By Ella Balasa
The increase in resistance rates of bacterial pathogens towards antibiotics worldwide is a major threat for those with CF. Antibiotic resistance is a term we dread. Many of us have experienced the fright and anxiety welling inside of us as weeks of oral and IV antibiotics don’t work in clearing the persistent mucus, cough, and sometimes fevers that come along with an exacerbation. The speed of development of novel antibiotics by the pharmaceutical industry has been unfortunately much slower than the emergence of resistance to many antibiotics. I, myself, have had to turn to other experimental therapy options like phage therapy, last year when no antibiotics would clear my severe exacerbation. For years, I have been hoping for new therapies that would work by different mechanisms to hinder the overgrowth of these intractable infections. Luckily, there are a few companies working on just this!
To face the unmet medical need of clearing lung infections in CF, the proposed gaseous nitric oxide, Thiolanox® inhalation therapy has been developed. Novoteris, the small pharmaceutical company developing this therapy was formed in 2013 by two respiratory therapists for the sole purpose of bringing a novel inhaled antimicrobial drug product to the market for the treatment of cystic fibrosis.
How does it kill the bacteria in the lungs? Nitric oxide establishes connections with DNA, RNA, proteins, or lipids that contain iron or sulfur to inhibit or kill target pathogens. When this inhaled gas enters a bacterial cell it disrupts the bacteria’s defense mechanisms to the point that it dies. Nitric oxide in lower concentrations is naturally produced by the body, but it is provided at a higher concentration to overwhelm and kill pathogenic bacteria. Not to worry about the potential of toxicity as it is converted to nitrites that are excreted in the urine within hours. Nitric oxide is also a mucolytic and an effective short-acting bronchodilator. This effect could contribute to the removal of secretions and maintain airway stillness. Nitric oxide has also been seen to control ciliary beat frequency in the airways.
So what is the status with clinical trials? Currently, this study is still recruiting to complete phase 2 trials which began in 2017 after seeing positive results from patients in prior phase 1 trials in 2016. Although the preliminary data isn’t publicly available, there are published studies indicating the benefits of nitric oxide. The study’s purpose is to evaluate the safety and effectiveness of inhaling nitric oxide gas for those who have been on inhaled antibiotics. In order to complete phase 2 trials, the study is in need of a few more participants!
President of Novoteris, Alex Stenzler, is hopeful not only in the benefit of nitric oxide to those with CF but that trials will be completed soon to be able to bring this drug to market as soon as possible.
“We would really appreciate help from the CF community to complete this trial since we are so close. Following our early safety trials, using our own money as well as partial funding from the Cystic Fibrosis Foundation, we started this randomized controlled trial. We are three-quarters through the trial and are hoping to recruit the remaining patients but are having difficulty finding patients locally and are willing to fly patients to the site at Children’s Hospital of Los Angeles in addition to $2160 stipend.”
Do you want to participate? You must be an adult with CF (18+) and must have taken an inhaled antibiotic for at least three months prior to beginning the study (for cycled antibiotics, participants must have completed two cycles). This study is for people who are chronically infected with Pseudomonas aeruginosa, Staphylococcus aureus or Stenotrophomonas maltophilia. Visit the Clinicaltrials.gov site for additional details and contact information. You can also call Vivica Nelson directly at 714-786-5014 or email Vivica.firstname.lastname@example.org for more information.
If you decide to volunteer and are accepted for this study, you will be randomized (selected by chance) to either be treated with the nitric oxide gas that is mixed with room air or breathe nitrogen that is mixed with room air. If you agree to be in this study, you will have some screening tests done to ensure that you are eligible to participate and you will be an outpatient at the hospital for 8 days of treatment and/or measurements.
One of our very own directors here at CF Roundtable, Mark Tremblay, participated in this study. Here is his first-hand experience!
“I decided to participate in the Novoteris nitric oxide (NO) study because based on my review and understanding of early research it showed promise to potentially be an effective antimicrobial agent with benefits for all CF patients (including those that may not benefit from modulators) and minimal side effects."
"In sum, I had confidence the study would be valuable to CF patients with minimal risk of side effects to me and I looked forward to flying cross country to go to a cool place like LA (Children's Hospital of Los Angeles) for a few weeks which was a huge break from small-town life in Poestenkill, New York. The study days where long from 8:30 am to 6:00 pm for eight days, but the stipend of $2,160 plus air transportation, hotel, meal, and parking reimbursement more than made up for it. Also, between half-hour treatment (or placebo) episodes which occurred every two hours CHLA provided me a room with WiFi and a bed which I took full advantage of by watching every season of Vampire Diaries (a delicious guilty pleasure), reading four books and of course reading and re-reading the CF Roundtable. When not at the hospital there was plenty of time to explore LA in the evenings and the free weekend between treatment days. In that time I was able to do all the hip (and nerdy) west coast things I longed to do like: visiting the oldest Farmer’s Market in the Country, shopping at the ritzy Grove, touring the Hollywood Hills, and exploring prehistoric life in North America at the Le Brea Tar Pits and Museum (okay that was pretty nerdy). The CF Foundation and Novoteris have provided all the funding for this trial which three quarters finished. They just need a few more subjects to complete the trial so if you meet the criteria (e.g., 40 and 80% FEV1), are yearning for a break from your routine and want to chill in downtown LA for a couple of weeks this is the vacation (ah study I mean) for you!”
About the author:
Ella is a director for USACFA. She is 27 years old and was born and raised in Richmond, Virginia. She was diagnosed with cystic fibrosis at 18 months old. She has a B.S. in biology and has worked in an environmental microbiology lab.
Becoming more involved within the CF community, she has received much joy from both gaining and giving support to others that face similar challenges. Her involvement in the CF community has expanded through serving on various research committees, planning virtual events, and writing to provide a scientific voice and encourage empowerment to the CF community as well as introspectively writing about the increasing hardship yet countless triumphs that come along with living a life with a chronic disease. When she is not taking care of her health, she enjoys cooking, drawing, spending time with friends, and traveling as much as she can. Follow her life experiences on Instagram @thisgirlella.