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A Proof of Concept Study of Electrical Discharge Produced Nitric Oxide for Inhalation

Primary Purpose

Hypertension, Pulmonary

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
electrical pulsed plasma discharge synthesis of nitric oxide
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional device feasibility trial for Hypertension, Pulmonary focused on measuring Nitric Oxide

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

FIRST PART OF THE STUDY: HEALTHY VOLUNTEER STUDY (n=6 volunteers)

Inclusion Criteria:

  • Have a government photo identity card;
  • Age < 40 years old;
  • Body mass index (BMI) <28 kg/m2 and >18 kg/m2;
  • Feel well the day of nitric oxide testing;
  • Normal physical exam

Exclusion Criteria:

  • Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year;
  • Systemic disease with or without any functional limitation; including controlled hypertension and controlled diabetes without systemic effects;
  • Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin, or less than six weeks postpartum;
  • Active smoking, volunteers may be enrolled if they quit smoking for more than 1 year;
  • Excess alcohol use: more than ½ L/day of wine consumption or equivalent;
  • Any current use of a medication other than: Over-the-counter oral medications, herbal remedies, nutritional supplements, and oral contraceptives;
  • Currently enrolled in another research study.

SECOND PART OF THE STUDY: CATH-LABORATORY STUDY (n=6 cath laboratory subjects)

Inclusion criteria:

  • Have a government photo identity card;
  • Diagnosis of Pulmonary Arterial Hypertension, Group I, III, IV and V, as defined by the National Heart Lung and Blood Institute classification.
  • Known positive responder to inhaled nitric oxide
  • Wedge pressure ≤15 mmHg at baseline
  • Pulmonary arterial pressure (mean) greater than or equal to 40 mmHg
  • Scheduled Cath Lab testing for right heart catheterization to assess pulmonary vasodilator capacity

Exclusion Criteria:

  • Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year;
  • Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin, or less than six weeks postpartum;
  • Left ventricular failure for which breathing nitric oxide is contraindicated;
  • Patients with diagnosis of congenital or acquired methemoglobinemia reductase deficiency;
  • Currently enrolled in another research study.

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

electrical synthesis nitric oxide

Arm Description

Participants will breath 20 minutes of electrical pulsed plasma discharge synthesis of nitric oxide at 25 parts per million

Outcomes

Primary Outcome Measures

Oxygenation
Percent change in oxygen saturation (HbO2/totHb)
Methemoglobin
Percent change in methemoglobin levels (metHb/totHb)
Carboxyhemoglobin
Percent change in carboxyhemoglobin levels (COHb/totHb)

Secondary Outcome Measures

Pulmonary artery pressure
Change in pulmonary artery pressure (mmHg)
Cyclic guanosine monophosphate
Percent change in plasma cyclic guanosine monophosphate (measured over baseline)

Full Information

First Posted
November 21, 2014
Last Updated
February 8, 2017
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02305550
Brief Title
A Proof of Concept Study of Electrical Discharge Produced Nitric Oxide for Inhalation
Official Title
A Proof of Concept Study of Electrical Discharge Produced Nitric Oxide for Inhalation
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Study Design: This is a two-part physiological for a device feasibility. Both studies are proof of concept descriptive pilot studies. The FIRST PART is a study of healthy volunteers and the SECOND PART of patients with pulmonary hypertension at routine cardiac catheterization laboratory (CATH-LABORATORY). Volunteers and patients will be enrolled sequentially; there is no group randomization. Overall hypothesis of this device feasibility study: To test a lightweight and portable method of synthesizing therapeutic levels of inhaled nitric oxide from air by electrical pulsed discharge.
Detailed Description
Background. Inhaled nitric oxide is routinely used to treat acute pulmonary hypertension in infants, children and adults. By 2014 it has been estimate about 500,000 US patients have been treated with nitric oxide, with only the rare complication of methemoglobinemia reported at high inhaled doses. Rationale. The investigators explored novel alternative lightweight and economical methods of local nitric oxide production. In particular the investigators synthesized nitric oxide from air by an electrical pulsed plasma discharge. After 2 years of study the investigators have designed and produced a prototype of a device synthesizing nitric oxide from air with low levels of nitrogen dioxide and ozone. After completing experimentation in lambs, the investigators now plan to study nitric oxide generators in a proof of concept clinical study. Design of the study: The study is comprised of two parts: HEALTHY volunteer study, and CATH-LABORATORY study in patients. The study will be conducted at low levels of breathing nitric oxide, 25 parts per million of nitric oxide, for 20 minutes to comply with the threshold of the Environmental Protection Agency (EPA) for daily work exposure. The first portion of the study will be carried out in 6 healthy volunteers breathing 25 parts per million of nitric oxide. After this first part, the investigators will proceed to the second portion of the study and enroll 6 patients with pulmonary hypertension undergoing scheduled testing with a nitric oxide-pulmonary vasodilator response (CATH-LABORATORY study).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary
Keywords
Nitric Oxide

7. Study Design

Primary Purpose
Device Feasibility
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
electrical synthesis nitric oxide
Arm Type
Experimental
Arm Description
Participants will breath 20 minutes of electrical pulsed plasma discharge synthesis of nitric oxide at 25 parts per million
Intervention Type
Device
Intervention Name(s)
electrical pulsed plasma discharge synthesis of nitric oxide
Intervention Description
An NO generator was designed and developed by electrical pulsed plasma discharge nitric oxide from atmospheric nitrogen and oxygen. This generator has been fabricated by the investigators and it is not commercially available.
Primary Outcome Measure Information:
Title
Oxygenation
Description
Percent change in oxygen saturation (HbO2/totHb)
Time Frame
20 minutes
Title
Methemoglobin
Description
Percent change in methemoglobin levels (metHb/totHb)
Time Frame
20 minutes
Title
Carboxyhemoglobin
Description
Percent change in carboxyhemoglobin levels (COHb/totHb)
Time Frame
20 minutes
Secondary Outcome Measure Information:
Title
Pulmonary artery pressure
Description
Change in pulmonary artery pressure (mmHg)
Time Frame
20 minutes
Title
Cyclic guanosine monophosphate
Description
Percent change in plasma cyclic guanosine monophosphate (measured over baseline)
Time Frame
20 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
FIRST PART OF THE STUDY: HEALTHY VOLUNTEER STUDY (n=6 volunteers) Inclusion Criteria: Have a government photo identity card; Age < 40 years old; Body mass index (BMI) <28 kg/m2 and >18 kg/m2; Feel well the day of nitric oxide testing; Normal physical exam Exclusion Criteria: Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year; Systemic disease with or without any functional limitation; including controlled hypertension and controlled diabetes without systemic effects; Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin, or less than six weeks postpartum; Active smoking, volunteers may be enrolled if they quit smoking for more than 1 year; Excess alcohol use: more than ½ L/day of wine consumption or equivalent; Any current use of a medication other than: Over-the-counter oral medications, herbal remedies, nutritional supplements, and oral contraceptives; Currently enrolled in another research study. SECOND PART OF THE STUDY: CATH-LABORATORY STUDY (n=6 cath laboratory subjects) Inclusion criteria: Have a government photo identity card; Diagnosis of Pulmonary Arterial Hypertension, Group I, III, IV and V, as defined by the National Heart Lung and Blood Institute classification. Known positive responder to inhaled nitric oxide Wedge pressure ≤15 mmHg at baseline Pulmonary arterial pressure (mean) greater than or equal to 40 mmHg Scheduled Cath Lab testing for right heart catheterization to assess pulmonary vasodilator capacity Exclusion Criteria: Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year; Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin, or less than six weeks postpartum; Left ventricular failure for which breathing nitric oxide is contraindicated; Patients with diagnosis of congenital or acquired methemoglobinemia reductase deficiency; Currently enrolled in another research study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorenzo Berra, MD
Organizational Affiliation
MGH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22020367
Citation
Malhotra R, Hess D, Lewis GD, Bloch KD, Waxman AB, Semigran MJ. Vasoreactivity to inhaled nitric oxide with oxygen predicts long-term survival in pulmonary arterial hypertension. Pulm Circ. 2011 Apr;1(2):250-258. doi: 10.4103/2045-8932.83449.
Results Reference
background
PubMed Identifier
2040056
Citation
Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation. 1991 Jun;83(6):2038-47. doi: 10.1161/01.cir.83.6.2038. Erratum In: Circulation 1991 Nov;84(5):2212.
Results Reference
background

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A Proof of Concept Study of Electrical Discharge Produced Nitric Oxide for Inhalation

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