Novel Approaches for Improving Vascular Function in Veterans With HFpEF

NCT06312748 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CARB-019-20S138675
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This project will evaluate the impact of L-Citrulline, tetrahydrobiopterin (BH4), and atorvastatin administration on physical capacity and vascular function in Veterans with heart failure with preserved ejection fraction (HFpEF).

Conditions

Heart Failure With Preserved Ejection Fraction; Inflammation

Keywords

vascular health; exercise tolerance; HFpEF; nitric oxide

Outcome Measures

Primary Outcomes (1)

• Flow-mediated dilation (FMD)

  Peak change in brachial artery diameter (%)

  Baseline, Day 90

Secondary Outcomes (1)

• Passive Limb Movement (PLM)

  Baseline, Day 90

Study Arms (6)

L-Citrulline, Then Placebo

EXPERIMENTAL

Participants will receive a 90-day supply of L-Citrulline and perform baseline assessments of resting arterial blood pressure, ECT, arterial elasticity/pulse contour analysis, flow-mediated vasodilation and passive limb movement procedures. Participants will return to the laboratory for up to 5 additional study visits (days 10, 20, 30, 60, and 90) and repeat the experimental protocol. After a two-week washout period, participants will receive a 90-day supply of Placebo and perform baseline and follow-up assessments as above.

Drug: L-Citrulline; Drug: Placebo for L-Citrulline

BH4, Then Placebo

EXPERIMENTAL

Participants will receive a 90-day supply of BH4 and perform baseline assessments of resting arterial blood pressure, ECT, arterial elasticity/pulse contour analysis, flow-mediated vasodilation and passive limb movement procedures. Participants will return to the laboratory for up to 5 additional study visits (days 10, 20, 30, 60, and 90) and repeat the experimental protocol. After a two-week washout period, participants will receive a 90-day supply of Placebo and perform baseline and follow-up assessments as above.

Drug: BH4; Drug: Placebo for BH4

Atorvastatin, Then Placebo

EXPERIMENTAL

Participants will receive a 90-day supply of Atorvastatin and perform baseline assessments of resting arterial blood pressure, ECT, arterial elasticity/pulse contour analysis, flow-mediated vasodilation and passive limb movement procedures. Participants will return to the laboratory for up to 5 additional study visits (days 10, 20, 30, 60, and 90) and repeat the experimental protocol. After a two-week washout period, participants will receive a 90-day supply of Placebo and perform baseline and follow-up assessments as above.

Drug: Atorvastatin; Drug: Placebo for Atorvastatin

Placebo, Then L-Citrulline

EXPERIMENTAL

Participants will receive a 90-day supply of Placebo and perform baseline assessments of resting arterial blood pressure, ECT, arterial elasticity/pulse contour analysis, flow-mediated vasodilation and passive limb movement procedures. Participants will return to the laboratory for up to 5 additional study visits (days 10, 20, 30, 60, and 90) and repeat the experimental protocol. After a two-week washout period, participants will receive a 90-day supply of L-Citrulline and perform baseline and follow-up assessments as above.

Drug: L-Citrulline; Drug: Placebo for L-Citrulline

Placebo, Then BH4

EXPERIMENTAL

Participants will receive a 90-day supply of Placebo and perform baseline assessments of resting arterial blood pressure, ECT, arterial elasticity/pulse contour analysis, flow-mediated vasodilation and passive limb movement procedures. Participants will return to the laboratory for up to 5 additional study visits (days 10, 20, 30, 60, and 90) and repeat the experimental protocol. After a two-week washout period, participants will receive a 90-day supply of BH4 and perform baseline and follow-up assessments as above.

Drug: BH4; Drug: Placebo for BH4

Placebo, Then Atorvastatin

EXPERIMENTAL

Participants will receive a 90-day supply of Placebo and perform baseline assessments of resting arterial blood pressure, ECT, arterial elasticity/pulse contour analysis, flow-mediated vasodilation and passive limb movement procedures. Participants will return to the laboratory for up to 5 additional study visits (days 10, 20, 30, 60, and 90) and repeat the experimental protocol. After a two-week washout period, participants will receive a 90-day supply of Atorvastatin and perform baseline and follow-up assessments as above.

Drug: Atorvastatin; Drug: Placebo for Atorvastatin

Interventions

L-Citrulline DRUG

100 mg tablet

L-Citrulline, Then Placebo; Placebo, Then L-Citrulline

BH4 DRUG

10mg/kg

Also known as: Kuvan®, sapropterin dihydrochloride

BH4, Then Placebo; Placebo, Then BH4

Placebo for L-Citrulline DRUG

L-Citrulline-matched Placebo tablet

L-Citrulline, Then Placebo; Placebo, Then L-Citrulline

Placebo for BH4 DRUG

BH4-matched Placebo

BH4, Then Placebo; Placebo, Then BH4

Atorvastatin DRUG

10 mg tablet

Also known as: Lipitor®

Atorvastatin, Then Placebo; Placebo, Then Atorvastatin

Placebo for Atorvastatin DRUG

Atorvastatin-matched Placebo

Atorvastatin, Then Placebo; Placebo, Then Atorvastatin

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older and able to give written informed consent.
• New York Heart Association (NYHA) functional class I, II, or III.
• Left Ventricular Ejection Fraction (LVEF) \> 50%.
• Plasma Brain Natriuretic Peptide (BNP) equal to or greater than 150 pg/mL or NT-proBNP equal to or greater than 600 pg/mL at Visit 1, or a BNP equal to or great than 100 pg/mL (or NT-proBNP equal to or greater than 400 pg/mL) and a hospitalization for heart failure within the last 12 months.

You may not qualify if:

• History of hypersensitivity or allergy to any lipophilic statin.
• Prior EF \<50%.
• NYHA Class IV.
• Patients with HFpEF secondary to significant uncorrected primary valvular disease.
• Active liver disease or unexplained persistent elevations in serum transaminase.
• Women who are pregnant or may become pregnant.
• Patients currently treated with antioxidants, nitrates, PDE-5 inhibitors, or statins.

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Utah: collaborator

Study Sites (1)

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148-0001, United States

RECRUITING

MeSH Terms

Conditions

Inflammation

Interventions

Citrulline; sapropterin; Atorvastatin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• David W. Wray, PhD

  VA Salt Lake City Health Care System, Salt Lake City, UT

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David W Wray, PhD

CONTACT

(801) 582-1565; David.Wray2@va.gov

Misti R Seppi, MBA BS AAS

CONTACT

(801) 582-1565; Misti.Seppi@va.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: A block randomization method will be used to randomize participants into equal groups and will be handled by investigational pharmacist.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: March 15, 2024
• Study Start: May 19, 2021
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2030
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)