Na-Phenylbutyrate VAscular Trial (NAPVAT)

This study will investigate if the drug sodium phenylbutyrate (NaPB) impacts blood pressure and vascular function in healthy volunteers and in patients with diabetes.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes
• Intervention / Treatment: Drug: Sodium Phenylbutyrate; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Claire Brady; Phone Number: 8573344274; Email: Claire.Brady@Pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Over 18 years of age and less than 60.
• Healthy subjects will have no history of diabetes or prediabetes.
• Diabetes subjects can be either insulin dependent or not.
• Able to provide written consent and to comply with the procedures of the study protocol.

Exclusion Criteria:

• Age <18 or >60
• Pregnant or lactating women.
• Subjects with hypertension or taking any vasodilatory medications, any steroidal drugs, haloperidol, or valproic acid.
• Patients with congestive heart failure, severe renal insufficiency, hepatic failure, or known sodium retention with oedema.
• Active alcohol or substance abuse.
• Use of tobacco within the previous six months.
• Unble to provide written consent and to comply with the procedures of the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo control	Other: Placebo; will be compared to NaPB
Experimental: NaPB administration	Drug: Sodium Phenylbutyrate; will be compared to placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic vascular resistance	Arterial hemodynamics and echocardiography to assess systemic vascular resistance, in dynes × sec/cm5.	from enrollment to the end of participation at 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma BCAAs	Plasma branched chain amino acid levels, measured by mass spectrometry (in microMolar)	from enrollment to the end of participation at 8 weeks
Flow-mediated dilation (FMD)	FMD is a non-invasive test that measures the endothelial function of blood vessels. FMD is measured as a percentage increase in the diameter of an artery during hyperemia (%).	from enrollment to the end of participation at 8 weeks
Carotid femoral pulse wave velocity (PWV)	Pulse wave velocity (PWV) is the distance a pulse wave travels in a specific arterial segment divided by the time it takes to travel that distance (units: m/sec). PWV is a marker of cardiovascular risk.	from enrollment to the end of participation at 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Home ambulatory mean pressure and pulse pressure	At home blood pressure cuff used to determine changes in blood pressure with normal activities (mmHg)	from enrollment to the end of participation at 8 weeks
Cardiac Ejection Fraction	echocardiography will be used to determine ejection fraction (%)	from enrollment to the end of participation at 8 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Zoltan Arany, MDPHD, University of Pennsylvania

Publications and helpful links

General Publications

• Murashige D, Jung JW, Neinast MD, Levin MG, Chu Q, Lambert JP, Garbincius JF, Kim B, Hoshino A, Marti-Pamies I, McDaid KS, Shewale SV, Flam E, Yang S, Roberts E, Li L, Morley MP, Bedi KC Jr, Hyman MC, Frankel DS, Margulies KB, Assoian RK, Elrod JW, Jang C, Rabinowitz JD, Arany Z. Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure. Cell Metab. 2022 Nov 1;34(11):1749-1764.e7. doi: 10.1016/j.cmet.2022.09.008. Epub 2022 Oct 11.
• Vanweert F, Neinast M, Tapia EE, van de Weijer T, Hoeks J, Schrauwen-Hinderling VB, Blair MC, Bornstein MR, Hesselink MKC, Schrauwen P, Arany Z, Phielix E. A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes. Nat Commun. 2022 Jun 18;13(1):3508. doi: 10.1038/s41467-022-31249-9.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: October 4, 2024
• First Submitted That Met QC Criteria: October 14, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus; Antineoplastic Agents; 4-phenylbutyric acid
• Other Study ID Numbers: NAPVAT; R01HL152446 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No