New Narcolepsy Therapy?

Narcolepsy is a rare disorder associated with excessive sleepiness despite adequate sleep time.  A potentially highly efficacious therapy for narcolepsy, Xywav, is complicated by a difficult dosing regimen requiring twice nightly administration for optimal effect.  A new therapy in development by Avadel may provide a similar benefit in a once nightly dose.

 Avadel Pharmaceuticals plc, whose marketing application for narcolepsy drug candidate FT218 is under review by the US Food and Drug Administration (FDA), presented in eight posters at World Sleep 2022. FT218 is an investigational formulation of sodium oxybate designed to be taken once at bedtime for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy.

Data presented at World Sleep 2022 include results from a discrete choice experiment designed to characterize and quantify drivers of preferences for attributes associated with oxybate treatments for narcolepsy, with a background survey providing patient and clinician perspectives on narcolepsy disease burden, treatment approaches, and satisfaction with current narcolepsy treatment options. New post-hoc data from the completed pivotal Phase 3 REST-ON clinical trial of FT218 and interim data from the ongoing RESTORE open-label extension/switch study of FT218 was also presented.

“We know that untreated narcolepsy can have a devastating effect on patients’ quality of life and ability to function and that additional treatment options would benefit patients and clinicians. Results from the discrete choice experiment identified that the overall driver of treatment choice for oxybate therapy is once-nightly dosing,” says Anne Marie Morse, DO, director of child neurology and pediatric sleep medicine at Geisinger Medical Center at Janet Weis Children’s Hospital, in a release. “Taken together with the robust clinical data already published, along with new post-hoc analyses from the pivotal trial and interim long-term data from the ongoing open-label study….FT218 shows great potential for patient care.”

Highlights from the Poster Presentations

• The discreet choice experiment confirmed that once-nightly dosing, when compared to twice-nightly dosing, was the most important attribute driving both patient and clinician preference for overall oxybate product choice, as well as patient quality of life and reduction of patient anxiety/stress.
• Dosing frequency was also viewed as a more important attribute as compared to other attributes assessed, including sodium content.
• In the REST-ON post-hoc analyses, FT218 demonstrated improvement in subjective measures of daytime sleepiness, sleep quality, and refreshing nature of sleep as early as week 1 with the 4.5 g starting dose, with even greater improvement at week 2 soon after starting the 6 g dose compared to placebo.
• Additional post-hoc analyses, stratified by narcolepsy type, as well as concomitant stimulant use, or without stimulants, demonstrated positive results that are generally consistent with previously reported positive endpoints from REST-ON and add to the existing body of evidence for FT218.
• In the first presentation of an interim safety analysis from the ongoing RESTORE study, FT218 has generally been well tolerated, with some participants receiving therapy for more than 18 months; no new safety signals have emerged.

“In our first look at data from the interim analysis of the ongoing RESTORE study, we have affirmed that the tolerability of FT218 is in line with the well-established profile of sodium oxybate. We’re also pleased to share new results from our post-hoc analyses of the REST-ON trial that demonstrated clinically meaningful improvements with FT218 versus placebo in both subjective and objective measurements of narcolepsy symptoms, including EDS and disrupted nighttime sleep, with a dosing regimen preferred by patients and clinicians alike, consistent with our previous observations,” says Douglas Williamson, MD, chief medical officer of Avadel, in a release. “At Avadel, we believe in listening to patients to develop solutions that will have a meaningful impact on their symptoms. Our goal is to do just that for people living with narcolepsy, and we are working to bring FT218 to patients as a once-at-bedtime treatment option as quickly as possible.”

Read article here.

Sleeping for Better Cardiovascular Health in Children and Adolescents

There is a reason why personal sleep monitoring devices have proliferated in the wearable technology space.  Poor sleep health is linked to reduced cognitive function, quality of life, and cardiovascular outcomes.  Children are not immune to these complications, but they may present differently.  Obesity, hypertension, insulin resistance, and dyslipidemia have all been correlated in some form to obstructive sleep apnea or sleep disordered breathing.

Be on the lookout for the any of the following:

1) Chronic snoring, mouth breathing, pauses in breathing during sleep especially when associated with tonsillar enlargement

2) Signs of daytime sleepiness despite adequate sleep time.  Sleep needs in children vary by age, so it is important that sleep times reflect that.  Also, it is common for sleepiness to look completely different in children.  Problems with focus, attention and labile emotions and irritability in the second half of the day are quite common.

3) Special risk populations, including children that are obese, or those that have other medical disorders known to predispose to sleep apnea, such as Down Syndrome or other craniofacial abnormalities.

Any of the above warrants evaluation with a pediatric sleep specialist to discuss testing.

AHA Releases Scientific Statement on Obstructive Sleep Apnea and Cardiovascular Health in Children and Adolescents

 In a recent scientific statement, the American Heart Association (AHA) outlined evidence highlighting the effect of obstructive sleep apnea (OSA) on the cardiovascular health of children and adolescents. The full statement was published in Journal of the American Heart Association.

The AHA noted that this statement may be used to develop future guidelines in managing OSA with regard to cardiovascular disease (CVD) risk in the pediatric population.

Epidemiology and Risk Factors

Patients with OSA experience disruption during sleep caused by upper airway obstruction. In children and adolescents, the clinical presentation of the condition can vary by age, but it is generally characterized by habitual snoring, labored breathing, gasps/snorting noises, and daytime sleepiness. According to the AHA, 1% to 6% of children and adolescents have OSA. Current evidence suggests that the OSA prevalence in a pediatric population peaks between 2 and 8 years of age and corresponds to a peak in adenotonsillar hypertrophy prevalence.

Primary risk factors for OSA in the pediatric population include obesity, allergic rhinitis, upper and lower airway disease, enlarged tonsils and adenoids, low muscle tone, neuromuscular disorders, and craniofacial malformations. In addition, sickle cell disease (SCD) may be an independent risk factor for OSA. Premature birth, or birth that occurs prior to 37 weeks’ gestation, may also be associated with an increased risk for sleep-disordered breathing among children, partially because of delayed development of respiratory control.

Read article here.

Treating Sleep Apnea without CPAP

We care about the adults too.  Not all sleep apnea is the same, join us to learn about a treatment alternative.

Click HERE to register

CPAP , A Medical Aesthetic?

 

Coronary artery disease, cerebrovascular events, cardiac arrhythmias... What about fine lines and wrinkles?  Looks like we have the whole sleep apnea marketing approach wrong.

Patients With OSA Are Perceived as Younger Following Treatment With CPAP.

Yagihara F1, Lorenzi-Filho G2, Santos-Silva R3.

Abstract

BACKGROUND: 

The aim of this study was to compare the effects of CPAP treatment and placebo intervention on the facial appearance of patients with OSA.

METHODS: 

Patients with severe OSA were randomized to receive either CPAP treatment or nasal dilator (placebo) intervention for 1 month. The sequence was interposed by 15 days of washout with no treatment. Patients were evaluated by using questionnaires, polysomnography, and facial photographs at baseline and at the end of both interventions. In an electronic survey, the photographs were presented in a randomized order to 704 observers who rated the perceived age, health, attractiveness, and tiredness of the patients. Observers were unaware of the patients' conditions.

RESULTS: 

Thirty patients (age, 46 ± 9 years; 21 men; apnea-hypopnea index, 61.8 ± 26.2) were evaluated. During each intervention period, patients used CPAP 6.0 ± 1.7 h per night on 94% of the nights and the placebo intervention on 98% of the nights. After CPAP treatment, patients were rated younger (47.9 ± 3.5 years) than they appeared at baseline (53.9 ± 4.0 years) and following the placebo treatment (49.8 ± 3.7 years) (P < .001). Linear regression analysis identified that CPAP adherence, total sleep time, and percentage of total sleep time with oxyhemoglobin saturation < 90% were predictors of a decreased age rating following CPAP treatment.

CONCLUSIONS: 

Patients with severe OSA had a younger appearance following 1 month of CPAP treatment. This benefit can serve as an additional source of motivation for patients with OSA to comply with CPAP treatment and may facilitate OSA management.

Read abstract here.

Good Sleep Hygiene in Adolescents With Asthma Linked to Improved Attention

A real world comparison of this study seems to fit what we know.  Child and adolescent sleep patterns are woefully bad.  It's no surprise then that attentiveness and other quality of life factors can improve immensely when we "clean up" our sleep habits. Dr. Susarla

Adolescents with asthma who practice good sleep hygiene may experience improvements in sleep and attention span, better quality of life in school, and lower rates of dysfunction during the daytime, according to a study published in the Journal of Asthma. 

This study included 41 participants with persistent asthma (mean age, 14.83±1.28 years; 51.2% male adolescents). Measures included demographic information (sex, age, race/ethnicity, education, caregiver marital status, and family income), information on asthma, sleep hygiene via the adolescent sleep hygiene scale (ASHS), quality of sleep via the Adolescent Sleep Wake Scale (ASWS), quality of life via the Pediatric Quality of Life Index (PedsQL), and attention span via the psychomotor vigilance task (PVT).

To investigate associations among variables related to asthma, as well as between demographic features and dependent variables, Pearson product-moment correlations were used. The predictive power of sleep hygiene on sleep quality, quality of life (school-related or otherwise), and attention span was calculated using linear regressions. Because the sample size was smaller than the recommended 73 participants, effect sizes were used to interpret results. Cohen's f² effect sizes were categorized as large (0.35), medium (0.15), or small (0.02).

Read article here.

CPAP or Surveillance Device?

An unfortunate spin on an extremely useful technology that can strengthen doctor/patient relationship and improve sleep apnea outcomes when used properly.  Step off regulators!  Dr. Susarla

Last March, Tony Schmidt discovered something unsettling about the machine that helps him breathe at night. Without his knowledge, it was spying on him.

From his bedside, the device was tracking when he was using it and sending the information not just to his doctor, but to the maker of the machine, to the medical supply company that provided it and to his health insurer.

Schmidt, an information technology specialist from Carrollton, Texas, was shocked. "I had no idea they were sending my information across the wire."

Schmidt, 59, has sleep apnea, a disorder that causes worrisome breaks in his breathing at night. Like millions of people, he relies on a continuous positive airway pressure, or CPAP, machine that streams warm air into his nose while he sleeps, keeping his airway open. Without it, Schmidt would wake up hundreds of times a night; then, during the day, he'd nod off at work, sometimes while driving and even as he sat on the toilet.

"I couldn't keep a job," he said. "I couldn't stay awake." The CPAP, he said, saved his career, maybe even his life.

Read article here.

Digital Devices for Insomnia? Researchers say YES

Cognitive behavioral therapy is an intervention the incorporates coping strategies and behavioral modifications to treat a variety of conditions including insomnia.  When done properly it has been shown to be as effective as pharmacotherapy. Dr. Susarla

Digitally delivered cognitive-behavioral therapy not only improved insomnia, but also provided “around-the-clock” health, psychological, and quality-of-life improvements, according to investigators.

Compared with control subjects, patients who used a cognitive-behavioral therapy (CBT) program and associated iPhone app had small improvements in functional health and psychological well-being and large improvements in sleep-related quality of life, the investigators reported.

Those changes were mediated by a large improvement in insomnia, according to Colin A. Espie, PhD, professor of sleep medicine at the University of Oxford (England), and his colleagues.

“These findings indicate that digital CBT improves both daytime and nighttime aspects of insomnia, lending further weight to the clinical guideline recommendation of CBT as the treatment of choice for insomnia,” Dr. Espie and his colleagues reported in JAMA Psychiatry.

Their study included 1,711 adults with symptoms of insomnia that were self-reported and a score of 16 or less on the Sleep Condition Indicator (SCI), which has a range of 0-32. A total of 853 were randomized to receive digital CBT, of whom 413 completed six scheduled 20-minute sessions; an additional 276 adults completed at least one session. The control arm included 858 individuals randomized to sleep hygiene education, of whom 759 went on to receive that intervention.

Read article here.