Clinical trial NCT06645769: Na-Phenylbutyrate VAscular Trial
Official title: Na-Phenylbutyrate VAscular Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Diabetes
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2024-10-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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.

Primary outcomes:
measure: Systemic vascular resistance
timeFrame: from enrollment to the end of participation at 8 weeks
Secondary outcomes:
measure: Plasma BCAAs
timeFrame: from enrollment to the end of participation at 8 weeks
measure: Flow-mediated dilation (FMD)
timeFrame: from enrollment to the end of participation at 8 weeks
measure: Carotid femoral pulse wave velocity (PWV)
timeFrame: from enrollment to the end of participation at 8 weeks
Other outcomes:
measure: Home ambulatory mean pressure and pulse pressure
timeFrame: from enrollment to the end of participation at 8 weeks
measure: Cardiac Ejection Fraction
timeFrame: from enrollment to the end of participation at 8 weeks
Locations:
Study officials:
affiliation: University of Pennsylvania
name: Zoltan Arany, MDPHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.