NCT05336175

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Apr 2022

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 16, 2022

Completed
1 month until next milestone

Study Start

First participant enrolled

April 1, 2022

Completed
19 days until next milestone

First Posted

Study publicly available on registry

April 20, 2022

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2023

Completed
Last Updated

April 20, 2022

Status Verified

April 1, 2022

Enrollment Period

1.7 years

First QC Date

February 16, 2022

Last Update Submit

April 12, 2022

Conditions

Heart Failure NYHA Class IIHeart Failure NYHA Class IIIHeart Failure NYHA Class IV

Keywords

Heart FailureAngiotensin(1-7)

Outcome Measures

Primary Outcomes (42)

  • Baseline Blood Biomarkers - Neurology 4-Pleax A, pTau-181, and pTau 231 as measured by the Quanterix Simoa Neurology 4-plex A and Simoa pTau-181 and 283 advantage kits

    We will use the Quanterix Simoa Neurology 4-Plex A (N4PA) Advantage kit to measure Neurology 4-Plex A (GFAP, NF-light, Total Tau, UCH-L1 and the Simoa pTau-181 and 283 Advantage kits to measure pTau-181 and pTau 231.

    These measurements will be taken at baseline

  • Baseline evaluations of associative, verbal memory as measured by the verbal paired associates task (version 2)

    The verbal paired associates task (version 2) will be used to evaluate associative, verbal memory. Scores can range from 0 to 36 with higher scores indicating better outcomes.

    These measurements will be taken at baseline

  • Baseline evaluations of associative, visual memory as measured by the Face Name Associative Memory Test

    The Face Name Associative Memory Test will be used to evaluate associative, visual memory. Scores can range from 0 to 12 with higher scores indicating better outcomes.

    These measurements will be taken at baseline

  • Baseline evaluations of pattern separation memory as measured by the Mnemonic Similarity Task

    The Mnemonic Similarity Task will be used to evaluate pattern separation memory. Scores can range from 0 to 1.0 with higher scores indicating better outcomes

    These measurements will be taken at baseline

  • Baseline evaluations of executive functions - updating/working memory as measured by the Keep Track Task

    The Keep Track Task will be used to evaluate executive function - updating/working memory. Scores can range from 0 to 30 with higher scores indicating better performance.

    These measurements will be taken at baseline

  • Baseline evaluations of executive functions - switching as measured by the Number-Letter Task

    The Number-Letter task will be used to evaluate executive function - switching. Scores can range from 0.2sec to 10 sec with higher scores indicating worse outcomes

    These measurements will be taken at baseline

  • Baseline evaluations of executive functions - attention/inhibition as measured by the Flanker Task

    The Flanker Task will be used to evaluate executive function - attention/inhibition. Scores can range from 200ms - 2000ms with higher scores indicating worse outcomes

    These measurements will be taken at baseline

  • Baseline evaluations of processing speeds - simple/complex processing speeds as measured by the Deary-Liewald Reaction Time Task

    The Deary-Liewald Reaction Time Task will evaluate processing speed - simple/complex processing speed. Scores can range from 200ms - 1500ms with higher scores indicating worse outcomes

    These measurements will be taken at baseline

  • Baseline evaluations of reading ability/vocabulary as measured by the North American Reading Test

    The North American Reading Test will be used to evaluate reading ability/vocabulary. Scores can range from 0 to 61 with higher score indicating better outcomes

    These measurements will be taken at baseline

  • Baseline evaluations of global cognitive functioning as measured by the Montreal Cognitive Assessment

    The Montreal Cognitive Assessment will be used to evaluate global cognitive functioning/ Scores can range from 0 - 30 with higher scores indicating better outcomes.

    These measurements will be taken at baseline

  • Participants sleep quality will be assessed as measured by the Pittsburgh Sleep Quality Index

    The Pittsburgh Sleep Quality Index will be used to assess sleep quality. Scores can range from 0 to 21 with higher scores indicating worse outcomes

    These measurements will be taken at baseline

  • Participants quality of life will be assessed as measured by the World Health Organization Quality of Life - BREF (WHOQOL-BREF)

    The World Health Organization Quality of Life - BREF (WHOQOL-BREF) will be used to assess participant's quality of life. Score can range from 3 to 40 with higher scores indicating better outcomes

    These measurements will be taken at baseline

  • Participants disability due to health/mental health conditions will be assessed as measured by the World Health Organization Disability Assessment Schedule 2.0

    The World Health Organization Disability Assessment Schedule 2.0 will be used to assess participant's disability due to health/mental health conditions. Scores can range from 7 to 36 with higher scores indicating worse outcomes.

    These measurements will be taken at baseline

  • Participants physical activity will be assessed as measured by Rapid Assessment of Physical Activity

    The Rapid Assessment of Physical Activity will be used to assess participant's physical activity. Scores can range from 1 to 10 with higher scores indicating better outcomes.

    These measurements will be taken at baseline

  • Participants heart failure health status will be assessed as measured by the Kansas City Cardiomyopathy Questionnaire

    The Kansas City Cardiomyopathy Questionnaire. Scores can range from 12 to 118 with higher scores indicating better outcomes

    These measurements will be taken at baseline

  • Participants independent living skills will be assessed as measured by the Lawton-Brody Instrumental Activities of Daily Living Scale (I.A.D.L)

    The Lawton-Brody Instrumental Activities of Daily Living Scale (I.A.D.L). Scores can range from 0 to 8 with higher scores indicating better outcomes.

    These measurements will be taken at baseline

  • 12-week Blood Biomarkers - Neurology 4-Pleax A, pTau-181, and pTau 231 as measured by the Quanterix Simoa Neurology 4-plex A and Simoa pTau-181 and 283 advantage kits

    We will use the Quanterix Simoa Neurology 4-Plex A (N4PA) Advantage kit to measure Neurology 4-Plex A (GFAP, NF-light, Total Tau, UCH-L1 and the Simoa pTau-181 and 283 Advantage kits to measure pTau-181 and pTau 231.

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of associative, verbal memory as measured by the verbal paired associates task (version 2)

    The verbal paired associates task (version 2) will be used to evaluate associative, verbal memory. Scores can range from 0 to 36 with higher scores indicating better outcomes.

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of associative, visual memory as measured by the Face Name Associative Memory Test

    The Face Name Associative Memory Test will be used to evaluate associative, visual memory. Scores can range from 0 to 12 with higher scores indicating better outcomes.

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of pattern separation memory as measured by the Mnemonic Similarity Task

    The Mnemonic Similarity Task will be used to evaluate pattern separation memory. Scores can range from 0 to 1.0 with higher scores indicating better outcomes

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of executive functions - updating/working memory as measured by the Keep Track Task

    The Keep Track Task will be used to evaluate executive function - updating/working memory. Scores can range from 0 to 30 with higher scores indicating better performance.

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of executive functions - switching as measured by the Number-Letter Task

    The Number-Letter task will be used to evaluate executive function - switching. Scores can range from 0.2sec to 10 sec with higher scores indicating worse outcomes

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of executive functions - attention/inhibition as measured by the Flanker Task

    The Flanker Task will be used to evaluate executive function - attention/inhibition. Scores can range from 200ms - 2000ms with higher scores indicating worse outcomes

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of processing speeds - simple/complex processing speeds as measured by the Deary-Liewald Reaction Time Task

    The Deary-Liewald Reaction Time Task will evaluate processing speed - simple/complex processing speed. Scores can range from 200ms - 1500ms with higher scores indicating worse outcomes

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of reading ability/vocabulary as measured by the North American Reading Test

    The North American Reading Test will be used to evaluate reading ability/vocabulary. Scores can range from 0 to 61 with higher score indicating better outcomes

    These measurements will be taken after the 12 week drug course

  • 12-week evaluations of global cognitive functioning as measured by the Montreal Cognitive Assessment

    The Montreal Cognitive Assessment will be used to evaluate global cognitive functioning/ Scores can range from 0 - 30 with higher scores indicating better outcomes.

    These measurements will be taken after the 12 week drug course

  • 12-month Blood Biomarkers - Neurology 4-Pleax A, pTau-181, and pTau 231 as measured by the Quanterix Simoa Neurology 4-plex A and Simoa pTau-181 and 283 advantage kits

    We will use the Quanterix Simoa Neurology 4-Plex A (N4PA) Advantage kit to measure Neurology 4-Plex A (GFAP, NF-light, Total Tau, UCH-L1 and the Simoa pTau-181 and 283 Advantage kits to measure pTau-181 and pTau 231.

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of associative, verbal memory as measured by the verbal paired associates task (version 2)

    The verbal paired associates task (version 2) will be used to evaluate associative, verbal memory. Scores can range from 0 to 36 with higher scores indicating better outcomes.

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of associative, visual memory as measured by the Face Name Associative Memory Test

    The Face Name Associative Memory Test will be used to evaluate associative, visual memory. Scores can range from 0 to 12 with higher scores indicating better outcomes.

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of pattern separation memory as measured by the Mnemonic Similarity Task

    The Mnemonic Similarity Task will be used to evaluate pattern separation memory. Scores can range from 0 to 1.0 with higher scores indicating better outcomes

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of executive functions - updating/working memory as measured by the Keep Track Task

    The Keep Track Task will be used to evaluate executive function - updating/working memory. Scores can range from 0 to 30 with higher scores indicating better performance.

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of executive functions - switching as measured by the Number-Letter Task

    The Number-Letter task will be used to evaluate executive function - switching. Scores can range from 0.2sec to 10 sec with higher scores indicating worse outcomes

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of executive functions - attention/inhibition as measured by the Flanker Task

    The Flanker Task will be used to evaluate executive function - attention/inhibition. Scores can range from 200ms - 2000ms with higher scores indicating worse outcomes

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of processing speeds - simple/complex processing speeds as measured by the Deary-Liewald Reaction Time Task

    The Deary-Liewald Reaction Time Task will evaluate processing speed - simple/complex processing speed. Scores can range from 200ms - 1500ms with higher scores indicating worse outcomes

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of reading ability/vocabulary as measured by the North American Reading Test

    The North American Reading Test will be used to evaluate reading ability/vocabulary. Scores can range from 0 to 61 with higher score indicating better outcomes

    These measurements will be taken at the 12 month follow up

  • 12-month evaluations of global cognitive functioning as measured by the Montreal Cognitive Assessment

    The Montreal Cognitive Assessment will be used to evaluate global cognitive functioning/ Scores can range from 0 - 30 with higher scores indicating better outcomes.

    These measurements will be taken at the 12 month follow up

  • Participants sleep quality will be assessed as measured by the Pittsburgh Sleep Quality Index

    The Pittsburgh Sleep Quality Index will be used to assess sleep quality. Scores can range from 0 to 21 with higher scores indicating worse outcomes

    These measurements will be taken at the 12 month follow up

  • Participants disability due to health/mental health conditions will be assessed as measured by the World Health Organization Disability Assessment Schedule 2.0

    The World Health Organization Disability Assessment Schedule 2.0 will be used to assess participant's disability due to health/mental health conditions. Scores can range from 7 to 36 with higher scores indicating worse outcomes.

    These measurements will be taken at the 12 month follow up

  • Participants quality of life will be assessed as measured by the World Health Organization Quality of Life - BREF (WHOQOL-BREF)

    The World Health Organization Quality of Life - BREF (WHOQOL-BREF) will be used to assess participant's quality of life. Score can range from 3 to 40 with higher scores indicating better outcomes

    These measurements will be taken at the 12 month follow up

  • Participants physical activity will be assessed as measured by Rapid Assessment of Physical Activity

    The Rapid Assessment of Physical Activity will be used to assess participant's physical activity. Scores can range from 1 to 10 with higher scores indicating better outcomes.

    These measurements will be taken at the 12 month follow up

  • Participants heart failure health status will be assessed as measured by the Kansas City Cardiomyopathy Questionnaire

    The Kansas City Cardiomyopathy Questionnaire. Scores can range from 12 to 118 with higher scores indicating better outcomes

    These measurements will be taken at the 12 month follow up

  • Participants independent living skills will be assessed as measured by the Lawton-Brody Instrumental Activities of Daily Living Scale (I.A.D.L)

    The Lawton-Brody Instrumental Activities of Daily Living Scale (I.A.D.L). Scores can range from 0 to 8 with higher scores indicating better outcomes.

    These measurements will be taken at the 12 month follow up

Study Arms (2)

Ang-(1-7)

EXPERIMENTAL

30 participants will take 100 micrograms of Ang-(1-7) a day via subcutaneous injection for 90 days

Drug: Angiotensin 1-7

Saline Placebo

PLACEBO COMPARATOR

10 participants will take 100 micrograms of saline placebo a day via subcutaneous injection for 90 days

Drug: Saline solution

Interventions

Angiotensin 1-7DRUG

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.

Ang-(1-7)
Saline solutionDRUG

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.

Saline Placebo

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants may be included in the study if they are:
  • years old and older
  • Diagnosed at least 90 days prior to enrollment with stable NYHA Class II-IV HF, with symptoms during mild or moderate exercise but not at rest (i.e., shortness of breath),
  • On a stable medical regimen and free from hospitalizations in the prior 30 days,
  • Fluent English speakers.

You may not qualify if:

  • Participants will be excluded from the study if there is evidence of:
  • Decompensated heart failure
  • Symptoms or signs of active coronary ischemia
  • Systolic blood pressure \<95 mmHg
  • Significant lung disease (FEV1\< 1.5 L, pO2 \<70 on room air, pCO2 \>45)
  • Active substance abuse or a history of substance abuse with cocaine, ecstasy, LSD, or IV drugs
  • History of or current seizure disorder or on medications for seizures (with the exception of childhood febrile seizures)
  • Neurological, psychiatric, or medical illness or injury expected to interfere with cognitive function including but not limited to stroke, head injury, Alzheimer's, Parkinson's, or brain cancer
  • Current depression (Patient Health Questionnaire-9 score \>10)
  • Any condition which may prevent the subject from adhering to the study protocol such as significantly impaired vision.\\
  • Note: Participants that have contraindications for MRI may be enrolled, but will not take part in the MRI portion of the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Banner - University Medical Center

Phoenix, Arizona, 85006, United States

Location

University of Arizona

Tucson, Arizona, 85721, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

angiotensin I (1-7)Saline Solution

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Lee Ryan, Ph.D.

    University of Arizona

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristina Irwin

CONTACT

(520)626-4571kbirwin@arizona.edu

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Masking Details
Participants will not know which treatment they're receiving. Research staff and patients care providers will have access to which treatment patients are receiving.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Following baseline assessments of cognitive function, MRI and plasma Nfl levels, 40 subjects who have consented to participate in the Ang-(1-7) sub-study and will be randomly assigned to be given either Ang-(1-7) (100 micrograms/kg/day via subcutaneous injection) for 90 days (n=30) or saline placebo (n=10).
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Department Head

Study Record Dates

First Submitted

February 16, 2022

First Posted

April 20, 2022

Study Start

April 1, 2022

Primary Completion

December 1, 2023

Study Completion

December 1, 2023

Last Updated

April 20, 2022

Record last verified: 2022-04

Data Sharing

IPD Sharing
Will not share

Locations

US(2)