Biomarker Study: Heart Failure Patients at Risk

Summary

In order to determine if NfL can be a prognostic biomarker for VCID, participants will undergo a baseline evaluation consisting of neuropsychological testing and a blood draw with a 12-month follow-up consisting of neuropsychological testing and blood draw. After indicated interest in the study, participants will be screened either in person during a regularly scheduled clinic visit or by phone for eligibility. After consenting, participants will be scheduled for a baseline testing session. One session, lasting about 3 hrs, will include neuropsychological testing and a blood draw. After completion of baseline testing, participants who agree to take part in the clinical trial will begin a 12-week treatment of Ang-(1-7) via daily subcutaneous injections. During the drug treatment, participants will be called weekly to ensure that everything is going well with the injections. After participants have completed the 12-week injection period, participants will be scheduled for a second appointment which will include a blood draw and neuropsychological testing. All participant will be scheduled for a 12-month follow-up, which will include a blood draw and neuropsychological testing. Participants will be called every second month by research staff for a brief update on changes to health status, and to increase compliance with the 12-month follow-up.

Our One-Year outcome for this study is to provide early proof-of-concept clinical trial data that will support a larger, more comprehensive NIH funded study on the safety and efficacy of Ang-(1-7) to prevent cognitive impairment in HF patients at risk for developing VCID/ADRD. Our Long-Term outcome is to demonstrate whether plasma NfL exhibits characteristics making it useful as a Prognostic Biomarker to predict cognitive decline in early heart disease-associated VCID and identify pre VCID-symptomatic in individuals with symptomatic HF. Our goal will be to use levels of plasma Nfl as an enrollment enrichment factor in future trials to allow enrollment or stratification of patients more likely to develop VCID or ADRD and be responsive to Ang-(1-7) therapy.

Conditions

• Heart Failure NYHA Class II
• Heart Failure NYHA Class III
• Heart Failure NYHA Class IV

Interventions

DRUG

Angiotensin 1-7

A substance, Angiotensin-(1-7) \[Ang-(1-7)\], is known to decrease inflammation in the brain. This substance is naturally produced in the body and works by activating areas in the brain involved in memory. Previous studies examining the ability of Ang-(1-7) treatment to prevent memory loss post open-heart surgery found that 21 days of treatment with Ang-(1-7) protected memory post-surgery. Participants treated with Ang-(1-7) were protected from post-surgery increase in NfL levels. This clinical "sub-project" within the existing study will allow us to obtain preliminary data to evaluate the safety and efficacy of treatment with Ang-(1-7) to improve cognitive function and determine if this treatment is associated with changes in plasma levels of NfL protein.30 participants will take 100 micrograms of Ang-(1-7) per day via subcutaneous injection for 90 days.

DRUG

Saline solution

Saline solution will be given as a placebo intervention to 10 participants. These participants will take 100 micrograms of saline solution per day via subcutaneous injection for 90 days.

Sponsors & Collaborators

• University of Arizona

  lead OTHER

Principal Investigators

• Lee Ryan, Ph.D. · University of Arizona

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-04-30

Primary Completion

2023-12-31

Completion

2023-12-31

FDA Drug

Yes

Countries

• United States

Study Locations