Local or Systemic Effects: Mechanisms Related to Arm Crank Exercise - Comparison Between Individuals With and Without PAD

Local or Systemic Vascular Effects: Mechanisms Related to Arm Crank Exercise - Comparison Between Individuals With and Without PAD

INTRODUCTION: Exercise with an arm ergometer (EB) overcomes the main barrier to physical exercise in patients with Peripheral Artery Disease (PAD), leg pain during walking. Due to its aerobic nature, this type of exercise can cause systemic changes in the regulatory mechanisms of vasodilation. In other words, it provides vascular benefits in the most affected arterial beds in the PAD population. OBJECTIVE: To analyze local and systemic vascular responses, as well as cell signaling pathways after an EB exercise session in patients with PAD and their peers without PAD. METHODS: 24 patients with PAD and 24 individuals without PAD will be recruited, matched by sex and age. Participants will undergo two experimental sessions in approved order (EB and control). The EB session will consist of 15 cycles of 2 min of exercise with an intensity equivalent to 13-15 on the Borg scale of perceived exertion. Before and after the experimental sessions, the vascular function of the brachial and femoral arteries, blood indicators of vasodilation and calf muscle oxygenation will be evaluated. To analyze the acute effect between groups on cardiovascular parameters, a three-way analysis of variance will be performed, taking as factors disease (presence vs. absence), session (EB vs. Control) and time (pre vs. post). In all analyses, when a significant effect is selected, the Bonferroni or Newman-Keuls post-hoc test will be used. For all analyses, a value of P<0.05 will be considered significant.

Study Overview

• Status: Enrolling by invitation
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Behavioral: Exercise

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01525-000
      • University Nove de Julho

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• If female, must be postmenopausal without hormone replacement therapy;
• Non-smokers;
• With a body mass index (BMI) not exceeding 30 kg/m²;
• With calf skinfold thickness below 20 mm, due to the interference of adiposity in the penetration of light from the NIRS probe, and oxygen saturation in the finger >95% to ensure that impaired pulmonary gas exchange does not affect oxygen saturation measurements in the calf;
• Not using classic antioxidants or vitamin supplements; and
• Physically capable of performing an exercise session.
• For the group of participants with PAD, in addition to the criteria mentioned above, they must have a confirmed diagnosis of the disease, characterized by an ankle-brachial index (ABI) lower than 0.90 in one or both legs, exhibit symptoms of claudication during walking, and be physically capable of performing an exercise session to participate in the project.

Exclusion Criteria:

• Only participants who discontinue their participation in the study protocol will be excluded from the sample

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control Condition; The control condition will consist of resting in the standing position for thirty minutes. The patients will be instructed to rest in the sitting position for two minutes at periods equivalent to the intervals from the exercise conditions, totalling sixty minutes of duration.	Behavioral: Exercise; Two conditions will be tested: Arm-cranking and control condition.
Experimental: Arm crank exercise; In the arm-cranking condition, the patients will perform fifteen bouts of two minutes of arm-cranking with an interval of two minutes between bouts, at an intensity equivalent to 13-15 on Borg's subjective perceived exertion scale. The condition will have a total of sixty minutes of duration.	Behavioral: Exercise; Two conditions will be tested: Arm-cranking and control condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calf Muscle Oxygen Saturation (%)	The parameters of calf muscle oxygenation will be collected using the non-invasive Near-Infrared Spectroscopy (NIRS) technique, with an NIRS spectrometer and a dedicated laptop computer. The NIRS sensor will be placed on the calf region, on the leg with the lower ankle brachial index, at the level of the largest calf circumference. The equipment will be programmed for continuous recording throughout the experimental session, covering the pre-exercise, during exercise with arm ergometer, and post-exercise periods.	Just before, during 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 minutes of exercise, and after 10 minutes of exercise.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxyhemoglobin (micromol)	The parameters of calf muscle oxygenation will be collected using the non-invasive Near-Infrared Spectroscopy (NIRS) technique, with an NIRS spectrometer and a dedicated laptop computer. The NIRS sensor will be placed on the calf region, on the leg with the lower ankle brachial index, at the level of the largest calf circumference. The equipment will be programmed for continuous recording throughout the experimental session, covering the pre-exercise, during exercise with arm ergometer, and post-exercise periods.	Just before, during 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 minutes of exercise, and after 10 minutes of exercise.
Deoxyhemoglobin (micromol)	The parameters of calf muscle oxygenation will be collected using the non-invasive Near-Infrared Spectroscopy (NIRS) technique, with an NIRS spectrometer and a dedicated laptop computer. The NIRS sensor will be placed on the calf region, on the leg with the lower ankle brachial index, at the level of the largest calf circumference. The equipment will be programmed for continuous recording throughout the experimental session, covering the pre-exercise, during exercise with arm ergometer, and post-exercise periods.	Just before, during 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 minutes of exercise, and after 10 minutes of exercise.
Total hemoglobin (micromol)	The parameters of calf muscle oxygenation will be collected using the non-invasive Near-Infrared Spectroscopy (NIRS) technique, with an NIRS spectrometer and a dedicated laptop computer. The NIRS sensor will be placed on the calf region, on the leg with the lower ankle brachial index, at the level of the largest calf circumference. The equipment will be programmed for continuous recording throughout the experimental session, covering the pre-exercise, during exercise with arm ergometer, and post-exercise periods.	Just before, during 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 minutes of exercise, and after 10 minutes of exercise.
Change from baseline in vascular function post-exercise in the brachial and femoral arteries (%).	Vascular function will be measured in the supine position by the flow-mediated dilation (FMD) technique, through Doppler ultrasonography.	Before and after 40 minutes of exercise.
Nitric oxide production markers (micromol)	Before and after the sessions, a venous blood sample (10 mL) will be collected in tubes containing Ethylenediaminetetraacetic Acid (EDTA). Plasma will be immediately obtained after refrigerated centrifugation and used for the determination of thiobarbituric acid reactive substances (TBARS), nitrite, and nitrate (Griess test, Sigma Aldrich), as well as for biochemical analyses of lipids (cholesterol, triglycerides, High-Density Lipoprotein (HDL) cholesterol, and Low-Density Lipoprotein (LDL) cholesterol calculation) and glucose levels. Glycated hemoglobin will be determined in whole blood by high-performance liquid chromatography. Cultured human umbilical vein endothelial cells (HUVEC) will be incubated with 0.2% plasma obtained from all individuals for different time intervals. Indicators of nitric oxide production will be determined in the cells (cGMP concentration and endothelial nitric oxide synthase [eNOS] expression) and in the culture medium (nitrite/nitrate concentration).	Before and after 5 minutes of exercise.

Collaborators and Investigators

• Sponsor: University of Nove de Julho
• Collaborators: University of Sao Paulo; Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Investigators: Principal Investigator: Marilia A Correia, PhD, University of Nove de Julho

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2025
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): July 15, 2027

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): February 14, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Vascular function; Intermittent claudication
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Peripheral Arterial Disease; Intermittent Claudication; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: EB_PADvsHealth

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual data may be disclosed upon contact with the principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No