Novel clinical trials, treatments and diagnostic tools
Division of Pulmonary, Critical Care and Sleep Medicine - January 2018
AMBROSE CHIANG, MD
System Director of Sleep Medicine, University Hospitals Cleveland Medical Center; Clinical Associate Professor of Medicine, Case Western Reserve University School of Medicine
Sleep disorders continue to be a significant — and often underdiagnosed — problem for millions of Americans. At least 17 percent of women and 34 percent of men ages 30 to 70 have obstructive sleep apnea (OSA) or are prone to develop OSA. In addition, narcolepsy may affect up to 200,000 people in the United States.
Among children, 2 to 4 percent have OSA and 10 percent have habitual snoring. Although enlarged tonsils and adenoids are thought to play a role in these problems, newer studies have shown that signs and symptoms can improve over time or by managing nasal allergies. Older treatments such as removing tonsils and adenoids are being reevaluated for this reason.
Some of the latest research activities and advances in sleep medicine are being led by experts at University Hospitals Cleveland Medical Center.
NOVEL CLINICAL TRIALS, TREATMENTS AND DIAGNOSTIC TOOLS FOR PEDIATRIC AND ADULT PATIENTS
The PATS study, sponsored by National Institutes of Health (NIH), is examining the best treatment for children who have both snoring and mild breathing problems during sleep but do not have OSA.
It is unknown whether snoring and mild sleep disordered breathing (MSDB) are associated with behavior or other health problems in children. A common treatment for MSDB is removal of the tonsils and adenoids, but this has not been well studied. PATS will help doctors learn which treatment is best for children with MSDB.
PATS is now enrolling patients at five centers nationally, including University Hospitals Rainbow Babies & Children’s Hospital. Children ages 3 to 12 years can participate in this study if they have snoring, have not been diagnosed with OSA and have not had their tonsils removed. Carol Rosen, MD, Medical Director of the Pediatric Sleep Center at UH Rainbow Babies & Children’s Hospital and Professor of Pediatrics at Case Western Reserve University School of Medicine, and Kristie Ross, MD, Clinical Director of Pediatric Pulmonology, Allergy and Immunology at UH Rainbow Babies & Children’s Hospital and Associate Professor of Pediatrics at Case Western Reserve University School of Medicine, are principle investigators in the trial.
REST-ON CLINICAL TRIAL
XYREM® (sodium oxybate) has been available to treat narcolepsy for more than a decade. Yet the highly regulated medication requires patients to get up during the night to take a second dose.
The FDA has not yet approved Flamel’s controlled release oral suspension of sodium oxybate (FT218), which unlike XYREM, is dosed just once nightly at bedtime. To evaluate the safety and efficacy of FT218, Flamel’s study (dubbed REST-ON) is looking for patients to participate in a phase III clinical trial to compare the investigational drug with a placebo. Dr. Rosen is one of the principle investigators in this trial.
REST-ON is a now enrolling patients in multiple sleep centers worldwide. The 17-week clinical trial is open to individuals ages 16 or older with a diagnosis of narcolepsy who have excessive daytime sleepiness and cataplexy.
INSPIRE NEUROSTIMULATION THERAPY
Continuous positive airway pressure (CPAP) should still be the first line of treatment for moderate to severe sleep apnea patients – especially now that newer models and masks address comfort and leak issues, says Ambrose Chiang, MD, System Director of Sleep Medicine at University Hospitals Cleveland Medical Center and Clinical Associate Professor of Medicine at Case Western Reserve University School of Medicine. Still, many patients with sleep apnea fail to tolerate CPAP.
“About 50 percent of sleep apnea patients fail CPAP or won’t use CPAP,” Dr. Chiang says. “That is a significant failure rate.”
Those who cannot use CPAP should be reevaluated for alternative surgical or oral appliance therapy. Some will meet criteria for Inspire therapy, which uses an implantable neurostimulation device to treat OSA. Dr. Chiang notes the value of the five-year outcome data from the STAR (Stimulation Therapy for Apnea Reduction) trial.
“The Inspire implantable device consistently reduces the severity of sleep apnea,” Dr. Chiang says. “STAR found that patients averaged a 78 percent reduction in apnea-hypopnea events from baseline levels,” he says. “Inspire also improves patients’ quality of life and sleepiness scores – and patient adherence is good.”
Kingman Strohl, MD, Research Director of Sleep Medicine at UH Cleveland Medical Center, Professor of Medicine, Physiology & Biophysics, and General Medical Sciences at Case Western Reserve University School of Medicine, and a senior author of STAR trial, oversees the comprehensive Inspire program at UH.
“Dr. Strohl works closely with our ENT colleagues to offer non-CPAP therapy to our moderate to severe OSA patients who are unable to tolerate CPAP,” Dr. Chiang explains. “Our UH Dental faculty also offers dental appliance therapy to treat mild to moderate OSA patients who have failed CPAP therapy.”
HOME SLEEP APNEA TESTING
In-lab sleep study remains the gold standard for diagnosing sleep apnea, but it is not always available for all patients, Dr. Chiang says. Fortunately, home sleep apnea testing (HSAT) gives doctors another useful tool for diagnosing obstructive sleep apnea and may help turn the tide of undiagnosed sleep apnea.
HSAT costs less and typically has a shorter wait time (compared to in-lab study), and it allows users to have a more typical night’s sleep in their own homes, Dr. Chiang notes. These advantages are significant considering the magnitude of the problem and the health and safety issues associated with untreated sleep apnea.
The drawbacks? HSAT may underestimate the severity of sleep apnea and tests don’t detect total sleep times, only total recording times. “If a patient has insomnia and sleeps poorly during home sleep apnea testing,” Dr. Chiang says, “it can miss the diagnosis of sleep apnea. Therefore, a patient with negative HSAT who has a high clinical likelihood for OSA should be sent to the sleep lab for an in-lab diagnostic sleep study for further assessment.”
Also, not everyone with suspected sleep apnea is a good candidate for HSAT. For example, patients who have severe heart failure or COPD are generally not good candidates.
The newly published American Academy of Sleep Medicine’s 2017 Diagnostic Testing Clinical Practice Guideline again recommends that in-lab sleep study or an HSAT with a technically adequate device be used to diagnose OSA in uncomplicated adult patients presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA.
“We hope to offer home sleep apnea testing for many UH clinics down the road,” Dr. Chiang says. “We are in the process of developing business plans – and we hope to eventually make instruments available at UH clinics and train clinic staff. So if you identify patients with suspected sleep apnea, you can send them home with an HSAT directly from the clinic.”
For more information on the PATS clinical trial, contact Heather Rogers at 216-368-0475.
To learn more about the REST-ON clinical trial, contact Kieran McKibben at 216-286-0746 or Dr. Rosen at 216-844-3267.
For more information about Inspire therapy, contact Dr. Strohl at 216-286-7155.