Peripheral Arterial DiseasePhase 2NCT02636283
Use of Entresto Sacubitril/Valsartan for the Treatment of Peripheral Arterial Disease
A Phase 2 study testing Entresto in people with Peripheral Arterial Disease, run by University of Minnesota at 1 site in United States.
Trial summary
This study proposes the use of Entresto (sacubitril/valsartan) to test the effects on pain free walking duration on patients with peripheral arterial disease, a condition caused by decreased blood flow to the muscles in the legs. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Entresto
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2017to 1 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject with symptoms of intermittent claudication, such as exercise-induced pain, cramps, fatigue, or other equivalent discomfort, involving large muscle groups of the leg(s) (calf, thigh, buttocks), relieved by rest.
- Ankle-brachial index ≤ 0.90 acquired according to the American Heart Association guidelines.
- Highest ankle pressure reduced by at least 25 mm Hg after exercise compared to resting pressure (or loss of previously present Doppler signal for both the posterior tibial and anterior tibial arteries immediately after exercise if arteries were incompressible).
- Patients on medical treatment for PAD without significant improvement in intermittent claudication within the last 6 months.
Who cannot join
- Age < 18 and > 80 years.
- Patients with physician diagnosed chronic kidney disease or heart failure stage II or IV or unstable angina.
- Echocardiographic evidence of cardiomyopathies and pulmonary hypertension.
- Patients that have received cancer treatment within the last year (except skin cancer).
- Severe limitations in mobility due to osteomuscular disorders present at time of interview.
- Dementia or other mental disorders that prevent patients from following a research protocol present at time of interview
Show all 9Show fewer
- Patients engaged in an exercise rehabilitation program within the past 6 months.
- Patients schedule to undergo an arterial revascularization procedure during the study or have undergone one within the past 6 months.
- Inconsistent maximal walking distance on the treadmill test.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
About this study
Official title: Use of Entresto (Sacubitril/Valsartan) for the Treatment of Peripheral Arterial Disease
This study proposes the use of Entresto (sacubitril/valsartan) to test the effects on pain free walking duration on patients with peripheral arterial disease, a condition caused by decreased blood flow to the muscles in the legs.
Read the detailed description
Current approaches for the treatment of peripheral arterial disease (PAD) lack the success observed in the treatment of other forms of vascular diseases. A potential reason for this may be that available treatments do not target the pathological mechanisms implicated in the development of PAD. These mechanisms include obstruction of aortic-iliac arteries and its branches due to the formation of atherosclerotic plaques and mitochondrial and microvascular dysfunction. Although blood flow improves following surgical revascularization, pain free and maximal walking duration does not improve to the same degree. This suggests that in addition to blood flow obstruction, mitochondrial and microvascular dysfunction are significant factors implicated in the development of PAD.
Therefore, any treatment designed for patients with PAD should be aimed at improving mitochondrial and microvascular function. In this regard, natriuretic peptides (NP) have been shown to increase mitochondrial and microvascular density and these two findings have been associated with increases in oxygen consumption and perfusion of skeletal muscles.
The Investigator proposes that an increase in endogenous natriuretic peptides by inhibiting the enzyme that degrades it in blood will increase mitochondrial and microvascular function and this will be associated with an increase in maximal and pain free walking duration. To test this hypothesis the investigators have designed a double blind randomized controlled clinical trial providing sacubitril/valsartan for 12 weeks trial period.The improvements in mitochondrial and microvascular function will be measured using magnetic resonance (MR) spectroscopy and functional MR imaging and an exercise stress test will be used to assess maximal and pain free walking duration. This trial will provide patients with PAD with a non-surgical, cause-specific treatment option.
- Conditions
- Peripheral Arterial Disease
- Being tested
- Entresto, Placebo group
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntrestoDrug
Oral pills
Placebo groupDrug
The placebo pills
| Study group | Role | What they receive |
|---|---|---|
| Entresto | Active comparator | oral route Receives: Drug: Entresto |
| Placebo group | Placebo comparator | Oral placebo Receives: Drug: Placebo group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treadmill Walk Until Pain Initiated in Minutes
Time in minutes on a standardized treadmill test to initiation of pain and time until pain requires patient to stop walking
Measured: 12 weeks
Secondary outcomes (4)
Mitochondrial and Microvascular Function Arterial Elasticity
Post-contraction measures of mitochondrial and microvascular function using MR spectroscopy and functional MRI
Measured: 12 weeks
Insulin Sensitivity
Using Homeostasis Model Assessment (HOMA) index
Measured: 12 weeks
Arterial Elasticity
Pulse wave pressure analysis
Measured: 12 weeks
Quality of Life Questionnaires
Questionnaires describing independent living and quality of life
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2015 (estimated)
- Study start31 Dec 2017
- Primary completion1 Nov 2018
- Study completion1 Nov 2018
Why it stopped: Recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- 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, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Sponsor
- Investigators
- Otto A Sanchez, M.D., Ph.D., Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02636283
- Sponsor's protocol ID
- 15SDG25360025
- Status last verified
- Dec 2019
- First submitted
- 29 Oct 2015
- Last updated
- 17 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Entresto (Sacubitril/Valsartan) for the Treatment of Peripheral Arterial Disease
- ClinicalTrials.gov ID
- NCT02636283
- Acronym / sponsor ID
- 15SDG25360025
- Conditions
- Peripheral Arterial Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- 31 Dec 2017 (actual)
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 21 Dec 2015 (estimated)
- Results
- Posted 17 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study proposes the use of Entresto (sacubitril/valsartan) to test the effects on pain free walking duration on patients with peripheral arterial disease, a condition caused by decreased blood flow to the muscles in the legs.
Detailed description
Current approaches for the treatment of peripheral arterial disease (PAD) lack the success observed in the treatment of other forms of vascular diseases. A potential reason for this may be that available treatments do not target the pathological mechanisms implicated in the development of PAD. These mechanisms include obstruction of aortic-iliac arteries and its branches due to the formation of atherosclerotic plaques and mitochondrial and microvascular dysfunction. Although blood flow improves following surgical revascularization, pain free and maximal walking duration does not improve to the same degree. This suggests that in addition to blood flow obstruction, mitochondrial and microvascular dysfunction are significant factors implicated in the development of PAD.
Therefore, any treatment designed for patients with PAD should be aimed at improving mitochondrial and microvascular function. In this regard, natriuretic peptides (NP) have been shown to increase mitochondrial and microvascular density and these two findings have been associated with increases in oxygen consumption and perfusion of skeletal muscles.
The Investigator proposes that an increase in endogenous natriuretic peptides by inhibiting the enzyme that degrades it in blood will increase mitochondrial and microvascular function and this will be associated with an increase in maximal and pain free walking duration. To test this hypothesis the investigators have designed a double blind randomized controlled clinical trial providing sacubitril/valsartan for 12 weeks trial period.The improvements in mitochondrial and microvascular function will be measured using magnetic resonance (MR) spectroscopy and functional MR imaging and an exercise stress test will be used to assess maximal and pain free walking duration. This trial will provide patients with PAD with a non-surgical, cause-specific treatment option.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Entresto | Active comparator | Drug: Entrestooral route |
| Placebo group | Placebo comparator | Drug: Placebo groupOral placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subject with symptoms of intermittent claudication, such as exercise-induced pain, cramps, fatigue, or other equivalent discomfort, involving large muscle groups of the leg(s) (calf, thigh, buttocks), relieved by rest.
- Ankle-brachial index ≤ 0.90 acquired according to the American Heart Association guidelines.
- Highest ankle pressure reduced by at least 25 mm Hg after exercise compared to resting pressure (or loss of previously present Doppler signal for both the posterior tibial and anterior tibial arteries immediately after exercise if arteries were incompressible).
- Patients on medical treatment for PAD without significant improvement in intermittent claudication within the last 6 months.
Key exclusion criteria (9 listed)
- Age < 18 and > 80 years.
- Patients with physician diagnosed chronic kidney disease or heart failure stage II or IV or unstable angina.
- Echocardiographic evidence of cardiomyopathies and pulmonary hypertension.
- Patients that have received cancer treatment within the last year (except skin cancer).
- Severe limitations in mobility due to osteomuscular disorders present at time of interview.
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 |
|---|---|---|
| EntrestoOral pills | Drug | Entresto |
| Placebo groupThe placebo pills | Drug | Placebo group |
Primary outcome
Treadmill Walk Until Pain Initiated in Minutes
Time frame: 12 weeks
Time in minutes on a standardized treadmill test to initiation of pain and time until pain requires patient to stop walking
4 secondary outcomes
Mitochondrial and Microvascular Function Arterial Elasticity
Time frame: 12 weeks
Insulin Sensitivity
Time frame: 12 weeks
Arterial Elasticity
Time frame: 12 weeks
Quality of Life Questionnaires
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Otto A Sanchez, M.D., Ph.D. principal investigator
University of Minnesota
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 Entresto in people with Peripheral Arterial Disease, run by University of Minnesota at 1 site in United States.
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 4 inclusion and 9 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: stopped early, as of the sponsor's last update on 17 Dec 2019. 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 States. 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?
Yes. Results are posted in the registry (first posted 17 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Treadmill Walk Until Pain Initiated in Minutes (time frame: 12 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 17 Dec 2019.