Chronic Heart FailurePhase 2NCT03159988
Angiotensin (1-7) Treatment to Improve Cognitive Functioning in Heart Failure Patients
A Phase 2 study testing Angiotensin-(1-7) and Memory Training in people with Chronic Heart Failure and Cognitive Impairment, run by University of Arizona at 1 site in United States.
Trial summary
Heart failure (HF) is the major cardiovascular disease that continues to grow in prevalence, largely due to aging of the population. HF is described as the inability of the heart to keep up with the demands on it and, specifically, failure of the heart to pump blood with normal efficiency. Read more about this study
- Who is it for?
- Ages 55 to 75 years
- Conditions the study is for
- Chronic Heart Failure, Cognitive Impairment
- What is being tested?
- Angiotensin-(1-7) and Memory Training
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to 1 Jun 2026
- 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 55 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with chronic HF ≥ 90 days prior to enrollment
- Be clinically stable and on stable medications
- Stable NYHA Class II-III HF or symptoms during mild or moderate exercise but not at rest (i.e. shortness of breath)
- Fluent in English or formal education in English starting from at least the age of 5
- Able and willing to provide informed consent
Who cannot join
- Evidence of decompensated HF
- Symptoms or signs of active coronary ischemia
- Criteria for DSM-IV diagnosis or history of serious psychiatric disease, or diagnosed learning disabilities. May have psychological problem that has been well controlled on medication for a sustained period of more than 2 years.
- Any other neurological, psychiatric, or medical illness or injury expected to interfere with cognitive function or memory including but not limited to stroke (diagnosed with evidence of stroke), head injury, epilepsy, Alzheimer's, Parkinson's, brain cancer, depression (current, but ok in past). Migraines OK. May have TIAs with no sign of impairment and no sequelae following the event
- Active substance abuse disorder i.e. alcohol, nicotine. Previous substance abuse of cocaine, Ecstasy, LSD, IV drugs
- History of seizure disorder as child or currently experiencing or on medications for seizures. Exception is febrile seizures as a child.
Show all 12Show fewer
- Any condition which may prevent the subject from adhering to the study protocol, as determined by the Investigator i.e. reported learning disability, cataracts impairing vision, colorblindness.
- Movement disorders that prevent the subject from being still for the MRI
- The presence of any metallic implant or foreign body, including dental bridges excludes patients from MRI. Removable body piercings/implants okay. Patients with a metal implant or foreign body will still be enrolled; however these patients will not undergo MRI testing.
- Professional metalworker or welder
- Recurring panic attacks or claustrophobic
- Abnormally high weight or height to fit in scanner (Bore 70cm)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arizona Sarver Heart Center
Tucson, Arizona, 85724-5046
About this study
Heart failure (HF) is the major cardiovascular disease that continues to grow in prevalence, largely due to aging of the population. HF is described as the inability of the heart to keep up with the demands on it and, specifically, failure of the heart to pump blood with normal efficiency. Cognitive impairment (CI) is common in HF patients, resulting in a person having trouble remembering, learning new things, concentrating, or making decisions that affect their everyday life. Patients with HF have been show repeatedly to have trouble remembering and learning new things when compared to the general population. Patients with demonstrated CI have a significantly increased risk of developing dementia (memory loss). It is believed that the reason HF patients have a higher risk of CI is possibly due to less blood reaching the brain and an overall inflammatory process occurring in the body including the brain. To date there are no known therapies that can help treat CI caused by HF.
A substance, Angiotensin-(1-7) [Ang-(1-7)], is known to decrease inflammation in the brain. Early studies in humans have shown it to be safe. This substance is naturally produced in the body and works by activating areas in the brain involved in memory. Investigators believe that Ang-(1-7) may be able to help lower the risk of loss of cognitive function in patients with heart failure.
In this study, we will try to determine whether Ang-(1-7) is a safe and effective treatment for cognitive impairment in HF patients.
Read the detailed description
In this non-randomized pilot study 16 heart failure patients will be enrolled. Adults (ages 55-75) with chronic HF will be recruited who do not have neurologic or psychiatric disorders expected to interfere with memory function. Patients must have been diagnosed with HF ≥ 90 days prior to enrollment, be clinically stable, and on stable medications. Participants have a medical history and examination, with documentation of evidence of HF, and screening to rule out dementia (Mini-Mental State Exam score less than 25), and depression (Geriatric Depression Scale score greater than 10. Participants will be treated for 12 weeks with a daily dose of subcutaneous Ang-(1-7) (100 mcg/kg/day). Half of the group will be given memory training in 2-hr sessions twice weekly for two weeks beginning at 6 weeks of drug treatment. Prior to drug treatment, baseline measures will include memory and neuropsychological tests and inflammatory markers. Memory and neuropsychological tests will be repeated at 3 weeks, 6 weeks and 12 weeks. Inflammatory biomarkers will be reassessed at 6 weeks and 12 weeks. Blood draws for pharmacokinetic (PK) measurements will be obtained at baseline and Day 7. MRI scans will be obtained from all participants who do not have an ICD, pacemaker or other contraindication to MRI at baseline with repeat scans at 12 weeks. Lastly Self-Care Efficacy testing will be obtained at 12 weeks from all participants.
Aim 1 Primary Outcome: Changes in performance on the Memory Intentions Test (MIST, a test of PM) between baseline and 12 weeks27 will be the primary endpoint to test effectiveness of PMT in the presence or absence of Ang-(1-7) treatment.MIST scores have been shown to predict medication adherence.
Aim 1 Secondary Outcomes:
- Safety of the treatment will be assessed by careful collection of standard serious adverse events, and comparison of events across treatment arms. In addition, patients will be asked about difficulties associated with the therapy, and medication vials collected to assess compliance with therapy.
- Self-care efficacy at 12 weeks will be measured using the SCHFI, a validated tool.
- Other neuropsychological measures of memory, executive functions, and psychomotor speed will be assessed at baseline, 3 weeks, 6 weeks, and at the 12 week follow-up.
- HF quality of life will be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12 weeks.
- Adjudicated HF hospitalizations, all-cause hospitalizations and death will be assessed by treatment arm.
Aim 2: Systemic Inflammation Assay: At baseline, and after 6 and 12 weeks of Ang-(1-7) treatment, blood will be collected for assessment of systemic inflammation. Blood will be placed in lavender-top EDTA tubes, centrifuged to obtain plasma, and rapidly frozen in liquid nitrogen.
Cytokines, chemokines, and additional circulating inflammatory analytes will be detected and quantified by multiplex immunoassay using a MAGPIX®. Each sample will be measured in duplicate. Data will be analyzed by ANOVA across all groups.
Aim 2 Primary Outcome: Immunosuppressive cytokines TGFα and IL-1 will be measured as they play an important role in the anti-inflammatory actions of Ang-(1-7) and are widely used as functional indicators of systemic inflammation. The more common clinical inflammatory marker of systemic inflammation C-reactive protein, will also be measured.
- Conditions
- Chronic Heart Failure, Cognitive Impairment
- Being tested
- Angiotensin-(1-7), Memory Training
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin-(1-7)Drug
Angiotensin-(1-7) 100mcg/kg/day for 12 weeks
Memory TrainingBehavioural
50% of the treatment arm will receive 2 session per week for 2 weeks of memory training
| Study group | Role | What they receive |
|---|---|---|
| Non-randomized treatment group | Experimental | 12 weeks of daily does subcutaneous injection of Angiotensin-(1-7) 100 mcg/kg/day Receives: Drug: Angiotensin-(1-7); Behavioral: Memory Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in performance on the Memory Intentions Test (MIST)
MIST will be performed at baseline and 12 weeks to test prospective memory
Measured: Baseline and 12 weeks
Secondary outcomes (2)
Assessment of self-reported Quality of Life (QoL)
Assessment of QoL will be performed at baseline and 12 weeks utilizing the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Measured: Baseline and 12 weeks
Systemic Inflammation Assay
Assessment of systemic inflammation will be performed using plasma samples at 6 weeks and 12 weeks
Measured: 6 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2017
- Study startApr 2016
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Why it stopped: Study Suspended. Slow enrollment.
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.
- More trials run by University of ArizonaThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meredith Hay, University of Arizona
- Investigators
- Nancy K Sweitzer, MD, PhD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03159988
- Sponsor's protocol ID
- 1510150837
- Status last verified
- May 2023
- First submitted
- 23 Oct 2016
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin (1-7) Treatment to Improve Cognitive Functioning in Heart Failure Patients
- ClinicalTrials.gov ID
- NCT03159988
- Acronym / sponsor ID
- 1510150837
- Conditions
- Chronic Heart Failure, Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Study Suspended. Slow enrollment.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 19 May 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.
Heart failure (HF) is the major cardiovascular disease that continues to grow in prevalence, largely due to aging of the population. HF is described as the inability of the heart to keep up with the demands on it and, specifically, failure of the heart to pump blood with normal efficiency. Cognitive impairment (CI) is common in HF patients, resulting in a person having trouble remembering, learning new things, concentrating, or making decisions that affect their everyday life. Patients with HF have been show repeatedly to have trouble remembering and learning new things when compared to the general population. Patients with demonstrated CI have a significantly increased risk of developing dementia (memory loss). It is believed that the reason HF patients have a higher risk of CI is possibly due to less blood reaching the brain and an overall inflammatory process occurring in the body including the brain. To date there are no known therapies that can help treat CI caused by HF.
A substance, Angiotensin-(1-7) [Ang-(1-7)], is known to decrease inflammation in the brain. Early studies in humans have shown it to be safe. This substance is naturally produced in the body and works by activating areas in the brain involved in memory. Investigators believe that Ang-(1-7) may be able to help lower the risk of loss of cognitive function in patients with heart failure.
In this study, we will try to determine whether Ang-(1-7) is a safe and effective treatment for cognitive impairment in HF patients.
Detailed description
In this non-randomized pilot study 16 heart failure patients will be enrolled. Adults (ages 55-75) with chronic HF will be recruited who do not have neurologic or psychiatric disorders expected to interfere with memory function. Patients must have been diagnosed with HF ≥ 90 days prior to enrollment, be clinically stable, and on stable medications. Participants have a medical history and examination, with documentation of evidence of HF, and screening to rule out dementia (Mini-Mental State Exam score less than 25), and depression (Geriatric Depression Scale score greater than 10. Participants will be treated for 12 weeks with a daily dose of subcutaneous Ang-(1-7) (100 mcg/kg/day). Half of the group will be given memory training in 2-hr sessions twice weekly for two weeks beginning at 6 weeks of drug treatment. Prior to drug treatment, baseline measures will include memory and neuropsychological tests and inflammatory markers. Memory and neuropsychological tests will be repeated at 3 weeks, 6 weeks and 12 weeks. Inflammatory biomarkers will be reassessed at 6 weeks and 12 weeks. Blood draws for pharmacokinetic (PK) measurements will be obtained at baseline and Day 7. MRI scans will be obtained from all participants who do not have an ICD, pacemaker or other contraindication to MRI at baseline with repeat scans at 12 weeks. Lastly Self-Care Efficacy testing will be obtained at 12 weeks from all participants.
Aim 1 Primary Outcome: Changes in performance on the Memory Intentions Test (MIST, a test of PM) between baseline and 12 weeks27 will be the primary endpoint to test effectiveness of PMT in the presence or absence of Ang-(1-7) treatment.MIST scores have been shown to predict medication adherence.
Aim 1 Secondary Outcomes:
- Safety of the treatment will be assessed by careful collection of standard serious adverse events, and comparison of events across treatment arms. In addition, patients will be asked about difficulties associated with the therapy, and medication vials collected to assess compliance with therapy.
- Self-care efficacy at 12 weeks will be measured using the SCHFI, a validated tool.
- Other neuropsychological measures of memory, executive functions, and psychomotor speed will be assessed at baseline, 3 weeks, 6 weeks, and at the 12 week follow-up.
- HF quality of life will be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12 weeks.
- Adjudicated HF hospitalizations, all-cause hospitalizations and death will be assessed by treatment arm.
Aim 2: Systemic Inflammation Assay: At baseline, and after 6 and 12 weeks of Ang-(1-7) treatment, blood will be collected for assessment of systemic inflammation. Blood will be placed in lavender-top EDTA tubes, centrifuged to obtain plasma, and rapidly frozen in liquid nitrogen.
Cytokines, chemokines, and additional circulating inflammatory analytes will be detected and quantified by multiplex immunoassay using a MAGPIX®. Each sample will be measured in duplicate. Data will be analyzed by ANOVA across all groups.
Aim 2 Primary Outcome: Immunosuppressive cytokines TGFα and IL-1 will be measured as they play an important role in the anti-inflammatory actions of Ang-(1-7) and are widely used as functional indicators of systemic inflammation. The more common clinical inflammatory marker of systemic inflammation C-reactive protein, will also be measured.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Non-randomized treatment group | Experimental | Drug: Angiotensin-(1-7), Behavioral: Memory Training12 weeks of daily does subcutaneous injection of Angiotensin-(1-7) 100 mcg/kg/day |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosed with chronic HF ≥ 90 days prior to enrollment
- Be clinically stable and on stable medications
- Stable NYHA Class II-III HF or symptoms during mild or moderate exercise but not at rest (i.e. shortness of breath)
- Fluent in English or formal education in English starting from at least the age of 5
- Able and willing to provide informed consent
Key exclusion criteria (12 listed)
- Evidence of decompensated HF
- Symptoms or signs of active coronary ischemia
- Criteria for DSM-IV diagnosis or history of serious psychiatric disease, or diagnosed learning disabilities. May have psychological problem that has been well controlled on medication for a sustained period of more than 2 years.
- Any other neurological, psychiatric, or medical illness or injury expected to interfere with cognitive function or memory including but not limited to stroke (diagnosed with evidence of stroke), head injury, epilepsy, Alzheimer's, Parkinson's, brain cancer, depression (current, but ok in past). Migraines OK. May have TIAs with no sign of impairment and no sequelae following the event
- Active substance abuse disorder i.e. alcohol, nicotine. Previous substance abuse of cocaine, Ecstasy, LSD, IV drugs
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 |
|---|---|---|
| Angiotensin-(1-7)Angiotensin-(1-7) 100mcg/kg/day for 12 weeks | Drug | Non-randomized treatment group |
| Memory Training50% of the treatment arm will receive 2 session per week for 2 weeks of memory training | Behavioural | Non-randomized treatment group |
Primary outcome
Changes in performance on the Memory Intentions Test (MIST)
Time frame: Baseline and 12 weeks
MIST will be performed at baseline and 12 weeks to test prospective memory
2 secondary outcomes
Assessment of self-reported Quality of Life (QoL)
Time frame: Baseline and 12 weeks
Systemic Inflammation Assay
Time frame: 6 weeks and 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Individual participant dataSharing planned: Undecided
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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.
Nancy K Sweitzer, MD, PhD principal investigator
University of Arizona
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 Angiotensin-(1-7) and Memory Training in people with Chronic Heart Failure and Cognitive Impairment, run by University of Arizona 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 5 inclusion and 12 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: paused, as of the sponsor's last update on 4 Jun 2025. 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. 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?
Results are not available in the source record.
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?
Changes in performance on the Memory Intentions Test (MIST) (time frame: Baseline and 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 4 Jun 2025.