Chronic Heart FailurePhase 2BFR-CHFNCT03342833
Blood Flow Restriction Training in Chronic Heart Failure: an Effective Training Strategy?
A Phase 2 study testing Blood flow restriction in people with Chronic Heart Failure, run by University of Leeds at 1 site in United Kingdom.
Trial summary
The purpose of this current study proposal is to identify the potential physiological adaptations arising from a combined BFR+HIIT training intervention in CHF patients. We hypothesise that the addition of BFR to HIIT will increase whole-body V̇O2peak by promoting vascular and skeletal muscle adaptations above that… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Heart Failure
- What is being tested?
- Blood flow restriction
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Mar 2018to 1 Apr 2021
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with New York Heart Association (NYHA) class II-III symptoms Stable CHF of at least 3 months duration On optimally tolerated medication for CHF No contraindications for cycling exercise Able and willing to give informed consent
Who cannot join
- Class IV CHF Any contraindications to exercise Significant COPD (FEV1<60%), severe renal disease (eGFR<30), primary pulmonary hypertension as a co-morbidity Unable to give informed consent Current diagnosis of active cancer, inflammatory or musculoskeletal disease (e.g. rheumatoid arthritis), on-going infection or sepsis.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Leeds Teaching Hospitals NHS Trust
Leeds, West Yorkshire, LS16 5AR
About this study
The purpose of this current study proposal is to identify the potential physiological adaptations arising from a combined BFR+HIIT training intervention in CHF patients. We hypothesise that the addition of BFR to HIIT will increase whole-body V̇O2peak by promoting vascular and skeletal muscle adaptations above that seen with HIIT alone. The secondary outcomes of this study are to determine if such a training intervention leads to clinical improvements in exercise intolerance symptoms and quality of life indices. Given that the majority of previous research in to both BFR and HIIT has largely involved young, healthy and relatively active participants, the final objective of this current proposal is to determine the viability, tolerability and efficacy of these training modalities in an elderly cohort of predominantly sedentary CHF patients.
Read the detailed description
Exercise training in CHF is a potentially effective intervention for improving symptomatic and prognostic outcomes, but remains underutilised in contemporary CHF management in the United Kingdom. This underutilisation may be partly the result of multiple approaches to training but also due to inconsistent and overall modest results of any of the interventions on important patient-orientated outcomes. A key consideration in this latter regard is whether disease related symptoms (e.g. dyspnoea) during exercise training limit the physiological work achievable during training, limiting the degree of the training stimulus to below the level at which physiological adaptation can be achieved. For example, in COPD participants only those in whom skeletal muscle fatigue was present after a training session evidenced any improvement in functional exercise capacity and health-related quality of life following a 3-month rehabilitation programme. Investigating novel approaches to training that promote greater gains in training effect may therefore lead to greater changes in patient-centred outcomes which will eventually stimulate greater uptake and alleviate the clinical burden chronic heart failure.
Blood Flow Restriction (BFR) training is a novel strategy in which a pressure cuff is inflated around the proximal portion of the exercising limbs (e.g. at the top of the arms or legs) during exercise or in recovery periods between exercise bouts. The pressure of the cuff is set to allow arterial blood flow but occlude venous return, subsequently altering (or maintaining) the local metabolic milieu, resulting in upregulation of several downstream pathways that augment the adaptive response to exercise. BFR has been successfully employed previously in combination with resistance exercise (RE) training to augment skeletal muscle hypertrophy in isolated peripheral muscles. Importantly, this training has been shown to promote muscle hypertrophy with concomitant increases in isokinetic strength in elderly individuals performing at low exercise work rates. This therefore demonstrates that BFR can induce comparatively similar adaptations at a lower power in elderly populations, suggesting this training strategy may have applications in other groups, such as CHF patients.
Additional studies have also demonstrated improvements in V̇O2peak by combining BFR with traditional low-intensity endurance training or high-intensity interval training (HIIT). Using a within-measures design, the first of these studies demonstrated that a 4-week training intervention (4 sessions per week) of 45-mins single-leg cycling under ischaemic conditions (induced by an external pressure of 50 mmHg in a pressure chamber) improved time-to-fatigue and V̇O2peak significantly more than an identical training intervention on the contralateral leg under normoxic (non-ischaemic) conditions. Further research with a between-measures design showed that 8-weeks of low-intensity cycling (40% V̇O2peak) with continuous BFR (160-210 mmHg) can increase both muscle strength and cross-sectional area as well as V̇O2peak significantly more than a control intervention using the same protocol without BFR. Interestingly, the control group exercised for longer during their training sessions (45-mins vs 15-mins for BFR) demonstrating that BFR not only has the potential to augment adaptations but is also a time-efficient modality of exercise. Given that lack of time is frequently cited as a barrier to regular exercise training, novel training interventions, such as BFR, that aren't time-consuming may be considered an attractive alternative form of exercise.
HIIT is also promoted as a time-efficient training modality that is known to promote comparable physiological adaptations to traditional high-volume low-intensity endurance exercise training. HIIT typically involves repeated bouts of intense ('near-maximal') exercise separated by brief periods of recovery. Some training studies have now combined BFR with HIIT (BFR+HIIT), applying the pressure cuff during recovery periods rather than during exercise. This combination of BFR+HIIT allows the working muscle to perform as normal during the short bouts of exercise; however, application of the cuff during recovery was shown to promote superior physiological adaptations above HIIT alone. Specifically, this study demonstrated that 4-weeks (2 sessions per week) of sprint interval training (4-7 bouts of maximal 30s cycling sprints with 4.5-mins recovery) combined with BFR (2-mins at 130 mmHg during the recovery period) significantly increased V̇O2peak compared to a control group performing the same training protocol without BFR.
Although the exact mechanisms responsible for this superior physiological response have yet to be fully elucidated, it is likely that the combination of BFR and HIIT promotes localized adaptations within the peripheral muscle tissues performing the exercise and then being subjected to BFR i.e. in the case of cycling, the quadriceps muscle group. Such adaptations are coordinated by the metabolic changes known to occur with both exercise and localized ischaemia. These result in an increased expression of several intracellular transcription factors, which subsequently orchestrate a cascade of downstream signalling pathways that promote physiological adaptations within skeletal muscle. These adaptations include increased capillarisation (angiogenesis), mitochondrial biogenesis, and a phenotypic switch towards predominantly slow-oxidative non-fatiguing type 1 muscle fibres. There has also been the suggestion that BFR can upregulate peripheral vascular adaptations. Collectively, these increase muscle oxygen delivery (̇Q̇mO2) and uptake (V̇mO2), both of which are now considered as crucial training-induced adaptive responses for increasing whole-body V̇O2peak and ameliorating exercise intolerance symptoms in CHF patients.
Indeed, several exercise training interventions in CHF patients have previously focused on promoting adaptive responses within the vasculature and peripheral skeletal muscles as a means of increasing V̇O2peak. The rationale for these studies is based on the poor correlation between LV ejection fraction and exercise intolerance symptoms in CHF. Furthermore, it is now well recognised that several peripheral impairments within the skeletal muscle system contribute to the symptoms of exercise intolerance in CHF. These include vascular dysfunction, muscle fibre atrophy, reduced capillarisation, mitochondrial dysfunction, and a shift towards predominantly fast-twitch glycolytic type IIx fibres. Collectively, these contribute to poor symptoms and therefore previous exercise training interventions in CHF patients have focused on promoting adaptations within the periphery as a means of increasing V̇O2peak and ameliorating exercise intolerance. Many of these studies have successfully demonstrated an increase in V̇O2peak primarily by promoting adaptations within the periphery. As such, we believe that BFR+HIIT represents a novel training stimulus that may promote adaptive responses within the vascular and skeletal muscle systems that are likely to have significant effects in terms of increasing V̇O2peak, ameliorating exercise intolerance and improving quality of life in CHF patients.
- Conditions
- Chronic Heart Failure
- Being tested
- Blood flow restriction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood flow restrictionDevice
Occlusion of venous flow between bouts of HIIT training exercise
| Study group | Role | What they receive |
|---|---|---|
| Blood flow restriction | Active comparator | Not described Receives: Device: Blood flow restriction |
| Usual training | Sham comparator | Not described Receives: Device: Blood flow restriction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak oxygen consumption (ml.kg.min)
Peak oxygen consumption
Measured: 4 weeks
Secondary outcomes (1)
Quality of life (points)
Minnesota Living with Heart Failure Questionnaire
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start10 Mar 2018
- Primary completion1 Jan 2021
- Study completion1 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Heart FailureStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, KK Witte, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03342833
- Sponsor's protocol ID
- 17.YH.0348
- Acronym
- BFR-CHF
- Status last verified
- Apr 2021
- First submitted
- 7 Nov 2017
- Last updated
- 30 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Flow Restriction Training in Chronic Heart Failure: an Effective Training Strategy?
- ClinicalTrials.gov ID
- NCT03342833
- Acronym / sponsor ID
- BFR-CHF / 17.YH.0348
- Conditions
- Chronic Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Study start
- 10 Mar 2018 (actual)
- Primary completion
- 1 Jan 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 17 Nov 2017 (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 purpose of this current study proposal is to identify the potential physiological adaptations arising from a combined BFR+HIIT training intervention in CHF patients. We hypothesise that the addition of BFR to HIIT will increase whole-body V̇O2peak by promoting vascular and skeletal muscle adaptations above that seen with HIIT alone. The secondary outcomes of this study are to determine if such a training intervention leads to clinical improvements in exercise intolerance symptoms and quality of life indices. Given that the majority of previous research in to both BFR and HIIT has largely involved young, healthy and relatively active participants, the final objective of this current proposal is to determine the viability, tolerability and efficacy of these training modalities in an elderly cohort of predominantly sedentary CHF patients.
Detailed description
Exercise training in CHF is a potentially effective intervention for improving symptomatic and prognostic outcomes, but remains underutilised in contemporary CHF management in the United Kingdom. This underutilisation may be partly the result of multiple approaches to training but also due to inconsistent and overall modest results of any of the interventions on important patient-orientated outcomes. A key consideration in this latter regard is whether disease related symptoms (e.g. dyspnoea) during exercise training limit the physiological work achievable during training, limiting the degree of the training stimulus to below the level at which physiological adaptation can be achieved. For example, in COPD participants only those in whom skeletal muscle fatigue was present after a training session evidenced any improvement in functional exercise capacity and health-related quality of life following a 3-month rehabilitation programme. Investigating novel approaches to training that promote greater gains in training effect may therefore lead to greater changes in patient-centred outcomes which will eventually stimulate greater uptake and alleviate the clinical burden chronic heart failure.
Blood Flow Restriction (BFR) training is a novel strategy in which a pressure cuff is inflated around the proximal portion of the exercising limbs (e.g. at the top of the arms or legs) during exercise or in recovery periods between exercise bouts. The pressure of the cuff is set to allow arterial blood flow but occlude venous return, subsequently altering (or maintaining) the local metabolic milieu, resulting in upregulation of several downstream pathways that augment the adaptive response to exercise. BFR has been successfully employed previously in combination with resistance exercise (RE) training to augment skeletal muscle hypertrophy in isolated peripheral muscles. Importantly, this training has been shown to promote muscle hypertrophy with concomitant increases in isokinetic strength in elderly individuals performing at low exercise work rates. This therefore demonstrates that BFR can induce comparatively similar adaptations at a lower power in elderly populations, suggesting this training strategy may have applications in other groups, such as CHF patients.
Additional studies have also demonstrated improvements in V̇O2peak by combining BFR with traditional low-intensity endurance training or high-intensity interval training (HIIT). Using a within-measures design, the first of these studies demonstrated that a 4-week training intervention (4 sessions per week) of 45-mins single-leg cycling under ischaemic conditions (induced by an external pressure of 50 mmHg in a pressure chamber) improved time-to-fatigue and V̇O2peak significantly more than an identical training intervention on the contralateral leg under normoxic (non-ischaemic) conditions. Further research with a between-measures design showed that 8-weeks of low-intensity cycling (40% V̇O2peak) with continuous BFR (160-210 mmHg) can increase both muscle strength and cross-sectional area as well as V̇O2peak significantly more than a control intervention using the same protocol without BFR. Interestingly, the control group exercised for longer during their training sessions (45-mins vs 15-mins for BFR) demonstrating that BFR not only has the potential to augment adaptations but is also a time-efficient modality of exercise. Given that lack of time is frequently cited as a barrier to regular exercise training, novel training interventions, such as BFR, that aren't time-consuming may be considered an attractive alternative form of exercise.
HIIT is also promoted as a time-efficient training modality that is known to promote comparable physiological adaptations to traditional high-volume low-intensity endurance exercise training. HIIT typically involves repeated bouts of intense ('near-maximal') exercise separated by brief periods of recovery. Some training studies have now combined BFR with HIIT (BFR+HIIT), applying the pressure cuff during recovery periods rather than during exercise. This combination of BFR+HIIT allows the working muscle to perform as normal during the short bouts of exercise; however, application of the cuff during recovery was shown to promote superior physiological adaptations above HIIT alone. Specifically, this study demonstrated that 4-weeks (2 sessions per week) of sprint interval training (4-7 bouts of maximal 30s cycling sprints with 4.5-mins recovery) combined with BFR (2-mins at 130 mmHg during the recovery period) significantly increased V̇O2peak compared to a control group performing the same training protocol without BFR.
Although the exact mechanisms responsible for this superior physiological response have yet to be fully elucidated, it is likely that the combination of BFR and HIIT promotes localized adaptations within the peripheral muscle tissues performing the exercise and then being subjected to BFR i.e. in the case of cycling, the quadriceps muscle group. Such adaptations are coordinated by the metabolic changes known to occur with both exercise and localized ischaemia. These result in an increased expression of several intracellular transcription factors, which subsequently orchestrate a cascade of downstream signalling pathways that promote physiological adaptations within skeletal muscle. These adaptations include increased capillarisation (angiogenesis), mitochondrial biogenesis, and a phenotypic switch towards predominantly slow-oxidative non-fatiguing type 1 muscle fibres. There has also been the suggestion that BFR can upregulate peripheral vascular adaptations. Collectively, these increase muscle oxygen delivery (̇Q̇mO2) and uptake (V̇mO2), both of which are now considered as crucial training-induced adaptive responses for increasing whole-body V̇O2peak and ameliorating exercise intolerance symptoms in CHF patients.
Indeed, several exercise training interventions in CHF patients have previously focused on promoting adaptive responses within the vasculature and peripheral skeletal muscles as a means of increasing V̇O2peak. The rationale for these studies is based on the poor correlation between LV ejection fraction and exercise intolerance symptoms in CHF. Furthermore, it is now well recognised that several peripheral impairments within the skeletal muscle system contribute to the symptoms of exercise intolerance in CHF. These include vascular dysfunction, muscle fibre atrophy, reduced capillarisation, mitochondrial dysfunction, and a shift towards predominantly fast-twitch glycolytic type IIx fibres. Collectively, these contribute to poor symptoms and therefore previous exercise training interventions in CHF patients have focused on promoting adaptations within the periphery as a means of increasing V̇O2peak and ameliorating exercise intolerance. Many of these studies have successfully demonstrated an increase in V̇O2peak primarily by promoting adaptations within the periphery. As such, we believe that BFR+HIIT represents a novel training stimulus that may promote adaptive responses within the vascular and skeletal muscle systems that are likely to have significant effects in terms of increasing V̇O2peak, ameliorating exercise intolerance and improving quality of life in CHF patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Blood flow restriction | Active comparator | Device: Blood flow restriction |
| Usual training | Sham comparator | Device: Blood flow restriction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with New York Heart Association (NYHA) class II-III symptoms Stable CHF of at least 3 months duration On optimally tolerated medication for CHF No contraindications for cycling exercise Able and willing to give informed consent
Key exclusion criteria (1 listed)
- Class IV CHF Any contraindications to exercise Significant COPD (FEV1<60%), severe renal disease (eGFR<30), primary pulmonary hypertension as a co-morbidity Unable to give informed consent Current diagnosis of active cancer, inflammatory or musculoskeletal disease (e.g. rheumatoid arthritis), on-going infection or sepsis.
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 |
|---|---|---|
| Blood flow restrictionOcclusion of venous flow between bouts of HIIT training exercise | Device | Blood flow restriction, Usual training |
Primary outcome
Peak oxygen consumption (ml.kg.min)
Time frame: 4 weeks
Peak oxygen consumption
1 secondary outcome
Quality of life (points)
Time frame: 4 weeks
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 30 Apr 2021.
- Individual participant dataSharing planned: Yes
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Blood flow restriction in people with Chronic Heart Failure, run by University of Leeds at 1 site in United Kingdom.
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 1 inclusion and 1 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 30 Apr 2021. 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 United Kingdom. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Peak oxygen consumption (ml.kg.min) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2021.