Neurostimulation of Spinal Nerves That Affect the Heart (Neurostim)

• ClinicalTrials.gov Identifier: NCT01124136
• Recruitment Status: Unknown
• First Posted: May 14, 2010
• Last Update Posted: January 12, 2018
• Sponsor: Jerry Estep, MD
• Collaborator: The Methodist Hospital Research Institute
• Information provided by (Responsible Party): Jerry Estep, MD, The Methodist Hospital Research Institute

Study Description

Brief Summary:

The purpose of this study is to study the use of neurostimulation in chronic advanced refractory heart failure.

The study is determine if it is safe to use neurostimulation in patients with chronic advanced refractory heart failure and to also determine initial observations with regards to its potential effect on heart function and quality of life. The investigators hypothesis is that this study will show both safe and positive effect of neurostimulation on heart failure patients.

Condition or disease	Intervention/treatment	Phase
Chronic Heart Failure	Device: Neurostimulation + Medication Management (Standard of Care); Drug: Standard of Care (Control)	Not Applicable

Detailed Description:

Protocol Summary

Title EVALUATION OF THE SAFETY OF NEUROSTIMULATION IN PATIENTS WITH SYMPTOMATIC HEART FAILURE FEASIBILTIY STUDY

Description A feasibility trial of the use of neurostimulation in chronic advanced refractory heart failure.

Objective To determine the safety of neurostimulation in patients with chronic advanced refractory heart failure and to generate initial observations with regards to its potential effect on ventricular function and quality of life.

Design The trial will be a randomized double blind crossover feasibility trial with 2 week and 1,2,3,4,5,6,7 month clinical follow-up.

After device implantation, patients enrolled in the trial will have been randomly assigned to have device programmed to deliver impulses, active, or to have the device programmed not to deliver impulses, inactive, for 3 months.

After the 3 month initial phase, the devices will be inactivated and a 4 week washout period will convene.

At the end of washout period, patients that were inactive during initial phase will crossover to active and similarly patients that were active during initial phase will crossover to inactive.

Patient Population Patients with non-ischemic or ischemic cardiomyopathy with a length of illness of at least 6 months who have met the inclusion and exclusion criteria.

Enrollment Enrollment of a total of 10 intent-to-treat patients Investigational Sites Up to 2 investigational sites in the US Data Collection Data collection will be obtained in three categories: markers of cardiovascular safety, markers of device-device interactions and markers of efficacy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Heart failure treatment standard of care (SOC) consists of medication management to support heart and manage symptoms. In this study, patients will receive the neurostimulator + SOC or SOC only.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Effect of Neurostimulation in Patients With Symptomatic Heart Failure
• Study Start Date: May 2010
• Estimated Primary Completion Date: October 2018
• Estimated Study Completion Date: November 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Neurostimulation + Medication management; Investigational nerve stimulator device implanted to heart plus standard medication therapy.	Device: Neurostimulation + Medication Management (Standard of Care); In addition to medication management, adding investigational implanted neurostimulator to heart; Other Name: Neurostimulator and medication management; Drug: Standard of Care (Control); Standard of Care Therapy consists of medication management only to support heart for rhythm, anticoagulation, and rate, and comorbid symptoms, i.e. diuretics, lipid lowering.; Other Name: Standard Care, Medical Management only
Standard of Care (Control); Standard of Care treatment is medication management only. Heart failure medications control symptoms and comorbidities, i.e. blood thinners, lipid lowering, and diuretics, and manage heart function, i.e. heart rhythm, rate, and pumping strength.	Drug: Standard of Care (Control); Standard of Care Therapy consists of medication management only to support heart for rhythm, anticoagulation, and rate, and comorbid symptoms, i.e. diuretics, lipid lowering.; Other Name: Standard Care, Medical Management only

Outcome Measures

Primary Outcome Measures :

1. Markers of cardiovascular safety [ Time Frame: 2 years ]
   Markers of cardiovascular safety will include specific clinical events that define worsening of heart failure including hospitalization for worsening heart failure, symptomatic brady-arrhythmia or tachy-arrhythmia necessitating cardioversion or death.
2. Markers of device-device interaction [ Time Frame: 2 years ]
   Markers of device-device interaction will include failure to properly provide pacing or adequate defibrillation or inappropriate shocks. Also, failure to initiate neurostimluation as programmed by the protocol
3. Markers of efficacy [ Time Frame: Average: till the end of the study ]
   Markers of efficacy will include change in left ventricular ejection fraction as determined by echocardiography, change in maximal oxygen consumption as measured by cardio-pulmonary exercise testing, and change in quality of life as measured by the MLHFQ. Other exploratory markers include measurements in diastolic function by echocardiography, changes in neurohormonal and inflammatory markers, specifically BNP, plasma cytokines(TNF alpha and IL 6), complement, and C-reactive protein.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion

1. Male or female ≥18 years;
2. Chronic heart failure NYHA class III-IV of ischemic and non-ischemic etiology;
3. Screening Left ventricular Ejection Fraction (LVEF) ≤ 30% measured at baseline by echocardiography;
4. Screening 6 minute walk test score of less than 450 meters measured at baseline;
5. Hospitalization for heart failure or outpatient IV administration of inotropic agents, human B-natriuretic peptide or IV diuretics within the past 12 months (stable for at least 2 weeks);
6. On standard optimal medical therapy for CHF before medical therapy.*
7. No changes in active cardiac medications during the 1 week prior to treatment;

8. Written informed consent.

   • Patients with current or prior symptoms of heart failure and reduced LVEF should be on stable optimally uptitrated medical therapy recommended according to current guidelines (Circulation. 2005; 112 (12): e154) as standard of care for heart failure therapy in the United States. This minimally includes an ACE-inhibitor (ACE-I) at stable doses for 1 month prior to enrollment, if tolerated, and a beta blocker (carvedilol, metoprolol succinate, or bisoprolol) for 3 months prior to enrollment, if tolerated, with a stable up-titrated dose for 1 month prior to enrollment. This also includes an Angiotensin II Receptor Blocker (ARB) at stable doses for 1 month prior to enrollment, if tolerated, when ACE-I is not tolerated. Stable is defined as no more than a 100% increase or a 50% decrease in dose. If the patient is intolerant to ACE-I, ARB, or beta blockers, documented evidence must be available. In those intolerant to both ACE-I and ARB, combination therapy with hydralazine and oral nitrate should be considered. Therapeutic equivalence for ACE-I substitutions is allowed within the enrollment stability timelines. Aldosterone inhibitor therapy should be added when NYHA Class III or IV symptoms occur on standard therapy. If aldosterone inhibitor therapy is administered in Class II patients, it must be initiated and optimized prior to enrollment. Eplerenone requires dosage stability for 1 month prior to enrollment. Diuretics may be used as necessary to keep the patient euvolemic.

Exclusion

1. Inability to comply with the conditions of the protocol;
2. Inability to perform cardiopulmonary exercise test due to mechanical physical limitations
3. Presence of a transplanted tissue or organ or LVAD (or the expectation of the same within the next 12 months);
4. Planned AICD or CRT within the next 12 months unless AICD is prescribed for primary prevention
5. Pacemaker dependent patients.
6. Acute MI, CABG, PTCA, within the past 3 months
7. Chronic refractory angina or peripheral vascular pain;
8. Valvular heart disease requiring repair or replacement;
9. Need for chronic intermittent inotropic therapy;
10. Malignancy: evidence of disease within the previous 5 years;
11. Known HIV infection or immunodeficiency state;
12. Chronic active viral infection (such as hepatitis B or C);
13. Severe systemic infection: defined as patients undergoing treatment with antibiotics;
14. Active myocarditis or early postpartum cardiomyopathy (within the first 6-months of delivery);
15. Systemic corticosteroids, cytostatics and immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), DNA depleting or cytotoxic drugs taken within 4 weeks prior to study treatment;
16. Patient is pregnant, of childbearing potential and not using adequate contraceptive methods, or nursing.;
17. Patient scheduled for hospice care;
18. Any other medical, social or geographical factor, which would make it unlikely that the patient will comply with study procedures (eg. Alcohol abuse, lack of permanent residence, severe depression, disorientation, distant location and a history of non-compliance).

Contacts and Locations

Locations

United States, Texas

Methodist Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Jerry Estep, MD

The Methodist Hospital Research Institute

Investigators

• Principal Investigator: Jerry Estep, MD; Methodist Hospital DeBakey Heart & Vascular Center

More Information

• Responsible Party: Jerry Estep, MD, Sponsor-Investigator/Principal Investigator, The Methodist Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT01124136
• Other Study ID Numbers: Pro00002132; 0708-0211 ( Other Identifier: HMRI IRB )
• First Posted: May 14, 2010
• Last Update Posted: January 12, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: to be determined

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Jerry Estep, MD, The Methodist Hospital Research Institute:

Chronic Heart Failure; Neurostimulation

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases