Conditions: Refractory Hypertension
Keywords: hypertension sympathetic tone resperpine
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 7
Healthy volunteers: no

Brief summary:
The study is deigned to determine if refractory hypertension is attributable to heightened sympathetic tone by quantifying the antihypertensive benefit of reserpine, a sympatholytic agent, in patients failing other classes of antihypertensive agents.

Detailed description:
Patients with refractory hypertension, defined as uncontrolled office blood pressure despite use of 5 or more antihypertensive agents, including a thiazide diuretic and spironolactone. After withdrawal from other centrally-acting agents if needed, enrolled patients will be randomized to open-label reserpine 0.1 mg daily for 4 weeks. Twenty-four hour ambulatory blood pressure monitoring will be done at baseline, after the initial 4-week treatment period. All other antihypertensive medications will remain unchanged during the 4-week treatment period. The primary endpoint will be change in 24-hr ambulatory systolic blood pressure.

Arms:
arm 1: Subjects will receive open-label reserpine 0.1 mg daily for 4 weeks.

Interventions: intervention 1: Reserpine
Intervention descriptions: intervention 1: Open label reserpine 0.1 mg pill orally

Protocol document:
Prot_SAP_000.pdf: 
Date:  11/02/21 
 
Title:  Mechanisms of Refractory Hypertension (Reserpine) 
 
NCT Number:  NCT03223272 
 
Date of Last Protocol Approval:  06/09/21 
 
PI: 
David A. Calhoun, MD 
University of Alabama at Birmingham 
Birmingham, AL 35294 
 
 
 
 


 
Study Protocol 
1.  Study Title:  Mechanisms of Refractory Hypertension (Reserpine) 
2.  Hypothesis:  Reserpine, a potent sympatholytic agent will substantially reduce blood 
pressure (BP) in patients with refractory hypertension. 
3.  Inclusion Criteria:  Patients (age 19-80 years) referred to UAB Hypertension Clinic with 
refractory hypertension defined as uncontrolled office BP adherent with 5 or more 
antihypertensive agents, including a long-acting thiazide diuretic and spironolactone. 
4.  Exclusion Criteria:  chronic kidney disease (eGFR <30 ml/min/1.73 mm), pregnancy 
4.  Primary Endpoint:  Change in 24-hr ambulatory systolic BP 
5.  Study design:  Subjects will be withdrawn from centrally-acting alpha-1 agonists agents (i.e., 
clonidine, guanfacine) over a 1-2-week period, if appropriate.  A baseline 24-hr ambulatory BP 
monitoring will be done with subjects taking all of their normally prescribed antihypertensive 
agents.  Subjects will then be dispensed reserpine 0.1 mg in open-label fashion to be taken daily 
for 4-weeks.  At the end of the 4-week treatment period the 24-hr ambulatory monitoring will 
be repeated. 
6.  Statistical Plan: The protocol will be done as a proof-of-concept.  Values will be presented as 
mean+/-standard deviation.  Change in 24-hr ambulatory systolic BP from baseline to end-of-
treatment will be compared by paired T-test. 
7.  Publication Plan:  Study results will be presented at national hypertension meetings and 
submitted to a peer-reviewed medical journal for consideration of publication.