Conditioning Based Intervention Strategies

NCT03380663 | Unknown DMC

• 1 other identifier: ConBIS
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this study is to uncover and utilize the mechanisms behind the activation of endogenous organ protection by remote ischemic conditioning (RIC), high intensity traditional resistance training (TRT) and low intensity blood flow restricted resistance exercise (BFRE) with the perspective of defining their applicability for immediate organ protection in ischemia-reperfusion injury (acute conditioning) and subsequent tissue repair (chronic conditioning) during a prolonged recovery period. This objective will be achieved by studying which and how molecular pathways underlying these protective mechanisms are shared and can be transferred to treat medical conditions. A specific focus is the roles of EVs and miRNAs. Another objective is to explore how exercise training with and without ischemia can counteract muscle wasting.

Conditions

Ischemic Preconditioning

Keywords

blood flow restricted resistance exercise; remote ischemic conditioning; miRNA

Outcome Measures

Primary Outcomes (1)

• Changes in miRNA and EV content in blood samples

  Analyzing miRNA sequences

  6 Weeks

Secondary Outcomes (5)

• Effects on muscle endurance

  6 weeks

• Effects on inflammatory state

  6 weeks

• Changes in skeletal muscle myofibrillar and mitochondrial protein synthesis

  6 weeks

• Protection against IR injury in isolated rat/rabbit hearts and isolated cells

  6 weeks

• Changes in skeletal muscle growth and strength

  6 weeks

Study Arms (7)

RIC - Healthy

ACTIVE COMPARATOR

Healthy subjects undergoing Remote Ischemic Conditioning (RIC) by inducing 3 or 4 five-minute cycles of limb ischemia and reperfusion using a tourniquet.

Procedure: Remote Ischemic Conditioning (RIC)

RIC - HF

ACTIVE COMPARATOR

Heart failure patients undergoing Remote Ischemic Conditioning (RIC) by inducing 3 or 4 five-minute cycles of limb ischemia and reperfusion using a tourniquet.

Procedure: Remote Ischemic Conditioning (RIC)

BFRE - Healthy

ACTIVE COMPARATOR

Healthy subjects undergoing low intensity blood flow restricted resistance exercise (BFRE) conducting 4 sets of bilateral knee extensions at 30% of 1RM until concentric contraction failure. The sets are intercepted by 30 seconds of rest (during rest the cuff's are still inflated).

Procedure: Remote Ischemic Conditioning (RIC)

BFRE - HF

ACTIVE COMPARATOR

Heart failure patients undergoing low intensity blood flow restricted resistance exercise (BFRE) conducting 4 sets of bilateral knee extensions at 30% of 1RM until concentric contraction failure. The sets are intercepted by 30 seconds of rest (during rest the cuff's are still inflated).

Procedure: Remote Ischemic Conditioning (RIC)

TRT - Healthy

ACTIVE COMPARATOR

Healthy subjects undergoing heavy intensive resistance training (TRT) undergoing 4 sets of 10-12 repetitions are performed in the knee extensor machine - load equaling 15RM and rest for 3 minutes).

Procedure: Remote Ischemic Conditioning (RIC)

Control - Healthy

NO INTERVENTION

No intervention.

Control - HF

NO INTERVENTION

No intervention.

Interventions

Remote Ischemic Conditioning (RIC) PROCEDURE

Remote Ischemic Conditioning (RIC) is a new treatment modality to attenuate reperfusion injury. Organ protection by RIC can be achieved simply by inducing 3 or 4 five-minute cycles of limb ischemia and reperfusion using a tourniquet or simple blood pressure cuff Ischemic resistance exercise training conducted as low-intensity blood flow restricted resistance exercise (BFRE), with a low occlusion pressure stimulus, which only compromises venous but not arterial blood flow. Much like RIC, BFRE is conducted as 3-5 cycles (sets of exercise) interspaced by short duration of recovery. High intensity traditional resistance training (TRT) is performed by sets of 10-12 repetitions are performed in the knee extensor machine - load equaling 15RM and rest for 3 minutes).

Also known as: Blood Flow Restricted resistance Exercise (BFRE), Traditional Resistance Training (TRT)

BFRE - HF; BFRE - Healthy; RIC - HF; RIC - Healthy; TRT - Healthy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years
• Able to sit in a knee extension machine
• Able to deliver muscle biopsies
• Able to train 3 times per week during a 6-week period
• Chronic congestive ischemic heart failure
• LV ejection fraction ≤45%
• NYHA function class II-IV

You may not qualify if:

• Myocardial infarction
• Angina pectoris
• Pregnancy
• Diabetes mellitus
• Peripheral neuropathy
• Dialysis treatment
• Severe peripheral arterial disease
• Concomitant acute life threatening medical condition
• Medications known to modify the effect of ischemic conditioning such as cyclosporin and glibenclamide.
• Recent cardiovascular hospitalization (within last 30 days)
• Intracranial aneurisms, arteriovenous malformation, cerebral neoplasm or abscess.
• Myocardial infarction
• Angina pectoris
• Severe arterial hypertension (≥ 180/≥ 110 mmHg) or moderate arterial hypertension (160-179/100-109) despite medical treatment.
• Moderate to severe cardiac valve disease

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University

Aarhus, 8000, Denmark

RECRUITING

Related Publications (2)

• Lassen TR, Just J, Hjortbak MV, Jespersen NR, Stenz KT, Gu T, Yan Y, Su J, Hansen J, Baek R, Jorgensen MM, Nyengaard JR, Kristiansen SB, Drasbek KR, Kjems J, Botker HE. Cardioprotection by remote ischemic conditioning is transferable by plasma and mediated by extracellular vesicles. Basic Res Cardiol. 2021 Mar 10;116(1):16. doi: 10.1007/s00395-021-00856-w.

  PMID: 33689033 DERIVED

• Groennebaek T, Sieljacks P, Nielsen R, Pryds K, Jespersen NR, Wang J, Carlsen CR, Schmidt MR, de Paoli FV, Miller BF, Vissing K, Botker HE. Effect of Blood Flow Restricted Resistance Exercise and Remote Ischemic Conditioning on Functional Capacity and Myocellular Adaptations in Patients With Heart Failure. Circ Heart Fail. 2019 Dec;12(12):e006427. doi: 10.1161/CIRCHEARTFAILURE.119.006427. Epub 2019 Dec 13.

  PMID: 31830830 DERIVED

Study Officials

• Hans Erik Bøtker, MD, PhD

  Department of Clinical Medicine, Department of Cardiological Medicine, Aarhus University Hospital

  STUDY DIRECTOR

Central Study Contacts

Frank de Paoli, MD, PhD

CONTACT

+45 61460880; fdp@biomed.au.dk

Hans Erik Bøtker, MD, DMSc

CONTACT

+45 78459208; boetker@clin.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A multi-center randomized control study, including single-treatment and repeated treatment trials on individuals suffering from heart failure and healthy control subjects.

Study Record Dates

• First Submitted: August 23, 2017
• First Posted: December 21, 2017
• Study Start: September 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: July 1, 2019
• Last Updated: December 22, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)