ID
- NL79767.015.21
- Status last verified
- Jan 2026
- First submitted
- 19 Nov 2021
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
van Hooff M, Schep G, Bender M, Scheltinga M, Savelberg H. Sport-related femoral artery occlusion detected by near-infrared spectroscopy and pedal power measurements: a case report. Phys Sportsmed. 2021 May;49(2):241-244. doi: 10.1080/00913847.2020.1796182. Epub 2020 Jul 26.
PubMed 32713244van Hooff M, Schep G, Meijer E, Bender M, Savelberg H. Near-Infrared Spectroscopy Is Promising to Detect Iliac Artery Flow Limitations in Athletes: A Pilot Study. J Sports Med (Hindawi Publ Corp). 2018 Dec 20;2018:8965858. doi: 10.1155/2018/8965858. eCollection 2018.
PubMed 30671480Schep G, Bender MH, van de Tempel G, Wijn PF, de Vries WR, Eikelboom BC. Detection and treatment of claudication due to functional iliac obstruction in top endurance athletes: a prospective study. Lancet. 2002 Feb 9;359(9305):466-73. doi: 10.1016/s0140-6736(02)07675-4.
PubMed 11853791Bender MH, Schep G, de Vries WR, Hoogeveen AR, Wijn PF. Sports-related flow limitations in the iliac arteries in endurance athletes: aetiology, diagnosis, treatment and future developments. Sports Med. 2004;34(7):427-42. doi: 10.2165/00007256-200434070-00002.
PubMed 15233596Peach G, Schep G, Palfreeman R, Beard JD, Thompson MM, Hinchliffe RJ. Endofibrosis and kinking of the iliac arteries in athletes: a systematic review. Eur J Vasc Endovasc Surg. 2012 Feb;43(2):208-17. doi: 10.1016/j.ejvs.2011.11.019. Epub 2011 Dec 19.
PubMed 22186674Hinchliffe RJ. Iliac Artery Endofibrosis. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):1-2. doi: 10.1016/j.ejvs.2016.04.006. Epub 2016 May 6. No abstract available.
PubMed 27161328INSITE Collaborators (INternational Study group for Identification and Treatment of Endofibrosis). Diagnosis and Management of Iliac Artery Endofibrosis: Results of a Delphi Consensus Study. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):90-8. doi: 10.1016/j.ejvs.2016.04.004. Epub 2016 May 17.
PubMed 27209899Khan A, Al-Dawoud M, Salaman R, Al-Khaffaf H. Management of Endurance Athletes with Flow Limitation in the Iliac Arteries: A Case Series. EJVES Short Rep. 2018 Jul 20;40:7-11. doi: 10.1016/j.ejvssr.2018.06.001. eCollection 2018.
PubMed 30101198Peake LK, D'Abate F, Farrah J, Morgan M, Hinchliffe RJ. The Investigation and Management of Iliac Artery Endofibrosis: Lessons Learned from a Case Series. Eur J Vasc Endovasc Surg. 2018 Apr;55(4):577-583. doi: 10.1016/j.ejvs.2018.01.018. Epub 2018 Mar 13.
PubMed 29548540Schep G, Bender MH, Schmikli SL, Mosterd WL, Hammacher ER, Scheltinga M, Wijn PF. Recognising vascular causes of leg complaints in endurance athletes. Part 2: the value of patient history, physical examination, cycling exercise test and echo-Doppler examination. Int J Sports Med. 2002 Jul;23(5):322-8. doi: 10.1055/s-2002-33142.
PubMed 12165882Barstow TJ. Understanding near infrared spectroscopy and its application to skeletal muscle research. J Appl Physiol (1985). 2019 May 1;126(5):1360-1376. doi: 10.1152/japplphysiol.00166.2018. Epub 2019 Mar 7.
PubMed 30844336Perrey S, Ferrari M. Muscle Oximetry in Sports Science: A Systematic Review. Sports Med. 2018 Mar;48(3):597-616. doi: 10.1007/s40279-017-0820-1.
PubMed 29177977Boezeman RP, Moll FL, Unlu C, de Vries JP. Systematic review of clinical applications of monitoring muscle tissue oxygenation with near-infrared spectroscopy in vascular disease. Microvasc Res. 2016 Mar;104:11-22. doi: 10.1016/j.mvr.2015.11.004. Epub 2015 Nov 11.
PubMed 26576829Cornelis N, Chatzinikolaou P, Buys R, Fourneau I, Claes J, Cornelissen V. The Use of Near Infrared Spectroscopy to Evaluate the Effect of Exercise on Peripheral Muscle Oxygenation in Patients with Lower Extremity Artery Disease: A Systematic Review. Eur J Vasc Endovasc Surg. 2021 May;61(5):837-847. doi: 10.1016/j.ejvs.2021.02.008. Epub 2021 Mar 30.
PubMed 33810977Kleinloog JPD, van Hooff M, Savelberg HHCM, Meijer EJ, Schep G. Pedal power measurement as a diagnostic tool for functional vascular problems. Clin Biomech (Bristol). 2019 Jan;61:211-216. doi: 10.1016/j.clinbiomech.2018.12.020. Epub 2018 Dec 21.
PubMed 30597482
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-invasive Exercise Test for Evaluating Sport-related Arterial Blood Flow Limitation in the Leg: an Exploratory Study (NIRS and Cycling Power in Patients With FLIA)
- ClinicalTrials.gov ID
- NCT05229250
- Acronym / sponsor ID
- NL79767.015.21
- Conditions
- Near-Infrared Spectroscopy, Iliac Artery Stenosis, Iliac Artery Disease, Iliac Artery Occlusion
- Keywords
- FLIA, NIRS, Endofibrosis
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: The hardware failed multiple times. As such we chose to terminate teh study
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Maxima Medical CenterUniversity, hospital or other
- Study start
- 24 Aug 2022 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 8 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The research objectives of this project are to increase the understanding of pathophysiology and performance limitations related to sport-related flow limitation in the iliac artery (FLIA) using non-invasive measurement of muscle oxygenation at the working muscles of the leg and mechanical power output recorded during cycling exercise. Skeletal muscle oxygenation measured with Near-Infrared Spectroscopy (NIRS) is growing more accessible for use by coaches, teams, and individual athletes for use in performance testing. Describing how muscle oxygenation profiles in endurance athletes diagnosed with FLIA differ in comparison with healthy athletes may allow the use of this non-invasive, accessible measurement device for the screening of athletes at risk of developing FLIA.
The relevance of this work is that FLIA imposes risk of irreversible injury to the main artery of the leg in endurance athletes, limiting their ability to participate in exercise, with further consequences for health, fitness, and quality of life. Currently, the early course of this progressive condition is poorly understood, as early detection is difficult and hence appropriate treatment is often delayed. If impairment becomes severe, often more invasive (and risky) treatment is necessary. Earlier detection and monitoring of FLIA may allow for improved patient management and outcomes.
The design of this experiment will compare a patient group of trained cyclists diagnosed with FLIA, to healthy control subjects including cyclists of a similar fitness level without signs of FLIA. Both groups will perform an incremental ramp cycling test and an intermittent multi-stage cycling exercise test. Incremental ramp cycling testing is used as part of clinical diagnosis of FLIA, as well as performance (eg. VO2max) testing of healthy athletes. Multi-stage exercise protocols are also often used for performance testing of endurance athletes and allows for observation of (path)physiological responses during submaximal work stages. Outcome measures of muscle oxygenation kinetics with NIRS and cycling power will be analysed and compared between patients and healthy subjects.
Detailed description
A professional cyclist covers approximately 25,000 km a year and flexes the hip 8,000,000 times in a year, while leg blood flow is in the range of 10-15 litres per minute. This poses a substantial hemodynamic load on the iliac artery. As a result, a proportion of endurance athletes develop a limitation in leg circulation due to arterial narrowing in this iliac artery. An early 'Lancet' study of the department of Sports Medicine of Máxima Medical Centre (MMC) found that 20% of professional cyclists were suffering from such a sport-related Flow Limitation in the Iliac Artery (FLIA) necessitating treatment. The incidence in recreational cyclists is unknown, but with 849,000 recreational cyclists in the Netherlands cycling over 3,000 km a year with an impressive 1,000,000 hip flexions, many of them travel similar distances as a professional cyclist, incurring similar risks for developing FLIA. If untreated, FLIA may have a pronounced impact on quality of life. Professional athletes may have to end their careers prematurely. In a substantial subset of cyclists, abnormalities may even lead to complete occlusion and/or thrombosis, with severe symptoms in daily life.
Clinical experience suggests that early detection and treatment leads to better outcomes. If diagnosed at a late stage, conservative management including changes in training behaviours and body position, or least-invasive surgical repair options will no longer suffice. The only options remaining would be to cease participation in the provocative activities altogether, or to undergo extensive and risky reconstructive vascular surgery. Understanding the early pathogenesis in order to improve detection is thus of paramount importance. Unfortunately, early detection is often missed due to the non-specific presentation of symptoms and the high level of specialisation required for clinical evaluation. There is a wide range of differential diagnoses that could contribute to the non-specific symptoms observed in the early stages of FLIA, including common musculoskeletal and tendinous injuries, mechanical or neurogenic pain referred from the low back or SI joint, hip acetabular labral tear, chronic exertional compartment syndrome, or fibromuscular dysplasia.8 Currently available diagnostic evaluations can have low sensitivity for an athletic population.
There is no single gold-standard evaluation for diagnosing FLIA. The current consensus suggests that the best single functional test is a provocative maximal exercise test on a cycle ergometer, followed by measuring blood pressure at the ankle and brachial arteries (ankle-brachial blood pressure index; ABI) in a competitive posture. In the rare case that the problem is unilateral, the sensitivity is 73%. If the problem is bilateral, the sensitivity is only 43%. Imaging techniques, including echo-Doppler examination, magnetic resonance angiogram (MRA), and computed tomography (CT) scan are more sensitive, but they are more expensive, less accessible, and not part of primary care evaluation, instead being typically reserved for investigation of more severe or complex presentations, and to guide surgical repair.
Near-infrared Spectroscopy (NIRS) is an innovative technique that measures relative oxygenation in the muscle, as the balance of oxygenated and deoxygenated haemoglobin and myoglobin. Impaired arterial leg circulation, such as observed in peripheral vascular disease (PVD) has been shown to produce a drop in oxygen saturation of skeletal muscle tissue relative to workload or exercise performance, and delays in reoxygenation kinetics after exercise and ischemic vascular occlusion tests (VOT). Consequently, NIRS may be able to detect alterations in oxygenation that are associated with the level of arterial insufficiency. We recently reported proof of concept studies regarding the potential diagnostic role of both power output and NIRS in patients with diagnosed sport-related FLIA.
Complaints reported in the early stages of FLIA are powerlessness and pain in the leg muscles when cycling near maximal exertion, which rapidly disappear with rest. Traditionally, incremental ramp cycling exercise to maximal exercise tolerance has been used as a provocative functional test, after which clinical outcome measures including ABI are tested. As the condition progresses however, symptoms can occur earlier during exercise at a lower intensity and take longer to resolve during recovery. Multi-stage exercise protocols are commonly used to understand metabolic responses related to submaximal exercise intensity. Therefore, a progressive multi-stage cycling protocol with brief recovery intervals between work intervals will be introduced. This protocol is designed to allow for multiple opportunities to evaluate work and recovery responses in an intensity-dependent manner. Subjective symptoms, performance impairments (including limitations to cycling power output) and muscle oxygenation kinetic delays will be evaluated across submaximal workloads including after maximal intensity.
Understanding the onset of symptoms and objective signs of flow limitation with progressive exercise intensity will improve understanding of severity and progression of this condition. These outcome measures will be compared to healthy subjects, in order to develop normative values related to healthy performance, compared to pathological impairment. The use of a common multi-stage performance assessment protocol will improve the applicability of using this approach for screening and early detection of FLIA outside of a specialised vascular clinic.
It has been suggested that altered vascular function and structure may contribute to the appearance of symptoms in patients in which obvious stenosis or intraluminal disease is not apparent on imaging. In addition to standard clinical evaluation of the aortoiliac tract with echo-Doppler ultrasound, vascular flow velocity will be recorded for later offline analysis of pulse wave velocity as a measurement of arterial stiffness.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy subjects | – | Other: Cycling test, Other: Occlusion tests, Device: NIRS during cycling, Device: CPET, Device: Echo-Doppler examinationSubjects without FLIA |
| Patient subjects | – | Other: Cycling test, Other: Occlusion tests, Device: NIRS during cycling, Device: CPET, Device: Echo-Doppler examinationSubjects with FLIA |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Patients will be recruited after the diagnosis of FLIA is given during weekly standard clinical care. Healthy subjects will be recruited from local cycling clubs. They completed a standardized questionnaire excluding presence of risk factors such as smoking and positive cardiovascular family history. Candidates with FLIA were excluded. Candidates who fulfilled all study criteria, served as the control group
Key inclusion criteria (2 listed)
- Aged ≥ 18 years and ≤ 40 years
- Trained cyclist or triathlete regularly training at least ~3/week for at least five years and identifying with a particular cycle-sport
Key exclusion criteria (9 listed)
- Earlier vascular iliac surgery
- Microvascular abnormalities (e.g. diabetes),
- Vascular abnormalities outside of the iliac region,
- Heart failure (New York Heart Association class >I),
- Orthopedic/neurological entities potentially limiting exercise capacity,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cycling testRAMP and MULTI-STAGE test | Other | Healthy subjects, Patient subjects |
| Occlusion testsOcclusion test before and after exercise | Other | Healthy subjects, Patient subjects |
| NIRS during cyclingNIRS devices measuring oxygenation during exercise | Device | Healthy subjects, Patient subjects |
| CPETCardiopulmonary exercise testing (heart rate, pulmonary gas exchange) during exercise | Device | Healthy subjects, Patient subjects |
| Echo-Doppler examinationPeak systolic velocity and vascular stiffness measurements in the iliac-aortic tract | Device | Healthy subjects, Patient subjects |
Primary outcome
Power-deoxygenation (PD) profile
Time frame: During cyclingtest day 1
Power-deoxygenation (PD) profile: The ratio of power output to deoxygenation (eg. power/deoxy[heme]) as a proxy for the metabolic disturbance at the working muscle relative to the workload.
Near Infrared Spectroscopy (NIRS) deoxygenation parameters
Time frame: During cyclingtest day 1
Baseline: Average 60-second value before the start of exercise. min: the minimum 5-second mean value attained during exercise. max: the maximum 5-second mean value attained typically during the recovery after exercise. Δexercise amplitude: the difference between baseline and minimum values.
Near Infrared Spectroscopy (NIRS) deoxygenation parameters
Time frame: During cyclingtest day 2
Baseline: Average 60-second value before the start of exercise. min: the minimum 5-second mean value attained during exercise. max: the maximum 5-second mean value attained typically during the recovery after exercise. Δexercise amplitude: the difference between baseline and minimum values.
NIRS delta_recovery amplitude
Time frame: During cyclingtest day 1
The difference between minimum and maximum value.
NIRS delta_recovery amplitude
Time frame: During cyclingtest day 2
The difference between minimum and maximum value.
NIRS reoxygenation kinetics: tau
Time frame: Immediately after exercise day 1
Time constant (tau, in seconds): the time constant parameter of a monoexponential curve fit to the reoxygenation profile after each work stage.
NIRS reoxygenation kinetics: Time delay
Time frame: Immediately after exercise day 1
Time delay (TD, in seconds): the delay before systematic rise in oxygenation after each work stage.
NIRS reoxygenation kinetics: Mean Response Time
Time frame: Immediately after exercise day 1
Mean response time (MRT, in seconds): the sum of TD and tau.
NIRS reoxygenation kinetics: Half value time
Time frame: Immediately after exercise day 1
Half value recovery time (HVT, in seconds): the time required to reoxygenate half of the total amplitude during recovery after each work stage.
NIRS reoxygenation kinetics: Peak reoxygenation rate
Time frame: Immediately after exercise day 1
Peak reoxygenation rate (SmO2/sec): a linear estimation of the peak resaturation slope, representing the magnitude of greatest mismatch between oxygen supply and utilization at the tissue during recovery kinetics, after each work stage.
NIRS reoxygenation kinetics: Peak reoxygenation MRT
Time frame: Immediately after exercise day 1
Peak reoxygenation MRT: an estimate of the time to occurrence of the peak reoxygenation rate, analogous to the MRT in a monoexponential curve, and representing the balance of recovery kinetics of oxygen supply and utilization in the tissue after each work stage.
NIRS reoxygenation kinetics: tau
Time frame: Immediately after exercise day 2
Time constant (tau, in seconds): the time constant parameter of a monoexponential curve fit to the reoxygenation profile after each work stage.
NIRS reoxygenation kinetics: Time delay
Time frame: Immediately after exercise day 2
Time delay (TD, in seconds): the delay before systematic rise in oxygenation after each work stage.
NIRS reoxygenation kinetics: Mean response time
Time frame: Immediately after exercise day 2
Mean response time (MRT, in seconds): the sum of TD and tau.
NIRS reoxygenation kinetics: Half Value time
Time frame: Immediately after exercise day 2
Half value recovery time (HVT, in seconds): the time required to reoxygenate half of the total amplitude during recovery after each work stage.
NIRS reoxygenation kinetics: Peak reoxygenation rate
Time frame: Immediately after exercise day 2
Peak reoxygenation rate (SmO2/sec): a linear estimation of the peak resaturation slope, representing the magnitude of greatest mismatch between oxygen supply and utilization at the tissue during recovery kinetics, after each work stage.
NIRS reoxygenation kinetics: Peak reoxygenation MRT
Time frame: Immediately after exercise day 2
Peak reoxygenation MRT: an estimate of the time to occurrence of the peak reoxygenation rate, analogous to the MRT in a monoexponential curve, and representing the balance of recovery kinetics of oxygen supply and utilization in the tissue after each work stage.
12 secondary outcomes
Recovery kinetics VO2/NIRS comparison
Time frame: After stages/maximal exercise. This is an offline analyses and therefore takes the time of the stage (1 minute for in between blocks; 5 minutes for maximal exercise)
Vascular Occlusion Test - Reactive Hyperemia Area Under The Curve
Time frame: Before cycling test day 1
Multiple reoxygenation kinetics - Primary Component Time constant tau
Time frame: Between intervention day 1 (1-minute stages of block-protocol) and immediately after the intervention day 2 (ramp maximal test)
Multiple reoxygenation kinetics - Cardiodynamic component time delay
Time frame: Between intervention day 1 (1 minustages of block-protocol) and immediately after the intervention day 2 (ramp maximal test)
Multiple reoxygenation kinetics - Δdeoxy[heme] / ΔVO2 onset kinetics
Time frame: During intervention day 1 (stages of block-protocol)
Multiple reoxygenation kinetics - Δdeoxy[heme] / ΔVO2 recovery kinetics
Time frame: Between intervention day 1 (stages of block-protocol) and immediately after the intervention day 2 (ramp maximal test)
Vascular Occlusion Test (VOT): Microvascular Responsiveness
Time frame: Before and after cycling test day 1
Vascular Occlusion Test (VOT): Reactive Hyperemia
Time frame: Before and after cycling test day 1
Clinical Assessment
Time frame: During the same examination-appointment. The PSV will be measured following measurments of the arterial stiffness. This takes about 10 minutes for both sides.
Clinical Assessment
Time frame: Immediately after maximal exercise day 1
Clinical Assessment
Time frame: Immediately after maximal exercise day 2
Clinical Assessment
Time frame: Before exercise day 1, the arterial stiffness will be measured by the vascular technician. While this will be analyzed offline, this takes a few minutes.
Results and safety
The study was stopped early (reason given: The hardware failed multiple times. As such we chose to terminate teh study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Background: PubMed 32713244van Hooff M, Schep G, Bender M, Scheltinga M, Savelberg H. Sport-related femoral artery occlusion detected by near-infrared spectroscopy and pedal power measurements: a case report. Phys Sportsmed. 2021 May;49(2):241-244. doi: 10.1080/00913847.2020.1796182. Epub 2020 Jul 26.
- Background: PubMed 30671480van Hooff M, Schep G, Meijer E, Bender M, Savelberg H. Near-Infrared Spectroscopy Is Promising to Detect Iliac Artery Flow Limitations in Athletes: A Pilot Study. J Sports Med (Hindawi Publ Corp). 2018 Dec 20;2018:8965858. doi: 10.1155/2018/8965858. eCollection 2018.
- Background: PubMed 11853791Schep G, Bender MH, van de Tempel G, Wijn PF, de Vries WR, Eikelboom BC. Detection and treatment of claudication due to functional iliac obstruction in top endurance athletes: a prospective study. Lancet. 2002 Feb 9;359(9305):466-73. doi: 10.1016/s0140-6736(02)07675-4.
- Background: PubMed 15233596Bender MH, Schep G, de Vries WR, Hoogeveen AR, Wijn PF. Sports-related flow limitations in the iliac arteries in endurance athletes: aetiology, diagnosis, treatment and future developments. Sports Med. 2004;34(7):427-42. doi: 10.2165/00007256-200434070-00002.
- Background: PubMed 22186674Peach G, Schep G, Palfreeman R, Beard JD, Thompson MM, Hinchliffe RJ. Endofibrosis and kinking of the iliac arteries in athletes: a systematic review. Eur J Vasc Endovasc Surg. 2012 Feb;43(2):208-17. doi: 10.1016/j.ejvs.2011.11.019. Epub 2011 Dec 19.
- Background: PubMed 27161328Hinchliffe RJ. Iliac Artery Endofibrosis. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):1-2. doi: 10.1016/j.ejvs.2016.04.006. Epub 2016 May 6. No abstract available.
- Background: PubMed 27209899INSITE Collaborators (INternational Study group for Identification and Treatment of Endofibrosis). Diagnosis and Management of Iliac Artery Endofibrosis: Results of a Delphi Consensus Study. Eur J Vasc Endovasc Surg. 2016 Jul;52(1):90-8. doi: 10.1016/j.ejvs.2016.04.004. Epub 2016 May 17.
- Background: PubMed 30101198Khan A, Al-Dawoud M, Salaman R, Al-Khaffaf H. Management of Endurance Athletes with Flow Limitation in the Iliac Arteries: A Case Series. EJVES Short Rep. 2018 Jul 20;40:7-11. doi: 10.1016/j.ejvssr.2018.06.001. eCollection 2018.
- Background: PubMed 29548540Peake LK, D'Abate F, Farrah J, Morgan M, Hinchliffe RJ. The Investigation and Management of Iliac Artery Endofibrosis: Lessons Learned from a Case Series. Eur J Vasc Endovasc Surg. 2018 Apr;55(4):577-583. doi: 10.1016/j.ejvs.2018.01.018. Epub 2018 Mar 13.
- Background: PubMed 12165882Schep G, Bender MH, Schmikli SL, Mosterd WL, Hammacher ER, Scheltinga M, Wijn PF. Recognising vascular causes of leg complaints in endurance athletes. Part 2: the value of patient history, physical examination, cycling exercise test and echo-Doppler examination. Int J Sports Med. 2002 Jul;23(5):322-8. doi: 10.1055/s-2002-33142.
- Background: PubMed 30844336Barstow TJ. Understanding near infrared spectroscopy and its application to skeletal muscle research. J Appl Physiol (1985). 2019 May 1;126(5):1360-1376. doi: 10.1152/japplphysiol.00166.2018. Epub 2019 Mar 7.
- Background: PubMed 29177977Perrey S, Ferrari M. Muscle Oximetry in Sports Science: A Systematic Review. Sports Med. 2018 Mar;48(3):597-616. doi: 10.1007/s40279-017-0820-1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M van Hooff, MSc principal investigator
Maxima Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Near-Infrared Spectroscopy and Iliac Artery Stenosis, run by Maxima Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The hardware failed multiple times. As such we chose to terminate teh study). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Power-deoxygenation (PD) profile (time frame: During cyclingtest day 1). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05229250, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.