Peripheral Arterial DiseaseNCT05084066
A Study on the Phenomenon of Remote Ischaemic Preconditioning in Patients With Peripheral Artery Disease
A study testing Repeated remote ischemic preconditioning in people with Peripheral Arterial Disease, run by Tartu University Hospital at 1 site in Estonia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years, men only
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Repeated remote ischemic preconditioning
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteEstonia
- Study dates
- 24 Jan 2022to 18 Apr 2023
- Phase
- Interventional
- 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 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Peripheral arterial disease, which causes claudication
- Patients who have given written informed consent and are undergoing conservative treatment for claudication (continuous treatment for at least three months)
- Patients with lower limb atherosclerosis Fontaine class IIA or IIB
- The primary limiter of walking is claudication, not any other condition
- Ankle-brachial index (ABI) ≤ 0,9 in symptomatic lower limb
Who cannot join
- Female gender
- Resting blood pressure > 200 mmHg
- Fontaine class III or IV
- eGFR < 30 ml/min/1,73 m2
- Home oxygen therapy or severe COPD (GOLD 3-4)
- Heart failure NYHA III-IV
Show all 17Show fewer
- Stable angina pectoris
- Clinically severe COVID-19 infection in the last three months
- History of malignancy (within the last five years)
- Persistent or permanent atrial fibrillation or flutter
- Acute myocardial infarction in the last three months
- Residual signs of cerebral infarction that impede movement
- Significant atherosclerosis of peripheral arteries of the upper limb (symptomatic)
- History of deep vein thrombosis of the upper limb
- Diabetic polyneuropathy
- Under 18 years of age
- Patients who are unable to follow the study regimen
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Peripheral Arterial Disease
- Being tested
- Repeated remote ischemic preconditioning, Simulation of repeated remote ischemic preconditioning (sham)
- Keywords
- Intermittent Claudication, Total Walking Distance, Initial Claudication Distance, Time to Relief of Claudication, Arterial Stiffness, VASCUQOL-6, Peripheral Artery Disease
- Medical subject headings
- Peripheral Arterial Disease, Intermittent Claudication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repeated remote ischemic preconditioningOther
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.
Simulation of repeated remote ischemic preconditioning (sham)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | 20 patients with PAD and claudication Receives: Other: Repeated remote ischemic preconditioning |
| Control group (sham) | Sham comparator | 20 patients with PAD and claudication Receives: Other: Simulation of repeated remote ischemic preconditioning (sham) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline Total Walking Distance at 28 Days
Maximal walking distance performed on a treadmill test
Measured: 28 days
Secondary outcomes (9)
Change from Baseline Initial Claudication Distance at 28 Days
The distance walked at the onset of claudication pain (assessed on a treadmill test)
Measured: 28 days
Change from Baseline Time to Relief of Claudication at 28 Days
The amount of time it takes for the pain to go away after patient stops walking (assessed with stopwatch)
Measured: 28 days
Change from Baseline Carotid-Femoral Pulse Wave Velocity at 28 Days
A measure of arterial stiffness (measured with SphygmoCor XCEL 7.0)
Measured: 28 days
Change from Baseline Augmentation Index at 28 Days
A parameter of arterial stiffness (measured with SphygmoCor XCEL 7.0)
Measured: 28 days
Change from Baseline Low Molecular Weight Metabolite Levels in Serum at 28 Days
A variety of acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and sugars measured using AbsoluteIDQ® p180 kit
Measured: 28 days
Change from Baseline Low Molecular Weight Metabolite Levels in Muscle Biopsy Specimen at 28 Days
A variety of acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and sugars measured using AbsoluteIDQ® p180 kit
Measured: 28 days
Change from Baseline Health-Related Quality of Life in PAD at 28 Days
Measured with Vascular Quality of Life Questionnaire-6 (VASCUQOL-6 questionnaire). The questionnaire consists of six questions. Every question has a 4-point response scale. An overall score ranges from 6 (worst) to 24 (best health-related quality of life) when summarizing the points.
Measured: 28 days
Incidence of Major Adverse Cardiovascular Events (MACE) One Year after the Intervention
Incidence of myocardial infarction, stroke, hospitalization because of heart failure and revascularization, including percutaneous coronary intervention and coronary artery bypass graft one year after the intervention
Measured: One year after the intervention
Incidence of Major Limb Events (MALE) One Year after the Intervention
Incidence of acute limb ischemia, including thrombectomy and thrombolysis, major amputation at or above the ankle, or need for surgical peripheral revascularization one year after the intervention
Measured: One year after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2021
- Study start24 Jan 2022
- Primary completion18 Apr 2023
- Study completion18 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tartu University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jaak Kals, University of Tartu
- Investigators
- Jaak Kals, PhD, Principal investigator, University of Tartu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05084066
- Sponsor's protocol ID
- 21082
- Status last verified
- Oct 2023
- First submitted
- 21 Sep 2021
- Last updated
- 10 Oct 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eerik K, Kasepalu T, Post H, Eha J, Kals M, Bjorck M, Kals J. Effects of Repeated Remote Ischaemic Preconditioning on Arterial Stiffness, Organ Damage, and Oxidative Stress in Patients with Intermittent Claudication: A Sham Controlled Randomised Trial. Eur J Vasc Endovasc Surg. 2026 Jan;71(1):117-123. doi: 10.1016/j.ejvs.2025.06.046. Epub 2025 Jun 24.
PubMed 40571146Eerik K, Kasepalu T, Post H, Eha J, Kals M, Kals J. Editor's Choice - Daily Remote Ischaemic Preconditioning for Intermittent Claudication: A Sham Controlled Randomised Trial. Eur J Vasc Endovasc Surg. 2025 Feb;69(2):295-302. doi: 10.1016/j.ejvs.2024.10.047. Epub 2024 Nov 8.
PubMed 39522584
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study on the Phenomenon of Remote Ischaemic Preconditioning in Patients With Peripheral Artery Disease
- ClinicalTrials.gov ID
- NCT05084066
- Acronym / sponsor ID
- 21082
- Conditions
- Peripheral Arterial Disease
- Keywords
- Intermittent Claudication, Total Walking Distance, Initial Claudication Distance, Time to Relief of Claudication, Arterial Stiffness, VASCUQOL-6, Peripheral Artery Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Tartu University HospitalUniversity, hospital or other
- Study start
- 24 Jan 2022 (actual)
- Primary completion
- 18 Apr 2023 (actual)
- Study completion
- 18 Apr 2023 (actual)
- First posted
- 19 Oct 2021 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Other: Repeated remote ischemic preconditioning20 patients with PAD and claudication |
| Control group (sham) | Sham comparator | Other: Simulation of repeated remote ischemic preconditioning (sham)20 patients with PAD and claudication |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Peripheral arterial disease, which causes claudication
- Patients who have given written informed consent and are undergoing conservative treatment for claudication (continuous treatment for at least three months)
- Patients with lower limb atherosclerosis Fontaine class IIA or IIB
- The primary limiter of walking is claudication, not any other condition
- Ankle-brachial index (ABI) ≤ 0,9 in symptomatic lower limb
Key exclusion criteria (17 listed)
- Female gender
- Resting blood pressure > 200 mmHg
- Fontaine class III or IV
- eGFR < 30 ml/min/1,73 m2
- Home oxygen therapy or severe COPD (GOLD 3-4)
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 |
|---|---|---|
| Repeated remote ischemic preconditioningAn 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. | Other | Experimental group |
| Simulation of repeated remote ischemic preconditioning (sham)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. | Other | Control group (sham) |
Primary outcome
Change from Baseline Total Walking Distance at 28 Days
Time frame: 28 days
Maximal walking distance performed on a treadmill test
9 secondary outcomes
Change from Baseline Initial Claudication Distance at 28 Days
Time frame: 28 days
Change from Baseline Time to Relief of Claudication at 28 Days
Time frame: 28 days
Change from Baseline Carotid-Femoral Pulse Wave Velocity at 28 Days
Time frame: 28 days
Change from Baseline Augmentation Index at 28 Days
Time frame: 28 days
Change from Baseline Low Molecular Weight Metabolite Levels in Serum at 28 Days
Time frame: 28 days
Change from Baseline Low Molecular Weight Metabolite Levels in Muscle Biopsy Specimen at 28 Days
Time frame: 28 days
Change from Baseline Health-Related Quality of Life in PAD at 28 Days
Time frame: 28 days
Incidence of Major Adverse Cardiovascular Events (MACE) One Year after the Intervention
Time frame: One year after the intervention
Incidence of Major Limb Events (MALE) One Year after the Intervention
Time frame: One year after the intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- Derived from this study: PubMed 40571146Eerik K, Kasepalu T, Post H, Eha J, Kals M, Bjorck M, Kals J. Effects of Repeated Remote Ischaemic Preconditioning on Arterial Stiffness, Organ Damage, and Oxidative Stress in Patients with Intermittent Claudication: A Sham Controlled Randomised Trial. Eur J Vasc Endovasc Surg. 2026 Jan;71(1):117-123. doi: 10.1016/j.ejvs.2025.06.046. Epub 2025 Jun 24.
- Derived from this study: PubMed 39522584Eerik K, Kasepalu T, Post H, Eha J, Kals M, Kals J. Editor's Choice - Daily Remote Ischaemic Preconditioning for Intermittent Claudication: A Sham Controlled Randomised Trial. Eur J Vasc Endovasc Surg. 2025 Feb;69(2):295-302. doi: 10.1016/j.ejvs.2024.10.047. Epub 2024 Nov 8.
- 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.
Jaak Kals, PhD principal investigator
University of Tartu
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repeated remote ischemic preconditioning in people with Peripheral Arterial Disease, run by Tartu University Hospital at 1 site in Estonia.
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 5 inclusion and 17 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: finished, as of the sponsor's last update on 10 Oct 2023. 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 Estonia. 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. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change from Baseline Total Walking Distance at 28 Days (time frame: 28 days). 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 NCT05084066, which also lists 2 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 10 Oct 2023.