Angiotensin (1-7) Treatment to Improve Cognitive Functioning in Heart Failure Patients

NCT03159988 | Suspended Phase 2 DMC

• 1 other identifier: 1510150837
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Heart Failure; Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Changes in performance on the Memory Intentions Test (MIST)

  MIST will be performed at baseline and 12 weeks to test prospective memory

  Baseline and 12 weeks

Secondary Outcomes (2)

• Assessment of self-reported Quality of Life (QoL)

  Baseline and 12 weeks

• Systemic Inflammation Assay

  6 weeks and 12 weeks

Study Arms (1)

Non-randomized treatment group

EXPERIMENTAL

12 weeks of daily does subcutaneous injection of Angiotensin-(1-7) 100 mcg/kg/day

Drug: Angiotensin-(1-7); Behavioral: Memory Training

Interventions

Angiotensin-(1-7) DRUG

Angiotensin-(1-7) 100mcg/kg/day for 12 weeks

Non-randomized treatment group

Memory Training BEHAVIORAL

50% of the treatment arm will receive 2 session per week for 2 weeks of memory training

Non-randomized treatment group

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona Sarver Heart Center

Tucson, Arizona, 85724-5046, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

angiotensin I (1-7); Cognitive Training

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Nancy K Sweitzer, MD, PhD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, University of Arizona College of Medicine Department of Physiology and Department of Psychology; Evelyn F. McKnight Brain Institute, Sarver Heart Center University of Arizona

Study Record Dates

• First Submitted: October 23, 2016
• First Posted: May 19, 2017
• Study Start: April 1, 2016
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 4, 2025

Record last verified: 2023-05

Locations

US (1)