A Study on the Phenomenon of Remote Ischaemic Preconditioning in Patients With Peripheral Artery Disease
Condition: Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases
Study type: Interventional

Summary: 
      This study aims to evaluate whether remote ischemic preconditioning (RIPC) daily for 28 days
      reduces the symptoms of intermittent claudication in patients with peripheral artery disease
      (PAD). The study evaluates the effect of RIPC on patients' total walking distance (TWC),
      initial claudication distance (ICD), and time to relief of claudication (TRC). In addition,
      the trial investigates the effect of RIPC on different arterial functional characteristics
      and low molecular weight metabolites in serum and affected skeletal muscle.
    

Detailed description: 
      A research hypothesis is that repeated remote ischemic preconditioning (RIPC) daily for 28
      days reduces the symptoms of intermittent claudication in patients with peripheral artery
      disease (PAD).

      The investigators plan to conduct a randomized controlled trial. Clinically stable patients
      with PAD and intermittent claudication are randomly allocated to receive a repeated RIPC or
      sham for 28 days. An automated device generates RIPC. One cycle of RIPC consists of 4 cycles
      of 5-min upper limb ischemia followed by 5-min reperfusion (lasting a total of 35 minutes).
      The participant places the device on his upper arm and presses the "Start "button, starting
      the intervention. The intervention occurs at rest in the participant's home environment. The
      first intervention takes place in the research center, where the research assistant teaches
      the participant how to use the device. In the sham group, a RIPC imitation is performed. The
      sham device has the same sound and light effects as the active device; the only difference is
      that the pressure in the cuff does not increase, so ischemia does not occur.

      Randomization is performed using blocks. Each block has 2-4 subjects. Subjects are divided
      according to smoking status (active smoker yes/no) and age (≥ 65 years or < 65 years old).
      Randomized letters (whether the subject will go into the experimental group or the sham
      group) are placed in opaque envelopes, which are opened right before the first intervention.

      Participants will visit the research center twice. During the first visit, they fill in the
      VASCUQOL-6 questionnaire to evaluate their symptoms and health-related quality of life. In
      addition, the investigators collect participants' blood and urine samples, measure their
      arterial stiffness parameters and assess symptom-free and maximal walking distance on a
      treadmill. The investigators will take a skeletal muscle biopsy from the first ten
      participants in each group using a tiny percutaneous needle biopsy (TPNB) technique to
      measure low molecular weight metabolites in affected skeletal muscle.

      These steps are repeated on the second visit (after 28 days of intervention). After data
      collection is completed, a statistical analysis is performed to evaluate whether RIPC
      improves participants' maximal walking distance, arterial stiffness, and metabolic
      parameters.
    

Intervention name(s): Repeated remote ischemic preconditioning; Simulation of repeated remote ischemic preconditioning (sham)
Intervention type(s): Other; Other
Intervention description(s): An automated device performs four 5-minute episodes of upper limb ischemia in which the cuff pressure in the experimental group remains at 200 mmHg for 5 minutes, causing and ensuring ischemia. Ischemic episodes alternate with 5-minute reperfusion. The intervention lasts a total of 35 minutes. The participant places the device on his upper arm and presses the "Start" button, starting the intervention. The intervention takes place at rest in the patient's home environment daily for 28 days. During the first visit to the research center, the research assistant teaches the participant how to use the device. The device measures the patient's blood pressure at the start of the intervention. If the patient's blood pressure is above 200 mmHg, the device will not perform the intervention.; The automated device simulates the intervention of the experimental group with the difference that the device does not apply pressure to the upper limb and, therefore, no ischemia occurs.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Intermittent Claudication; Total Walking Distance; Initial Claudication Distance; Time to Relief of Claudication; Arterial Stiffness; VASCUQOL-6; Peripheral Artery Disease