Clinical trial NCT02684786: A Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension
Official title: A Phase I Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Pulmonary Artery Hypertension
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2016-02-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pulmonary hypertension Group 2 (PH 2) associated with left-sided heart disease is relatively common, is associated with a poor prognosis, and unfortunately there are no proven medical treatments beyond attempts at correcting the left sided heart disease. Many PH 2 patients have evidence of active constriction of blood vessels from increased nerve traffic. Use of agents or procedures which produce a reversible chemical blockage of this nerve traffic have not been systematically tested in PH 2. The investigators will test whether acute interruption of sympathetic nervous system tone, which local anesthetic block of the stellate ganglion in the neck, will improve PH2, and also test whether the high blood pressure drug reserpine, which blocks sympathetic nerve activity, will do so during a one month trial period.

Detailed description: Background. Pulmonary hypertension Group 2 (PH 2) associated with left-sided heart disease is relatively common, is associated with a poor prognosis, and unfortunately there are no proven medical treatments beyond attempts at correcting the left sided heart disease. Many PH 2 patients have evidence of vasoconstriction and increased sympathetic nervous system activity. Use of agents or procedures which produce a reversible chemical sympathectomy have not been systematically tested in PH 2.

Methods. Two groups will be eligible for participation: Group 1 (n=10): Patients with PH 2 previously documented by echocardiography (echo), 6 minute walk test, biomarkers, and right heart catheterization (RHC) will receive reserpine, 0.05 mg per day for two weeks, then, 0.1 mg per day for an additional two weeks. After one month, patients will be reassessed for New York Heart Association (NYHA) class and drug side effects, echocardiography, 6 minute walk assessment, and brain natriuretic peptide (BNP). Group 2 patients (n=10) will have clinically suspected PH 2 and be scheduled to undergo clinically indicated RHC. If during RHC PH 2 is confirmed, after assessment of nitric oxide responsiveness, their baseline hemodynamics will be re-established over 10 minutes, and a left stellate ganglion block with lidocaine will be performed, and immediate hemodynamic responsiveness assessed. Four hours post-procedure, a side effect questionnaire will be obtained. Group 2 patients who complete RHC will then begin reserpine treatment in the same manner as Group I patients.

Hypothesis and Impact. PH 2 is the most common type of pulmonary hypertension. The current diagnostic and therapeutic strategy aims to treat the left sided heart disease in attempt to normalize pulmonary artery pressure. The place of selective pulmonary vasodilators is undefined. The investigator's approach addresses inhibition of adverse pulmonary vasoconstriction mediated by the sympathetic nervous system in PH 2.

Eligibility criteria: Inclusion criteria:

* Prior right heart catheterization, with mean pulmonary artery pressure \> 25 mm Hg, pulmonary capillary wedge pressure \> 15 mm Hg, and diastolic pressure gradient (pulmonary artery diastolic pressure - mean pulmonary capillary wedge pressure) ≥ 7 mm Hg OR clinically suspected group 2 pulmonary hypertension from non-invasive testing with planned right heart catheterization (RHC).
* On stable diuretic therapy
* Able to attend end-study visit 4 weeks after study entry

Exclusion criteria:

* Anticipated surgery to correct heart lesion responsible for pulmonary hypertension
* Need for heparinization for right heart catheterization (not standard practice, but sometimes utilized)
* History of depression, or treatment with tricyclic anti-depressant, serotonin uptake inhibitor, monamine oxidase inhibitor
* Severe renal or hepatic impairment, creatinine clearance \< 30 ml/minute or renal replacement therapy or post-kidney transplant, abnormal liver function with elevated enzymes\> 1.5 times the upper limit of normal or prior liver transplant.
* Systolic blood pressure \<100 mm Hg
* Heart rate \< 60 beats per minute
* Inability to independently complete telephone follow-up at two weeks, and clinic end-study visit at 4 weeks.
* Pulmonary edema
* Infiltrative cardiomyopathy - amyloidosis
* Symptomatic orthostatic hypotension
* Women of childbearing age who have not had surgical sterilization and are not using oral contraceptives, or who's spouse has not had surgical sterilization will be excluded due to the length of the trial and the possibility that they could become pregnant after entry.
* Uncontrolled heartburn
* Prior surgery to the left neck, for example, carotid endarterectomy, or other surgery which would increase the risk of stellate ganglion block
* Known sensitivity, allergy, or contraindication to lidocaine, any local anesthetic, or reserpine

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: one month
Secondary outcomes:
measure: Number of participants with successful stellate ganglion block
timeFrame: One hour
measure: Effect of stellate ganglion block on heart rate
timeFrame: One hour
measure: Change in 6 minute walk distance from one month of reserpine therapy
timeFrame: One month
measure: Change in brain natriuretic peptide (BNP) from one month of reserpine therapy
timeFrame: One month
measure: Change in Doppler derived mean pulmonary artery pressure from one month of reserpine therapy
timeFrame: One month
measure: Change in blood pressure from one month of reserpine therapy
timeFrame: One month
measure: Change in Minnesota Living with heart failure questionnaire from one month of reserpine therapy
timeFrame: One month
measure: Hemodynamic effect of stellate ganglion block
timeFrame: One hour
measure: Hemodynamic effect of stellate ganglion block
timeFrame: One hour
measure: Hemodynamic effect of stellate ganglion block
timeFrame: One hour
measure: Hemodynamic effect of stellate ganglion block
timeFrame: One hour
measure: Hemodynamic effect of stellate ganglion block
timeFrame: One hour
measure: Change in heart rate from one month of reserpine therapy
timeFrame: One month
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Joseph Blackshear, MD
role: PRINCIPAL_INVESTIGATOR
References: