Pulmonary Artery HypertensionPhase 1NCT02684786
A Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension
A Phase 1 study testing reserpine, stellate ganglion block and lidocaine in people with Pulmonary Artery Hypertension, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Pulmonary Artery Hypertension
- What is being tested?
- reserpine, stellate ganglion block and lidocaine
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension
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.
Read the 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.
- Conditions
- Pulmonary Artery Hypertension
- Being tested
- reserpine, stellate ganglion block, lidocaine
- Medical subject headings
- Familial Primary Pulmonary Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
reserpineDrug
Patients with qualifying hemodynamics from prior right heart catheterization will receive open label reserpine, 0.05 mg by mouth daily for two weeks, then 0.10 mg by mouth daily for two weeks, and then have repeat non-invasive assessments of status
stellate ganglion blockProcedure or surgery
Patients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward
lidocaineDrug
Patients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward
| Study group | Role | What they receive |
|---|---|---|
| Prior right heart catheterization | Experimental | Patients with qualifying hemodynamics from prior right heart catheterization will receive open label reserpine, 0.05 mg by mouth daily for two weeks, then 0.10 mg by mouth daily for two weeks, and then have repeat non-invasive assessments of status. Receives: Drug: reserpine |
| Scheduled for right heart catheterization | Experimental | Patients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward Receives: Procedure: stellate ganglion block; Drug: lidocaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Adverse events of interest are for stellate ganglion block: pulmonary edema, bradycardia requiring treatment, hypotension requiring treatment, arrhythmia, pneumothorax, hoarseness, dysphagia, globus, left upper extremity weakness. For reserpine, heart failure hospitalization, syncope, all cause hospitalization, bradycardia requiring treatment, hypotension requiring treatment, new arrhythmia, edema requiring an increase in diuretics, depression, lethargy, nasal stuffiness, dizziness, orthostatic hypotension, falls, nightmares, sexual dysfunction, anxiety, dyspepsia.
Adverse events classed as serious:
- Life threatening serious adverse events including acute coronary syndrome with active ischemia, fatal arrhythmias, myocardial infarction, acute kidney injury, cardiogenic shock, stroke, pulmonary embolization, arterial and/or venous thrombosis, systemic embolization, severe hypotension, respiratory failure and death
- Prolonged hospitalization or rehospitalization
Measured: one month
Secondary outcomes (13)
Number of participants with successful stellate ganglion block
Stellate block: frequency of the occurrence of ptosis and conjunctival flushing.
Measured: One hour
Effect of stellate ganglion block on heart rate
Heart rate before and after stellate ganglion block
Measured: One hour
Change in 6 minute walk distance from one month of reserpine therapy
Six minute walk distance, meters, baseline compared to one month
Measured: One month
Change in brain natriuretic peptide (BNP) from one month of reserpine therapy
BNP, pg/ml, baseline compared to one month
Measured: One month
Change in Doppler derived mean pulmonary artery pressure from one month of reserpine therapy
Mean pulmonary artery pressure estimate, mm Hg
Measured: One month
Change in blood pressure from one month of reserpine therapy
Blood pressure, mm Hg, baseline versus one month
Measured: One month
Change in Minnesota Living with heart failure questionnaire from one month of reserpine therapy
Minnesota Living with heart failure questionnaire aggregate score, baseline versus one month
Measured: One month
Hemodynamic effect of stellate ganglion block
Blood pressure, mm Hg, before and after stellate ganglion block
Measured: One hour
Hemodynamic effect of stellate ganglion block
Pulmonary artery pressure, mm Hg, before and after stellate ganglion block
Measured: One hour
Hemodynamic effect of stellate ganglion block
Pulmonary capillary wedge pressure, mm Hg, before and after stellate ganglion block
Measured: One hour
Hemodynamic effect of stellate ganglion block
right atrial pressure, mm Hg, before and after stellate ganglion block
Measured: One hour
Hemodynamic effect of stellate ganglion block
Cardiac output, liters per minute, before and after stellate ganglion block
Measured: One hour
Change in heart rate from one month of reserpine therapy
Heart rate, baseline versus one month
Measured: One month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2016 (estimated)
- Study startJul 2016
- Primary completionJul 2016
- Study completionJul 2016
Why it stopped: IRB did not approve
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Artery HypertensionStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph L. Blackshear, Mayo Clinic
- Investigators
- Joseph Blackshear, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02684786
- Sponsor's protocol ID
- 16-000928
- Status last verified
- May 2019
- First submitted
- 4 Feb 2016
- Last updated
- 22 May 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT02684786
- Acronym / sponsor ID
- 16-000928
- Conditions
- Pulmonary Artery Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: IRB did not approve
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 18 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prior right heart catheterization | Experimental | Drug: reserpinePatients with qualifying hemodynamics from prior right heart catheterization will receive open label reserpine, 0.05 mg by mouth daily for two weeks, then 0.10 mg by mouth daily for two weeks, and then have repeat non-invasive assessments of status. |
| Scheduled for right heart catheterization | Experimental | Procedure: stellate ganglion block, Drug: lidocainePatients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| reserpinePatients with qualifying hemodynamics from prior right heart catheterization will receive open label reserpine, 0.05 mg by mouth daily for two weeks, then 0.10 mg by mouth daily for two weeks, and then have repeat non-invasive assessments of status | Drug | Prior right heart catheterization |
| stellate ganglion blockPatients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward | Procedure or surgery | Scheduled for right heart catheterization |
| lidocainePatients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward | Drug | Scheduled for right heart catheterization |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: one month
Adverse events of interest are for stellate ganglion block: pulmonary edema, bradycardia requiring treatment, hypotension requiring treatment, arrhythmia, pneumothorax, hoarseness, dysphagia, globus, left upper extremity weakness. For reserpine, heart failure hospitalization, syncope, all cause hospitalization, bradycardia requiring treatment, hypotension requiring treatment, new arrhythmia, edema requiring an increase in diuretics, depression, lethargy, nasal stuffiness, dizziness, orthostatic hypotension, falls, nightmares, sexual dysfunction, anxiety, dyspepsia. Adverse events classed as serious: * Life threatening serious adverse events including acute coronary syndrome with active ischemia, fatal arrhythmias, myocardial infarction, acute kidney injury, cardiogenic shock, stroke, pulmonary embolization, arterial and/or venous thrombosis, systemic embolization, severe hypotension, respiratory failure and death * Prolonged hospitalization or rehospitalization
13 secondary outcomes
Number of participants with successful stellate ganglion block
Time frame: One hour
Effect of stellate ganglion block on heart rate
Time frame: One hour
Change in 6 minute walk distance from one month of reserpine therapy
Time frame: One month
Change in brain natriuretic peptide (BNP) from one month of reserpine therapy
Time frame: One month
Change in Doppler derived mean pulmonary artery pressure from one month of reserpine therapy
Time frame: One month
Change in blood pressure from one month of reserpine therapy
Time frame: One month
Change in Minnesota Living with heart failure questionnaire from one month of reserpine therapy
Time frame: One month
Hemodynamic effect of stellate ganglion block
Time frame: One hour
Hemodynamic effect of stellate ganglion block
Time frame: One hour
Hemodynamic effect of stellate ganglion block
Time frame: One hour
Hemodynamic effect of stellate ganglion block
Time frame: One hour
Hemodynamic effect of stellate ganglion block
Time frame: One hour
Change in heart rate from one month of reserpine therapy
Time frame: One month
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2019.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Blackshear, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing reserpine, stellate ganglion block and lidocaine in people with Pulmonary Artery Hypertension, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2019.