Inhaled Nitric Oxide for Idiopathic Pulmonary Fibrosis
Recruiting in Palo Alto (17 mi)
Overseen byDenis E O'Donnell, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Dr. Denis O'Donnell
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Idiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease marked by reduced exercise capacity and activity-related breathlessness (commonly termed dyspnea). Our previous work has shown that dyspnea during exercise is associated with an increased drive to breathe (inspiratory neural drive; IND). However, little work has been done to understand the mechanisms of exertional dyspnea in patients with mild IPF. The objectives of this study are to compare the acute effects of inhaled nitric oxide to placebo on ventilatory efficiency (VE/VCO2), and IND at rest and during a standard cardiopulmonary exercise test (CPET). Twenty patients with diagnosed IPF with mild (or absent) mechanical restriction and 20 healthy age- and sex-matched controls will be recruited from a database of volunteers and from the Interstitial Lung Disease and Respirology clinics at Hotel Dieu Hospital. Participants with cardiovascular, or any other condition that contributes to dyspnea or abnormal cardiopulmonary responses to exercise will be excluded. After giving written informed consent, all participants will complete 7 visits, conducted 2 to 7 days apart. Visit 1 (screening): medical history, pulmonary function testing and a symptom limited incremental CPET. Visit 2: Standard CT examination conducted at KGH Imaging. Visit 3: assessment of resting chemoreceptor sensitivity, followed by a symptom limited incremental CPET to determine peak work rate (Wmax). Visits 4 \& 5 (run-in): familiarization to standardized constant work rate (CWR) CPET to symptom limitation at 75% Wmax. Visits 6 \& 7 (Randomized \& Blinded): CWR CPET to symptom limitation while breathing a gas mixture with either 1) 40 ppm iNO or 2) placebo \[medical grade normoxic gas, 21% oxygen\]. The proposed work has the potential to provide important physiological insights into the underlying mechanisms of heightened dyspnea, as well as examine therapeutic avenues to improve quality of life in patients with IPF.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop your current medications. However, you must be clinically stable with no changes in medication dosage or frequency in the past 6 weeks. If you are taking phosphodiesterase type 5 inhibitors, you cannot participate in the trial.
What data supports the idea that Inhaled Nitric Oxide for Idiopathic Pulmonary Fibrosis is an effective treatment?
The available research shows that inhaled nitric oxide can improve certain lung functions in patients with idiopathic pulmonary fibrosis. In one study, patients who inhaled a low dose of nitric oxide experienced a decrease in pressure in their lung arteries and a reduction in resistance to blood flow in the lungs. This suggests that inhaled nitric oxide can help improve breathing and blood flow in the lungs for these patients. However, more research is needed to confirm these findings and to compare its effectiveness to other treatments for idiopathic pulmonary fibrosis.
12345What safety data exists for inhaled nitric oxide treatment?
Inhaled nitric oxide (iNO) has been studied for its safety and efficacy in various conditions. It is used in premature infants with hypoxemia, but concerns about side effects exist. iNO affects pulmonary vasoreactivity and has known side effects, including a 'rebound' phenomenon upon withdrawal. It is also associated with renal dysfunction in patients with acute respiratory distress syndrome (ARDS). The safety profile of iNO includes potential interactions with other drugs and its chemical reactions in the lungs, which can lead to both beneficial and harmful effects.
678910Is the drug Nitric Oxide a promising treatment for Idiopathic Pulmonary Fibrosis?
Yes, Nitric Oxide shows promise as a treatment for Idiopathic Pulmonary Fibrosis. It can improve blood flow in the lungs and help with breathing by reducing pressure in the lung's blood vessels. Studies have shown that it can improve oxygen levels and reduce lung blood pressure, which are important for patients with this condition.
1451112Eligibility Criteria
Adults over 40 with a clinical diagnosis of mild Idiopathic Pulmonary Fibrosis (IPF) and no recent hospital admissions can join this trial. They must have minimal lung restriction, be clinically stable, able to perform study tasks, and not pregnant. Exclusions include significant emphysema, active heart/lung diseases other than IPF, severe obesity or underweight conditions, certain medication use, and exercise limitations due to neuromuscular issues.Inclusion Criteria
I have been diagnosed with idiopathic pulmonary fibrosis.
My lung function is mostly normal.
My health condition has been stable, with no hospital visits or medication changes in the last 6 weeks.
+3 more
Exclusion Criteria
You have a history of asthma, allergies, or nasal polyps.
Your body mass index (BMI) is either too low (less than 18.5) or too high (35.0 or more).
You have trouble breathing out air quickly.
+6 more
Participant Groups
The trial is testing the effects of inhaled nitric oxide (iNO) versus medical air placebo on breathing efficiency during rest and exercise in IPF patients compared to healthy controls. Participants will undergo several visits including pulmonary function tests, CT scans, chemoreceptor sensitivity assessments, familiarization exercises sessions followed by two blinded test sessions with either iNO or placebo.
2Treatment groups
Active Control
Placebo Group
Group I: Nitric OxideActive Control1 Intervention
Inhaled 40 ppm nitric oxide from a KINOX gas cylinder system (Air Liquid Healthcare, Montreal, Quebec, Canada; DIN 02451328).
Group II: PlaceboPlacebo Group1 Intervention
Inhaled medical grade normoxic gas (FiO2 = 0.21; DIN 02238755 Air Liquide Healthcare, Montreal, Quebec, Canada).
Nitric Oxide is already approved in United States, United States, United States for the following indications:
๐บ๐ธ Approved in United States as Inomax for:
- Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension
๐บ๐ธ Approved in United States as Noxivent for:
- Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension
๐บ๐ธ Approved in United States as GeNOsyl for:
- Hypoxic respiratory failure in term and near-term neonates with pulmonary hypertension
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Respiratory Investigation Unit, Kingston General HospitalKingston, Canada
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Who Is Running the Clinical Trial?
Dr. Denis O'DonnellLead Sponsor
Queen's UniversityLead Sponsor
Boehringer IngelheimIndustry Sponsor
References
The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis. [2019]The aim of this study was to determine whether low-dose inhalation of nitric oxide (NO) improves pulmonary haemodynamics and gas exchange in patients with stable idiopathic pulmonary fibrosis (IPF). The investigation included 10 IPF patients breathing spontaneously. Haemodynamic and blood gas parameters were measured under the following conditions: 1) breathing room air; 2) during inhalation of 2 parts per million (ppm) NO with room air; 3) whilst breathing O2 alone (1 L.min-1); and 4) during combined inhalation of 2 ppm NO and O2 (1 L.min-1). During inhalation of 2 ppm NO with room air the mean pulmonary arterial pressure (Ppa 25 +/- 3 vs 30 +/- 4 mmHg) and the pulmonary vascular resistance (PVR 529 +/- 80 vs 699 +/- 110 dyn.s.cm-5) were significantly (p
The efficacy of inhaled nitric oxide in the treatment of acute respiratory distress syndrome. An evidence-based medicine approach. [2019]Nitric oxide is an endothelial relaxing factor. When given as an inhalational agent in the acute respiratory distress syndrome (ARDS), it vasodilates well ventilated areas of lung and improves oxygenation. Nitric oxide is a highly reactive molecule with myriad biologic effects, both potentially beneficial and toxic; its use as an inhalational agent in ARDS is experimental. This article reviews the available studies of inhaled nitric oxide.
Acute exacerbation of idiopathic pulmonary fibrosis model by small amount of lipopolysaccharide in rats. [2022]Idiopathic pulmonary fibrosis, a chronic and progressive lung disease with poor prognosis, presents with acute exacerbation. Pathophysiology and treatments for this acute exacerbation, and an appropriate animal model to perform such examinations, have not established yet. We presented a rat model for assessing acute exacerbation in cases of idiopathic pulmonary fibrosis. Wistar rats were intratracheally administered bleomycin (3 mg/kg) to induce pulmonary fibrosis. After 7 days, lipopolysaccharide (0, 0.05, or 0.15 mg/kg) was administered. In the bleomycin or lipopolysaccharide group, there were almost no change in the oxygen partial pressure, arterial blood gas (PaO2), plasma nitrite/nitrate, nitric oxide synthase, and lung nitrotyrosine levels. In the bleomycin (+)/lipopolysaccharide (+) groups, these three indicators deteriorated significantly. The plasma nitrite/nitrate and PaO2 levels were significantly correlated in the bleomycin (+) groups (r = 0.758). Although lung fibrosis was not different with or without lipopolysaccharide in the bleomycin (+) groups, macrophage infiltration was marked in the bleomycin (+)/lipopolysaccharide (+) group. There were many NOS2-positive macrophages, and the PaO2 levels decrease may be induced by the nitric oxide production of macrophages in the lung. This model may mimic the pathophysiological changes in cases of acute exacerbation during idiopathic pulmonary fibrosis in humans.
Exhaled nitric oxide in interstitial lung diseases. [2015]Nitric oxide (NO) is a biomarker of nitrosative stress, which is involved in the pathogenesis of idiopathic interstitial pneumonias (IIP). This study evaluates exhaled NO levels in IIP patients and relates alveolar concentrations of NO (CalvNO) to pulmonary function test (PFT) and 6-minute walking test (6MWT) parameters. We measured fractional exhaled nitric oxide (FeNO), CalvNO and maximum conducting airway wall flux (J'awNO) in 30 healthy subjects and 30 patients with IIP (22 idiopathic pulmonary fibrosis and 8 idiopathic non-specific interstitial pneumonias). IIP patients had higher FeNO at flow rates of 50-100-150 ml/s and higher CalvNO levels than healthy controls (p
Therapeutic use of inhaled nitric oxide. [2019]Nitric oxide is a gaseous endogenous mediator of vascular dilation, neural transmission, defense against microorganisms, and inhibitor of platelet adhesion. Endothelium-derived nitric oxide is important in the maintenance of normal vascular tone in the systemic and pulmonary circulation. The discovery of a selective pulmonary vasodilator has eluded investigators for many years. Inhaled nitric oxide can be used to selectively manipulate the pulmonary vasculature and represents an important advance in pharmacologic strategies aimed at the treatment of the diseased pulmonary circulation. Indeed, preliminary studies of the therapeutic use of inhaled nitric oxide in human pulmonary hypertension and respiratory failure are yielding encouraging and exciting results. Controlled and randomized studies will be required to show improvement in patient outcome and the absence of adverse sequelae from inhaled nitric oxide therapy.
The safety and efficacy of nitric oxide therapy in premature infants. [2016]To assess the safety-efficacy balance of low-dose inhaled nitric oxide (iNO) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects.
Inhaled nitric oxide and pulmonary vasoreactivity. [2019]Inhaled nitric oxide is a ubiquitous molecule which is produced endogenously and is also found in air pollution and in cigarette smoke. After describing the chemistry of NO, we review its history from the first description in 1980 to the current clinical indications. The biosynthesis of NO, its effects on pulmonary vasoreactivity, and the administration of inhaled NO will be described. The indications, uses, and side effects of inhaled NO are discussed with an emphasis on withdrawal of NO therapy, specifically the "rebound" phenomenon. Possible drug interactions are listed. Inhaled nitric oxide is here to stay, and future studies will provide more information on its therapeutic dose, duration and potential toxicity.
The biology of nitrogen oxides in the airways. [2013]Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung. The relationship between the toxicities and the bioactivities of NOx must be understood in the context of their chemical interactions in the pulmonary microenvironment. Nitric oxide synthase (NOS) is a newly identified enzyme system active in airway epithelial cells, macrophages, neutrophils, mast cells, autonomic neurons, smooth muscle cells, fibroblasts, and endothelial cells. The chemical products of NOS in the lung vary with disease states, and are involved in pulmonary neurotransmission, host defense, and airway and vascular smooth muscle relaxation. Further, certain patients with pulmonary hypertension, adult respiratory distress syndrome and asthma may experience physiologic improvement with NOx therapy, including inhalation of nitric oxide (NO.) gas. Both endogenous and exogenous NOx react readily with oxygen, superoxide, water, nucleotides, metalloproteins, thiols, amines, and lipids to form products with biochemical actions ranging from bronchodilation and bacteriostasis (S-nitrosothiols) to cytotoxicity and pulmonary capillary leak (peroxynitrite), as well as those with frank mutagenic potential (nitrosamines). Recent discoveries demonstrating the relevance of these species to the lung have provided new insights into the pathophysiology of pulmonary disease, and they have opened a new horizon of therapeutic possibilities for pulmonary medicine.
Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study. [2022]Inhaled nitric oxide (iNO) is a rescue therapy for severe hypoxemia in patients with acute respiratory distress syndrome (ARDS). Pooled data from clinical trials have signaled a renal safety warning for iNO therapy, but the significance of these findings in daily clinical practice is unclear. We used primary data to evaluate the risk of iNO-associated renal dysfunction in patients with ARDS.
Clinical characteristics and factors associated with term and late preterm infants that do not respond to inhaled nitric oxide (iNO). [2017]Inhaled nitric oxide (iNO) is used to treat neonates with hypoxic respiratory failure (HRF). The aim of this study was to determine clinical characteristics and factors associated with non-response to iNO therapy that may assist in clinical management and weaning strategies.
Improvement in pulmonary hypertension and hypoxemia during nitric oxide inhalation in a patient with end-stage pulmonary fibrosis. [2016]A patient with severe interstitial pulmonary fibrosis, hypoxemia, pulmonary hypertension, and cor pulmonale was given inhaled nitric oxide (NO) followed by intravenous PGE1 to assess the reversibility of pulmonary hypertension. During NO inhalation, there was marked reduction in pulmonary vascular resistance, increased cardiac output, and dramatic improvement in arterial oxygenation. There was no effect on systemic vascular resistance. In contrast, intravenous PGE1 led to rapid arterial oxygen desaturation and worsened dyspnea. The beneficial responses to inhaled NO in this patient suggest that, even in severe chronic lung disease, reversible pulmonary vasoconstriction is present. Inhaled NO thus has a potential therapeutic role as a selective pulmonary vasodilator in patients with interstitial pulmonary fibrosis and cor pulmonale.
Inhaled nitric oxide selectively decreases pulmonary vascular resistance without impairing oxygenation during one-lung ventilation in patients undergoing cardiac surgery. [2013]Inhaled nitric oxide (NO), an endothelium-derived relaxing factor, is a selective pulmonary vasodilator. The authors investigated whether inhaled NO decreases pulmonary vascular resistance (PVR) while preserving hypoxic pulmonary vasoconstriction and whether it maintains or improves oxygenation in patients during one-lung ventilation.